Scott G. Soltys, MD

All Publications

• Stereotactic body radiotherapy for painful spinal metastases: a decade of experience at a single institution. Journal of neurosurgery. Spine Chou, K. N., Park, D. J., Hori, Y. S., Persad, A. R., Chuang, C. F., Emrich, S. C., Ustrzynski, L., Tayag, A., Kumar, K. A., Usoz, M., Mendoza, M., Rahimy, E., Pollom, E., Soltys, S. G., Lo, C. H., Chang, S. D. 2024: 1-9

  Abstract

  This study aimed to retrospectively evaluate the efficacy of stereotactic body radiotherapy (SBRT) for pain relief in patients with painful spinal bone metastases (SBMs) and to identify key factors contributing to treatment outcomes.The authors conducted a retrospective analysis of adult patients who underwent SBRT for painful solid tumor SBMs between March 2012 and January 2023. During this period, SBRT was performed adhering to the International Spine Radiosurgery Consortium guidelines and international consensus recommendations for target volume delineation. To be included, patients needed to experience persistent pain directly associated with SBMs, warranting regular opioid treatment. Positive pain relief post-SBRT was defined by three criteria: 1) a decrease in the severity of pain; 2) reduction in opioid dosage; and 3) concurrent improvement in daily activities. The revised Tokuhashi score and Spine Instability Neoplastic Score were used to identify crucial factors influencing treatment outcomes.This study included 377 patients, covering 576 lesions across 759 vertebrae. Of these, 332 lesions showed significant pain relief within 3 months following SBRT. Lower pain relief rates were observed in patients with a revised Tokuhashi score of 0-8 or in patients with diabetes mellitus. In contrast, higher relief rates were linked to treating a single painful SBM in 1 SBRT course, and greater contouring of the involved sectors according to International Spine Radiosurgery Consortium guidelines and international consensus recommendations. The highest pain relief rate was observed in patients with prostate cancer (73.8%), whereas the lowest rate was observed in patients with hepatocellular carcinoma (36.4%). The presence of pre-SBRT vertebral fractures, the dosage and fraction of SBRT, and the use of concurrent systemic cancer therapies or antiresorptive agents, including bisphosphonates and denosumab, did not notably influence the pain relief efficacy of SBRT. Comprehensive medical records 6 months after SBRT treatment were available for only 362 lesions. The overall rate of pain relief observed was 32.6%.SBRT is an effective treatment approach for managing painful SBMs, achieving a pain relief rate of 57.6% within 3 months and maintaining a rate of 32.6% at 6 months after treatment. The transition to osteoblastic lesions may potentially improve the stability of SBMs, indicated by lower Spine Instability Neoplastic Score, which in turn could extend pain relief management.

  View details for DOI 10.3171/2024.5.SPINE231326

  View details for PubMedID 39126716

• Stereotactic Radiosurgery for Residual, Recurrent, and Metastatic Hemangiopericytomas: A Single-Institution Retrospective Experience. Neurosurgery Yoo, K. H., Park, D. J., Veeravagu, A., Persad, A., Lee, M., Marianayagam, N. J., Zamarud, A., Gu, X., Pollom, E. L., Soltys, S. G., Meola, A., Chang, S. D. 2024

  Abstract

  BACKGROUND AND OBJECTIVES: Hemangiopericytomas are infrequent vascular tumors originating from Zimmermann pericytes. The conventional treatment involves gross total resection, followed by adjuvant radiotherapy. Nevertheless, their tendency to infiltrate dural sinuses, high vascularity, and anatomic complexity pose challenges for radical resection, leading to a significant risk of recurrence. Stereotactic radiosurgery (SRS) has emerged as a promising adjuvant therapy to address these challenges. Our study provides the largest single-institutional retrospective, aiming to evaluate the effectiveness and safety of SRS as a treatment modality for residual, recurrent, and metastatic hemangiopericytomas.METHODS: From 1998 to 2023, 27 patients with 101 tumors underwent CyberKnife SRS at Stanford University Medical Center. The median age was 51 years at the time of treatment. The median follow-up period from SRS was 103 months (range: 6-250). All patients underwent upfront surgical resection. The median tumor volume was 1.5 cc. The median single-fraction equivalent dose was 19 Gy. The SRS was administered at the 76% of the median isodose line (range: 64-89).RESULTS: Of the 101 treated tumors, 24 (23.8%) progressed with a median time to recurrence of 30 months. At 10 years, the rates of local tumor control (LTC), overall survival (OS), and progression-free survival (PFS) were 74.3%, 80.8%, and 67%, respectively. In patients with metastatic lesions, the LTC rates were significantly greater when compared with those with residual or recurrent tumors. There was no significant difference between patients with residual, recurrent, and metastatic hemangiopericytomas in OS and PFS. Notably, no cases of radiation-induced adverse events were detected.CONCLUSION: SRS leads to excellent LTC, PFS, and OS at 10 years with negligible risk for adverse events. Therefore, it is an effective and safe management modality for patients with residual, recurrent, and metastatic hemangiopericytomas.

  View details for DOI 10.1227/neu.0000000000003114

  View details for PubMedID 39028180

• The Assistant Clinical Research Coordinator Program: A Pathway for Recruitment in Radiation Oncology. Advances in radiation oncology Aboytes, M., Cody, M., Laseinde, E., Hall, J., Soltys, S., Beadle, B., Kidd, E., Qian, Y., Koong, A. C., Chang, D., Le, Q., Pollom, E. L. 2024; 9 (7): 101504

  Abstract

  Purpose: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology.Methods and Materials: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution's clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to assess their program experience using a Likert scale.Results: From 2005 to 2023, the ACRC program paired 73 ACRCs with faculty. Most faculty (68%) are currently supported by ACRCs. In 2023, 113 applications were received for 4 positions. ACRCs have contributed to research publications (293 as coauthors and 43 as first authors) and taken on leadership roles in the department. Most program alumni have attended medical school (34 of 64 program graduates; 53%). Eight have chosen to specialize in radiation oncology (13%; 2 applying into radiation oncology, 1 in residency, and 5 attendings). Of the 25% of alumni who responded to our survey, 77% responded that the mentorship provided by the ACRC program was very or extremely effective in guiding their academic development. All respondents rated the research opportunities as good or excellent, and 77% rated the clinical experience opportunities as good or excellent. Most (77%) reported that the ACRC program had substantial or significant influence on their choice of career path.Conclusions: The ACRC program provides an opportunity to address recruitment challenges in radiation oncology by offering early exposure to the field, clinical research skills, and mentorship. With the strong interest in our job posting this year, there is potential to expand this program to other institutions.

  View details for DOI 10.1016/j.adro.2024.101504

  View details for PubMedID 38846487

• The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations. Journal of clinical medicine Yoo, K. H., Marianayagam, N. J., Park, D. J., Zamarud, A., Gu, X., Pollom, E., Soltys, S. G., Meola, A., Chang, S. D. 2024; 13 (12)

  Abstract

  Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3-18) and two adult patients (ages 19-75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusions: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.

  View details for DOI 10.3390/jcm13123592

  View details for PubMedID 38930121

• A phase II study of plerixafor combined with whole brain radiation therapy (WBRT) for patients with newly diagnosed glioblastoma Cao, T., Gu, Y., Yagmurlu, B., Yerraballa, H., Bertrand, S., Naya, L., Miller, K., Iv, M., Soltys, S. G., Patel, C. B., Nagpal, S., Thomas, R., Brown, M., Recht, L. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557400433

• Multi-institutional study of reirradiation for recurrent high grade glioma Helis, C. A., Zarabi, H., Russell, G., LeCompte, M., Liu, W., Hattangadi-Gluth, J., Halasz, L., Soltys, S. G., Braunstein, S. E., Wang, T. C., Shi, W., Shen, C., Mignano, J., Masters, A., Kleinberg, L., Huang, J., Hopper, A., Barbour, A., Jeyapalan, S. A., Chan, M. D. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557400423

• Primary Stereotactic Body Radiotherapy for Spinal Bone Metastases From Lung Adenocarcinoma. Clinical lung cancer Chou, K. N., Park, D. J., Hori, Y. S., Persad, A. R., Chuang, C., Emrish, S. C., Ustrzynski, L., Tayag, A., Kumar, K., Usoz, M., Mendoza, M., Rahimy, E., Pollom, E., Soltys, S. G., Lai, S. W., Chang, S. D. 2024

  Abstract

  This study aimed to assess the results of primary stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM) originating from lung adenocarcinoma (ADC). We considered the revised Tokuhashi score (rTS), Spinal Instability Neoplastic Score (SINS), and genetic characteristics.We examined adult patients with lung ADC who underwent primary SBRT (using the CyberKnife System) for SBM between March 2012 and January 2023.We analyzed data from 99 patients, covering 152 SBM across 194 vertebrae. The overall local control (LC) rate was 77.6% for SBM from lung ADC, with a LC rate of 90.7% at 1 year. The median period for local progression (LP) occurrence was recorded at 10.0 (3-52) months. Additionally, Asian patients demonstrated higher LC rates than White patients. Utilizing the rTS and SINS as predictive tools, we revealed that a poor survival prognosis and an unstable spinal structure were associated with increased rates of LP. Furthermore, the presence of osteolytic bone destructions and pain complaints were significantly correlated with the occurrence of LP. In the cohort of this study, 108 SBM underwent analysis to determine the expression levels of programmed cell death ligand 1 (PD-L1). Additionally, within this group, 60 showed mutations in the epidermal growth factor receptor (EGFR) alongside PD-L1 expression. Nevertheless, these genetic differences did not result in statistically significant differences in the LC rate.The one-year LC rate for primary SBRT targeting SBM from lung ADC stood at 90.7%, particularly with the use of the CyberKnife System. Patients achieving LC exhibited significantly longer survival times compared to those with LP.

  View details for DOI 10.1016/j.cllc.2024.05.007

  View details for PubMedID 38897849

• Stereotactic Radiosurgery for Ependymoma in Pediatric and Adult Patients: A Single-Institution Experience. Neurosurgery Yoo, K. H., Marianayagam, N. J., Park, D. J., Persad, A., Zamarud, A., Shaghaghian, E., Tayag, A., Ustrzynski, L., Emrich, S. C., Gu, X., Ho, Q. A., Soltys, S. G., Meola, A., Chang, S. D. 2024

  Abstract

  Ependymoma is commonly classified as World Health Organization grade 2 with the anaplastic variant categorized as grade 3. Incomplete resection or anaplastic features can result in unfavorable outcomes. Stereotactic radiosurgery (SRS) provides a minimally invasive approach for recurrent ependymomas. Our study investigates the efficacy and safety of SRS for grade 2 and 3 ependymomas in pediatric and adult populations.We conducted a retrospective analysis on 34 patients with 75 ependymomas after CyberKnife SRS between 1998 and 2023. Fourteen were pediatric (3-18 years), and 20 were adult (19-75 years) patients. The median age was 21 years, and the median tumor volume was 0.64 cc. The median single-fraction equivalent dose was 16.6 Gy, with SRS administered at 77% of the median isodose line.After a median follow-up of 42.7 months (range: 3.8-438.3), 22.7% of ependymomas progressed. The 5-year local tumor control rate was 78.1%, varying between 59.6% and 90.2% for children and adults, with grade 2 at 85.9% compared with 58.5% for grade 3 tumors. The 5-year overall survival rate was 73.6%, notably higher in adults (94.7%) than in children (41%), and 100% for grade 2 but decreased to 35.9% for grade 3 patients. The 5-year progression-free survival rate was 68.5%, with 78.3% and 49.2% for adults and children, respectively, and a favorable 88.8% for grade 2, contrasting with 32.6% for grade 3 patients. Symptom improvement was observed in 85.3% of patients. Adverse radiation effects occurred in 21.4% of pediatric patients.Our study supports SRS as a viable modality for pediatric and adult patients with grade 2 and 3 ependymomas. Despite lower local tumor control in pediatric and grade 3 cases, integrating SRS holds promise for improved outcomes. Emphasizing careful patient selection, personalized treatment planning, and long-term follow-up is crucial for optimal neurosurgical outcomes.

  View details for DOI 10.1227/neu.0000000000002979

  View details for PubMedID 38785440

• CyberKnife stereotactic radiosurgery for extramedullary plasmacytoma in the external auditory canal: illustrative case. Journal of neurosurgery. Case lessons Patil, S., Shaghaghian, E., Yuan, L., Shah, A., Marianayagam, N. J., Park, D. J., Soltys, S. G., Veeravagu, A., Gibbs, I. C., Li, G., Chang, S. D. 2024; 7 (19)

  Abstract

  Plasmacytoma, a rare plasma cell disorder, often presents as a solitary or multiple tumors within the bone marrow or soft tissues, typically associated with multiple myeloma. Extramedullary plasmacytomas (EMPs), particularly those located in the external auditory canal (EAC), are exceedingly rare and pose significant treatment challenges given their location, anatomical complexity, and high risk of recurrence.The authors report the case of a 72-year-old male with a history of multiple myeloma, presenting with recurrent left EAC plasmacytoma. After initial conventional radiotherapy for the lesion, a recurrence was documented in 7 years. The patient subsequently underwent stereotactic radiosurgery, which proved successful, leading to complete resolution of the lesion without any long-term adverse effects or radiation-related complications over a 45-month period.This case is a unique instance of utilizing stereotactic radiosurgery for recurrent EMP in the EAC, highlighting its potential as an effective approach in managing complex plasmacytomas.

  View details for DOI 10.3171/CASE2479

  View details for PubMedID 38710109

  View details for PubMedCentralID PMC11076403

• Where Does Auto-Segmentation for Brain Metastases Radiosurgery Stand Today? Bioengineering (Basel, Switzerland) Kim, M., Wang, J. Y., Lu, W., Jiang, H., Stojadinovic, S., Wardak, Z., Dan, T., Timmerman, R., Wang, L., Chuang, C., Szalkowski, G., Liu, L., Pollom, E., Rahimy, E., Soltys, S., Chen, M., Gu, X. 2024; 11 (5)

  Abstract

  Detection and segmentation of brain metastases (BMs) play a pivotal role in diagnosis, treatment planning, and follow-up evaluations for effective BM management. Given the rising prevalence of BM cases and its predominantly multiple onsets, automated segmentation is becoming necessary in stereotactic radiosurgery. It not only alleviates the clinician's manual workload and improves clinical workflow efficiency but also ensures treatment safety, ultimately improving patient care. Recent strides in machine learning, particularly in deep learning (DL), have revolutionized medical image segmentation, achieving state-of-the-art results. This review aims to analyze auto-segmentation strategies, characterize the utilized data, and assess the performance of cutting-edge BM segmentation methodologies. Additionally, we delve into the challenges confronting BM segmentation and share insights gleaned from our algorithmic and clinical implementation experiences.

  View details for DOI 10.3390/bioengineering11050454

  View details for PubMedID 38790322

• Treatment of Refractory Bipolar Depression With Stereotactic Radiosurgery Targeting the Subgenual Cingulate Cortex. Cureus Solvason, H. B., Marianayagam, N. J., Soltys, S. G., Schatzberg, A. F., DeBattista, C., Ketter, T., Wang, P., Chang, S. D., Spiegel, D., Adler, J. R. 2024; 16 (4): e57904

  Abstract

  Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.

  View details for DOI 10.7759/cureus.57904

  View details for PubMedID 38725772

  View details for PubMedCentralID PMC11079710

• Executive Summary of the American Radium Society Appropriate Use Criteria for Brain Metastases in EGFR-mutated and ALK-fusion Non-Small Cell Lung Cancer. Neuro-oncology Nagpal, S., Milano, M. T., Chiang, V. L., Soltys, S. G., Brackett, A., Halasz, L. M., Garg, A. K., Sahgal, A., Ahluwalia, M. S., Tom, M. C., Palmer, J. D., Knisley, J. P., Chao, S. T., Gephart, M. H., Wang, T. J., Lo, S. S., Chang, E. L. 2024

  Abstract

  The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy (RT).The panel developed three key questions to guide systematic review: can radiotherapy be deferred in patients receiving EGFR or ALK TKIs at 1) diagnosis or 2) recurrence? Should TKI be administered concurrently with RT (3)? Two literature searches were performed (May 2019 and December 2023). The panel developed 8 model cases and voted on treatment options using a 9-point scale, with 1-3, 4-6 and 7-9 corresponding to usually not appropriate, may be appropriate, and usually appropriate (respectively), per the UCLA/RAND Appropriateness Method.Consensus was achieved in only 4 treatment scenarios, all consistent with existing ARS-AUC guidelines for multiple BrM. The panel did not reach consensus that RT can be appropriately deferred in patients with BrM receiving CNS penetrant ALK or EGFR TKIs, though median scores indicated deferral may be appropriate under most circumstances. Whole brain RT with concurrent TKI generated broad disagreement except in cases with 2-4 BrM, where it was considered usually not appropriate.We identified no definitive studies dictating optimal sequencing of TKIs and RT for EGFRm and ALK+ BrM. Until such studies are completed, the committee hopes these cases guide decision-making in this complex clinical space.

  View details for DOI 10.1093/neuonc/noae041

  View details for PubMedID 38459978

• Evolving concepts in margin strategies and adaptive radiotherapy for glioblastoma: A new future is on the horizon. Neuro-oncology Tseng, C. L., Zeng, K. L., Mellon, E. A., Soltys, S. G., Ruschin, M., Lau, A. Z., Lutsik, N. S., Chan, R. W., Detsky, J., Stewart, J., Maralani, P. J., Sahgal, A. 2024; 26 (Supplement_1): S3-S16

  Abstract

  Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from 1.5 to 3.0 cm beyond the GTV remains the standard of care. Over the past 15 years, the incorporation of standard and functional MRI sequences into the treatment workflow has become a routine practice with increasing adoption of MR simulators, and new integrated MR-Linac technologies allowing for daily pre-, intra- and post-treatment MR imaging. There is now unprecedented ability to understand the tumor dynamics and biology of GBM during RT, and safe CTV margin reduction is being investigated with the goal of improving the therapeutic ratio. The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities associated with both online and offline adaptive workflows. Lastly, opportunities to biologically guide adaptive RT using non-invasive imaging biomarkers and the potential to define appropriate volumes for dose modification will be discussed.

  View details for DOI 10.1093/neuonc/noad258

  View details for PubMedID 38437669

  View details for PubMedCentralID PMC10911794

• Surgery and stereotactic radiosurgery for spinal leiomyosarcoma: a single-institution retrospective series and systematic review. Journal of neurosurgery. Spine Zamarud, A., Marianayagam, N. J., Sekar, V., Testa, S., Park, D. J., Yener, U., McCleary, T. L., Yoo, K. H., Emrich, S., Tayag, A., Ustrzynski, L., Pollom, E., Soltys, S., Wang, L., Charville, G., Ganjoo, K., Chang, S. D., Meola, A. 2023: 1-13

  Abstract

  Leiomyosarcoma (LMS) is a rare, aggressive soft-tissue sarcoma that seldom spreads to the bone. The spine can be either the site of LMS osseous metastases or the primary tumor site. The optimal treatment option for spinal LMS is still unclear. The authors present a cohort of patients with spinal LMS treated with either upfront surgery or upfront CyberKnife stereotactic radiosurgery (SRS).The authors retrospectively studied the clinical and radiological outcomes of 17 patients with spinal LMS treated at their institution between 2004 and 2020. Either surgery or SRS was used as the upfront treatment. The clinical and radiological outcomes were assessed. A systematic review of the literature was also conducted.Of the 17 patients (20 spinal lesions), 12 (70.6%) were female. The median patient age was 61 years (range 41-80 years). Ten patients had upfront surgery for their spinal lesions, and 7 had upfront CyberKnife radiosurgery. The median follow-up was 11 months (range 0.3-130 months). The median overall survival (OS) for the entire cohort was 13 months (range 0.3-97 months). In subgroup analysis, the median OS was lower for the surgical group (13 months, range 0.3-50 months), while the median OS for the SRS group was 15 months (range 5-97 months) (p = 0.5). Forty percent (n = 4) of those treated with surgery presented with local recurrence at a median of 6.7 months (range 0.3-36 months), while only 14% (n = 1) of those treated with CyberKnife radiosurgery had local recurrence after 5 months. Local tumor control (LTC) rates at the 6-, 12-, and 18-month follow-ups were 72%, 58%, and 43%, respectively, for the SRS group and 40%, 30%, and 20%, respectively, for the surgery group (p < 0.05). The literature review included 35 papers with 70 patients harboring spinal LMS; only 2 patients were treated with SRS. The literature review confirms the clinical and radiological outcomes of the surgical group, while data on SRS are anecdotal.The authors present the largest series in the literature of spinal LMS and the first on SRS for spinal LMS. This study shows that LTC is statistically significantly better in patients receiving upfront SRS instead of surgery. The OS does not appear different between the two groups.

  View details for DOI 10.3171/2023.10.SPINE23666

  View details for PubMedID 38157539

• Impact of language barriers and use of interpreters on hope among patients with Central Nervous System Malignancies and Bone Metastases. International journal of radiation oncology, biology, physics Hui, C., Hall, J., Fang, Z., Lefebvre, S., Hayden-Gephart, M., Li, G., Meola, A., Nagpal, S., Soltys, S., Pollom, E. 2023

  Abstract

  PURPOSE: Hope is important in serious illnesses, as it has been linked to patient quality of life. We aimed to determine factors associated with lower hope scores among patients with central nervous system (CNS) disease or bone metastases.METHODS: The Adult Dispositional Hope Scale (AHS) is a 12-item questionnaire that measures hope through two qualities: agency (goal-directed energy) and pathways (plan to meet goals). Total scores range from 8 to 64, with higher scores reflecting higher agency and pathways thinking. We prospectively collected scores from patients seen in two radiation oncology clinics at our institution from 10/2022 to 4/2023. The method of least squares to fit general linear models and Pearson's correlation coefficients (PCC) was used to determine relationships between AHS score and socioeconomic and disease factors.RESULTS: Of the 197 patients who responded, median age was 60.5 years (range 16.9-92.5 years), most patients were male (60.9%), white (59.4%), and had malignant disease (59.4%). Median overall AHS score was 54 (range 8-64), and median pathway and agency thinking scores were 27 (range 4-32) and 27 (range 4-32), respectively. Patients who needed an interpreter compared to those who did not had significantly lower overall AHS scores (mean score 45.4 versus 51.2, respectively; p=0.0493) and pathway thinking scores (mean score 21.5 versus 25.7, respectively; p=0.0085), and patients with poorer performance status had significantly worse overall AHS scores (PCC=-0.2703, p=0.0003).CONCLUSION: Patients with CNS disease or bone metastases requiring the use of an interpreter had lower AHS scores, highlighting the possible association of language barriers to hope. Addressing patient language barriers and further studies on the possible association of language barriers to hope may improve hope, quality of life and outcomes among these patients.

  View details for DOI 10.1016/j.ijrobp.2023.11.056

  View details for PubMedID 38056777

• Spinal metastases of pineal region glioblastoma with primitive neuroectodermal features highlighting the importance of molecular diagnoses: illustrative case. Journal of neurosurgery. Case lessons Shah, A., Marianayagam, N. J., Zamarud, A., Park, D. J., Persad, A. R., Soltys, S. G., Chang, S. D., Veeravagu, A. 2023; 6 (20)

  Abstract

  Glioblastoma (GBM) is the most common primary brain tumor with poor patient prognosis. Spinal leptomeningeal metastasis has been rarely reported, with long intervals between the initial discovery of the primary tumor in the brain and eventual spine metastasis.Here, the authors present the case of a 51-year-old male presenting with 7 days of severe headache, nausea, and vomiting. Magnetic resonance imaging of the brain and spine demonstrated a contrast-enhancing mass in the pineal region, along with spinal metastases to T8, T12, and L5. Initial frozen-section diagnosis led to the treatment strategy for medulloblastoma, but further molecular analysis revealed characteristics of isocitrate dehydrogenase-wild type, grade 4 GBM.Glioblastoma has the potential to show metastatic spread at the time of diagnosis. Spinal imaging should be considered in patients with clinical suspicion of leptomeningeal spread. Furthermore, molecular analysis should be confirmed following pathological diagnosis to fine-tune treatment strategies.

  View details for DOI 10.3171/CASE23536

  View details for PubMedID 37956418

• STEREOTACTIC RADIOSURGERY FOR RESIDUAL, RECURRENT, AND METASTATIC HEMANGIOPERICYTOMAS: A SINGLE INSTITUTION EXPERIENCE Yoo, K., Park, D., Veeravagu, A., Lee, M., Marianayagam, N., Zamarud, A., Gu, X., Pollom, E., Soltys, S., Chang, S., Meola, A. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001115245400225

• STEREOTACTIC RADIOSURGERY FOR CYSTIC AND SOLID INTRACRANIAL HEMANGIOBLASTOMAS: A SINGLE-INSTITUTION RETROSPECTIVE SERIES Yoo, K., Park, D., Marianayagam, N., Pollom, E., Soltys, S., Meola, A., Chang, S. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001115245400236

• Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series. Neurosurgery Yoo, K. H., Park, D. J., Marianayagam, N. J., Gu, X., Pollom, E. L., Soltys, S. G., Chang, S. D., Meola, A. 2023

  Abstract

  Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution.We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line.At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection.SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.

  View details for DOI 10.1227/neu.0000000000002728

  View details for PubMedID 37967154

• Role of Fractionation in Local Control of Spinal Metastases Treated with Stereotactic Radiosurgery. International journal of radiation oncology, biology, physics Klebaner, D., Pollom, E., Mendoza, M., Kumar, K. A., Gibbs, I. C., Chang, S. D., Hancock, S. L., Soltys, S. G. 2023; 117 (2S): e117-e118

  Abstract

  Optimal fractionation of spinal stereotactic radiosurgery (SRS) for spine metastases remains unknown. Retrospective data suggest decreased local failure (LF) with fractionated SRS of brain metastases. We evaluated our institutional outcomes of spinal SRS with the hypothesis that fractionation improves the rate of local failure compared to single-fraction treatment.This IRB-approved, retrospective analysis included patients with spine metastases treated with spinal SRS between October 2002 and November 2014 with evaluable follow-up imaging and no prior irradiation to the given segment. The exposure of interest was single- or multi-fraction SRS with a primary endpoint of the cumulative incidence of LF with death as a competing risk. We assessed bivariate associations between fractionation and single-fraction equivalent dose (SFED in Gy10) as well as high-risk features, defined as epidural extension (Bilsky Scale), paraspinous extension, and gastrointestinal (GI) vs non-GI primary. We calculated the rates of LF and vertebral body compression fracture (VCF) at 1-year, and assessed LF by fractionation when limited only to courses receiving SFED>18 Gy. We analyzed the association between fractionation and LF using subdistribution hazard ratios (SHR) estimated from competing risks regression with death as a competing risk and adjusting for lesion-specific characteristics as well as SFED to determine contribution of these variables to the estimated effect of fraction number on LF. We calculated relative attenuation for the contribution of SFED to this association, defined as [SHRfractions-SHRfractions+SFED] ÷ [SHRSFED-1].In 293 patients with 516 spinal segments, lesions treated with single fraction compared to multi-fraction SRS had less epidural (19% vs 36%, p<0.001) and paraspinous (20% vs 35%, p<0.001) extension, more GI histology (17% vs 10%, p = 0.039), received a higher mean SFED (18.3 Gy vs. 16.6 Gy, p<0.001), and had a lower 1-year LF (8% vs 14%, p = 0.02), with no difference in VCF (7% vs. 5%, p = 0.38). After adjusting for high-risk features, single fraction SRS was associated with lower LF (SHR = 0.45, 95% CI 0.24-0.84, p = 0.02). After adjustment for SFED, this association of fractionation was attenuated by 53% and became insignificant (SHR = 0.78, 95% CI 0.44-1.37, p = 0.38). Overall, 1-year LF for SFED>18 Gy was 6% compared to 15% for <18 Gy (p<0.001). When limited to courses with SFED>18 Gy (n = 261), single fraction SRS had no improvement in 1-year LF compared to multi-fraction (6.6% vs 4.6%, p = 0.77).Single fraction SRS was associated with better local control compared to multi-fraction; however, much of this association was attenuated by SFED but not by high-risk features of treated lesions. To clarify the role of fractionation, we have initiated a prospective, randomized trial of single vs. multi-fraction SRS utilizing the same SFED.

  View details for DOI 10.1016/j.ijrobp.2023.06.903

  View details for PubMedID 37784661

• Overall Survival Prediction in Stereotactic Radiosurgery Patients with Glioblastoma Via a Deep-Learning Approach. International journal of radiation oncology, biology, physics Yang, Z., Zamarud, A., Marianayagam, N., Park, D., Yener, U., Soltys, S. G., Chang, S. D., Meola, A., Lu, W., Gu, X. 2023; 117 (2S): e159

  Abstract

  PURPOSE/OBJECTIVE(S): Accurate and automated early survival prediction is critical for glioblastoma (GBM) patients as their poor prognosis requires timely treatment decision-making. We have developed a deep learning (DL)-based GBM overall survival (OS) prediction model based on a multi-institutional public dataset using only pre-operative basic structural multi-parametric magnetic resonance images (MRIs). The purpose of this study is to evaluate this DL-based OS prediction model with an institutional stereotactic radiosurgery (SRS) clinical trial dataset.MATERIALS/METHODS: The task of this study is to classify GBM patients into 3 OS classes: long-survivors (>15 months), mid-survivors (between 10 and 15 months) and short-survivors (< 10 months). The proposed OS prediction model is an ensemble of a ResNet-based classifier and a K-NN classifier. The ResNet-based classifier is trained in a Siamese fashion to explore inter-class differences. During testing, training sample features are implemented with a K-NN classifier to ensemble with the ResNet-based classifier. A public dataset from Medical Image Computing and Computer Assisted Intervention (MICCAI) Brain Tumor Segmentation (BraTS) challenge 2020 (235 patients) were used for model establishing and initial validation. Then the validated model was evaluated on 19 GBM patients from an institutional SRS clinical trial. Each data entry consists of pre-operative basic structural multi-parametric MRIs and survival days, as well as patient ages for BraTS data and basic clinical characteristics for institutional data. GBM sub-regions, including contrast-enhancing tumor, peri-tumoral edema, and necrotic/non-enhancing tumor core, were segmented in the multi-parametric MRIs by an in-house DL model for both datasets. The OS prediction model was trained on 90% of the segmented BraTS data and validated on the rest 10%, then further evaluated on the institutional data. The model performance was assessed by prediction accuracy (ACC) and the area under the curve (AUC).RESULTS: For this 3-class OS classification task, our DL-based prediction model achieved an ACC of 65.22% and an AUC of 0.81 on the BraTS dataset compared with the top-ranked result from the BraTS challenge 2020 (Rank 1st: ACC 61.7%), and an ACC of 52.63% and an AUC of 0.69 on the institutional dataset. Further analysis of the institutional dataset found that the predicted OS class had a statistically significant correlation with treatment volume (p = 0.012) and age (p = 0.006), which matches the analysis that the patients' ground truth OS class is statistical significantly correlated with treatment volume (p = 0.045).CONCLUSION: Our DL-based OS prediction model for GBM using basic structural multi-parametric pre-operative MRIs has demonstrated promising performance in both public and institutional dataset with minimal manual processing requirements. This OS prediction model can be potentially applied to assist timely clinical decision-making.

  View details for DOI 10.1016/j.ijrobp.2023.06.988

  View details for PubMedID 37784752

• Impact of Employment and Insurance Status on Hope Among Patients Treated within Radiation Oncology. International journal of radiation oncology, biology, physics Hui, C., Hall, J. C., Snyder, J. M., Lefebvre, S., Soltys, S. G., Pollom, E. 2023; 117 (2S): e237-e238

  Abstract

  PURPOSE/OBJECTIVE(S): Hope is important in serious illnesses including cancer, as it has been linked to patient well-being and quality of life. We assessed hope among patients seen in radiation oncology and aimed to determine associated socioeconomic and disease factors. We hypothesized that patients who may have less resources to cope with their illness would have lower hope scores.MATERIALS/METHODS: The Adult Dispositional Hope Scale (AHS) is a questionnaire that aims to measures an individual's determination to accomplish goals and planning strategies to accomplish goals. We prospectively collected AHS survey scores from patients with benign or malignant disease seen in 2 radiation oncology clinics at our institution from 10/2022 to 1/2023. The AHS survey contains 12 items to measure hope through two qualities: agency (goal-directed energy) and pathways (plan to meet goals). Each item is answered using an 8-point scale. There are 4 items each for the Agency and Pathway subscales with 4 filler items for total scores ranging from 8 to 64, with higher scores reflecting higher agency and pathways thinking. Kruskal-Wallis H test and Kendall's Tau Rank Correlation were used to determine differences between categorical and continuous variables on AHS scores, respectively.RESULTS: We included 228 patients with a median age of 62 years (range 16.9-92.6). Half were male (51%), 56% were white, and 77% had malignant disease. The primary disease subsite was CNS, GI and other in 76 (34%), 70 (31%), and 81 (36%) patients, respectively. Of patients with known occupation and insurance information, 32 (14%), 67 (29%), and 49 (22%) were not employed, employed, and retired, respectively, and 115 (50%), 85 (37%), and 20 (9%) had private insurance, Medicare, and Medical, respectively. Median agency, pathway, and total hope scores were 27 (interquartile range [IQR] 24-29), 28 (IQR 24-30), and 55 (IQR 48-58), respectively. Higher total hope scores were associated with being employed (p = 0.02), having private insurance (p<0.02), and higher ECOG scores (p<0.01). After excluding those who are not employed because they are retired (n = 99), lack of employment was significantly associated with hope (p<0.01). Characteristics such as race/ethnicity, gender, marital status, pain, symptoms from disease, malignant or benign disease, stage of disease, and treatment modalities were not associated with AHS scores.CONCLUSION: In our study, patients with non-private insurance and being currently unemployed had lower AHS scores. The lower hope scores suggest that these patients may have fewer resources to cope with their treatments and diagnoses and may benefit from further inquiry about the need to mitigate cancer-related financial burden to improve hope levels. Further studies are needed to evaluate whether financial toxicity, which has been shown to negatively impact patient outcomes, is correlated to coping and hope.

  View details for DOI 10.1016/j.ijrobp.2023.06.1161

  View details for PubMedID 37784941

• Multi-Institutional Report of Re-Irradiation for Recurrent High-Grade Glioma. International journal of radiation oncology, biology, physics Zarabi, H., Helis, C. A., Russell, G., Huang, J., Liu, W., Soltys, S. G., Mendoza, M., Braunstein, S. E., Salans, M. A., Wang, T. J., Gallitto, M., Shi, W., Cappelli, L., Shen, C., Young, M. D., Mignano, J. E., Halasz, L. M., Barbour, A. B., Masters, A. H., Chan, M. D. 2023; 117 (2S): S85-S86

  Abstract

  PURPOSE/OBJECTIVE(S): Significant heterogeneity exists with regards to prior published reports of re-irradiation (re-RT) in patients with recurrent high grade glioma (HGG). A multi-institutional database of 10 academic centers across the United States was created to analyze prognostic outcomes for re-RT for recurrent HGG, which included WHO Grade III and Grade IV tumors.MATERIALS/METHODS: Patients with HGG who had initially received standard radiotherapy (RT) and were subsequently treated with a course of re-RT at recurrence were included in the study. Factors assessed to delineate a significant association with overall survival (OS) and toxicity included age, KPS, number of relapses, dose, use of bevacizumab (BEV) or temozolomide (TMZ), time from prior RT, histology, RT target, re-RT target> 5cm and extent of resection, and MGMT methylation status. The Kaplan-Meier Method was used to estimate OS. Cox proportional hazards regression models were used to identify factors associated with OS. Toxicity outcomes were assessed using logistic regression. Significance was assumed if p<0.05. Data management and decision management software were used for all analyses.RESULTS: Between 2001 and 2022, 280 patients from 10 academic institutions were treated with re-RT for diagnosis of recurrent HGG. 133 patients (71.1%) had a histologic glioblastoma (GBM) at the time of re-RT, with the remainder having Grade 3 gliomas. Median dose delivered at re-RT was 47 Gy BED10 (IQR 47 - 53 Gy BED10), with the most common regimen being 35 Gy in 10 fractions. 83 patients (56%) had GTV greater than 5 cm treated with re-RT. 183 patients (79%) received concurrent systemic therapy, including 95 (41%) who received concurrent TMZ and 86 (45%) who received concurrent BEV. Median OS for the entire cohort was 10 months. Increasing dose at re-RT was associated with improved OS (OR 0.80 95% CI 0.67-0.95, p = 0.10 per 10 Gy BED10), as was dose greater than 47 Gy BED10, which is equivalent to 35 Gy in 10 fractions (OR 0.70, 95% CI 0.54-0.91). Concurrent TMZ was also associated with improved OS (OR 0.68, 95% CI 0.46-0.83, p < 0.01). 32/143 (22%) patients evaluable for toxicity experienced Grade 2 or greater adverse radiation effect (ARE). Use of BEV was associated with decreased toxicity (OR 0.45, 95% CI 0.21-0.98, p = 0.05). Dose at re-RT (OR 1.07 per 10 Gy BED10, p = 0.78), a GTV > 5cm (OR 1.39, p = 0.44), and the use of concurrent TMZ (OR 1.90, p = 0.10) were not associated with Grade 2 or greater ARE.CONCLUSION: Higher dose of re-RT and use of concurrent TMZ led to improved OS in recurrent HGG patients without an associated increased rate of ARE. Use of BEV decreased the likelihood of Grade 2 or greater ARE in the re-RT setting for these recurrent HGG patients.

  View details for DOI 10.1016/j.ijrobp.2023.06.408

  View details for PubMedID 37784590

• Practical Guideline for Prevention of Patchy Hair Loss following CyberKnife Stereotactic Radiosurgery for Calvarial or Scalp Tumors: Retrospective Analysis of a Single Institution Experience. Stereotactic and functional neurosurgery Park, D. J., Marianayagam, N. J., Yener, U., Tayag, A., Ustrzynski, L., Emrich, S. C., Pollom, E., Soltys, S., Meola, A., Chang, S. D. 2023: 1-7

  Abstract

  Patchy alopecia is a common adverse effect of stereotactic radiosurgery (SRS) on the calvarium and/or scalp, yet no guidelines exist for its prevention. This study aims to investigate the incidence and outcomes of patchy alopecia following SRS for patients with calvarial or scalp lesions and establish preventive guidelines.The study included 20 patients who underwent CyberKnife SRS for calvarial or scalp lesions, resulting in a total of 30 treated lesions. SRS was administered as a single fraction for 8 lesions and hypofractionated for 22 lesions. The median SRS target volume was 9.85 cc (range: 0.81-110.7 cc), and the median prescription dose was 27 Gy (range: 16-40 Gy), delivered in 1-5 fractions (median: 3). The median follow-up was 15 months.Among the 30 treated lesions, 11 led to patchy alopecia, while 19 did not. All cases of alopecia resolved within 12 months, and no patients experienced other adverse radiation effects. Lesions resulting in alopecia exhibited significantly higher biologically effective dose (BED) and single-fraction equivalent dose (SFED) on the overlying scalp compared to those without alopecia. Patients with BED and SFED exceeding 60 Gy and 20 Gy, respectively, were 9.3 times more likely to experience patchy alopecia than those with lower doses. The 1-year local tumor control rate for the treated lesions was 93.3%. Chemotherapy was administered for 26 lesions, with 11 lesions receiving radiosensitizing agents. However, no statistically significant difference was found.In summary, SRS is a safe and effective treatment for patients with calvarial/scalp masses regarding patchy alopecia near the treated area. Limiting the BED under 60 Gy and SFED under 20 Gy for the overlying scalp can help prevent patchy alopecia during SRS treatment of the calvarial/scalp mass. Clinicians can use this information to inform patients about the risk of alopecia and the contributing factors.

  View details for DOI 10.1159/000533555

  View details for PubMedID 37699370

• Definitive Treatment of Brain Metastases From a Neuroendocrine Tumor With Peptide Receptor Radionuclide Therapy With 177Lutetium DOTATATE: A Case Report. Cureus Zhang, V., Taparra, K., Fisher, G., Aparici, C., Soltys, S. G. 2023; 15 (9): e45327

  Abstract

  Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare malignancies that arise from secretory endocrine cells of the gastroenteropancreatic system. Clinical outcomes have improved for patients with GEP-NETs due to the development and recent FDA approval of 177Lutetium DOTATATE. However, the response of brain metastases from GEP-NETs from 177Lutetium DOTATATE is unreported. We present the case of an 81-year-old man with low-grade small bowel GEP-NET with liver and brain metastases treated with a total of six cycles of 177Lutetium DOTATATE. With over three years of follow-up from his initial treatment, his brain metastases have had complete or partial responses, with no need for brain radiotherapy or radiosurgery.

  View details for DOI 10.7759/cureus.45327

  View details for PubMedID 37849592

  View details for PubMedCentralID PMC10577096

• Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia Secondary to Stroke: A Systematic Review and Clinical Case Presentation. World neurosurgery Zamarud, A., Park, D. J., Ung, T. H., McCleary, T. L., Yoo, K. H., Soltys, S. G., Lim, M., Chang, S. D., Meola, A. 2023

  View details for DOI 10.1016/j.wneu.2023.08.092

  View details for PubMedID 37640262

• Glomangiopericytoma Presenting as a Middle Ear Mass. The Laryngoscope Liu, G. S., Berry, G. J., Soltys, S. G., Blevins, N. H. 2023

  Abstract

  We describe an unusual case of glomangiopericytoma presenting as a mass filling the middle ear, enveloping the ossicles, and extending into the mastoid antrum without bony destruction. Management involved three surgeries and stereotactic radiosurgery, which achieved short-term local control with no evidence of disease on MRI imaging 12 months after radiation. Facial nerve function and hearing were preserved. This is the first report to our knowledge of a glomangiopericytoma presenting as a primary temporal bone lesion. Treatment with surgery and stereotactic radiosurgery for residual or recurrent disease is a reasonable approach to achieve local control and functional preservation. Laryngoscope, 2023.

  View details for DOI 10.1002/lary.30987

  View details for PubMedID 37615366

• Stereotactic radiosurgery for sarcoma metastases to the brain: a single-institution experience. Neurosurgical focus Zamarud, A., Park, D. J., Dadey, D. Y., Yoo, K. H., Marianayagam, N. J., Yener, U., Szalkowski, G. A., Pollom, E., Soltys, S., Chang, S. D., Meola, A. 2023; 55 (2): E7

  Abstract

  Brain metastases (BMs) secondary to sarcoma are rare, and their incidence ranges from 1% to 8% of all bone and soft tissue sarcomas. Although stereotactic radiosurgery (SRS) is widely used for BMs, only a few papers have reported on SRS for sarcoma metastasizing to the brain. The purpose of this study was to evaluate the safety and effectiveness of SRS for sarcoma BM.The authors retrospectively reviewed the clinical and radiological outcomes of patients with BM secondary to histopathologically confirmed sarcoma treated with SRS, either as primary treatment or as adjuvant therapy after surgery, at their institution between January 2005 and September 2022. They also compared the outcomes of patients with hemorrhagic lesions and of those without.Twenty-three patients (9 females) with 150 BMs secondary to sarcoma were treated with CyberKnife SRS. Median age at the time of treatment was 48.22 years (range 4-76 years). The most common primary tumor sites were the heart, lungs, uterus, upper extremities, chest wall, and head and neck. The median Karnofsky Performance Status on presentation was 73.28 (range 40-100). Eight patients underwent SRS as a primary treatment and 15 as adjuvant therapy to the resection cavity. The median tumor volume was 24.1 cm3 (range 0.1-150.3 cm3), the median marginal dose was 24 Gy (range 18-30 Gy) delivered in a median of 1 fraction (range 1-5) to a median isodose line of 76%. The median follow-up was 8 months (range 2-40 months). Median progression-free survival and overall survival were 5.3 months (range 0.4-32 months) and 8.2 months (range 0.1-40), respectively. The 3-, 6-, and 12-month local tumor control (LTC) rates for all lesions were respectively 78%, 52%, and 30%. There were no radiation-induced adverse effects. LTC at the 3-, 6-, and 12-month follow-ups was better in patients without hemorrhagic lesions (100%, 70%, and 40%, respectively) than in those with hemorrhagic lesions (68%, 38%, and 23%, respectively).SRS, both as a primary treatment and as adjuvant therapy to the resection cavity after surgery, is a safe and relatively effective treatment modality for sarcoma BMs. Nonhemorrhagic lesions show better LTC than hemorrhagic lesions. Larger studies aiming to validate these results are encouraged.

  View details for DOI 10.3171/2023.5.FOCUS23168

  View details for PubMedID 37527671

• Stereotactic Radiosurgery for Contrast-Enhancing Satellite Nodules in Recurrent Glioblastoma: A Rare Case Series From a Single Institution. Cureus Park, D. J., Persad, A. R., Yoo, K. H., Marianayagam, N. J., Yener, U., Tayag, A., Ustrzynski, L., Emrich, S. C., Chuang, C., Pollom, E., Soltys, S. G., Meola, A., Chang, S. D. 2023; 15 (8): e44455

  Abstract

  Introduction Glioblastoma (GBM) is the most common malignant adult brain tumor and is invariably fatal. The standard treatment for GBM involves resection where possible, followed by chemoradiation per Stupp's protocol. We frequently use stereotactic radiosurgery (SRS) as a single-fraction treatment for small (volume ≤ 1cc) nodular recurrent GBM to the contrast-enhancing target on T1 MRI scan. In this paper, we aimed to evaluate the safety and efficacy of SRS for patients with contrast-enhancing satellite nodules in recurrent GBM. Methods This retrospective study analyzed the clinical and radiological outcomes of five patients who underwent CyberKnife (Accuray Inc., Sunnyvale, California) SRS at the institute between 2013 and 2022. Results From 96 patients receiving SRS for GBM, five (four males, one female; median age 53) had nine distinct new satellite lesions on MRI, separate from their primary tumor beds. Those nine lesions were treated with a median margin dose of 20 Gy in a single fraction. The three-, six, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was seven months, median overall survival following SRS was 10 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was separate from the T2-fluid attenuated inversion recovery (FLAIR) signal of the main tumor. Conclusion Our SRS treatment outcomes for recurrent GBM satellite lesions are consistent with existing findings. However, in a unique case, a satellite nodule distinct from the primary tumor's T2-FLAIR signal and treated with an enlarged target volume showed promising control until the patient's demise. This observation suggests potential research avenues, given the limited strategies for 'multicentric' GBM lesions.

  View details for DOI 10.7759/cureus.44455

  View details for PubMedID 37664337

  View details for PubMedCentralID PMC10470661

• Stereotactic radiosurgery for distant brain metastases secondary to esthesioneuroblastoma: a single-institution series. Neurosurgical focus Zamarud, A., Yener, U., Yoo, K. H., Park, D. J., Marianayagam, N. J., Ho, Q. A., Pollom, E., Soltys, S., Wang, L., Chang, S. D., Meola, A. 2023; 55 (2): E6

  Abstract

  Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication.A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported.Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects.In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.

  View details for DOI 10.3171/2023.5.FOCUS23216

  View details for PubMedID 37527675

• CyberKnife radiosurgery for treatment of residual or recurrent Grade 1 choroid plexus papilloma: A single institution experience. World neurosurgery Zhang, M., Park, D. J., Marianayagam, N. J., Yener, U., Soltys, S. G., Pollom, E., Chang, S. D., Meola, A. 2023

  Abstract

  Choroid plexus papillomas (CPP) are rare intraventricular brain tumors derived from the epithelium of the choroid plexus. Gross total resection has traditionally been considered curative, but residual tumor or recurrence remains possible. SRS has become particularly more important strategy for subtotally resectied and recurrent tumors. The evidence-based rationale of SRS treatment for residual or recurrent CPP in adult patients is still lacking due to its rarity.We retrospectively reviewed histopathologically confirmed cases of residual or recurrent CPP treated with SRS at our institute in the adult population between 2005 and 2022. Three patients, with five lesions, were identified with a median age of 63 years. Patients presented initially with hydrocephalus-related symptoms, although ventriculomegaly was noted only in one patient radiographically. The tumor locations were most common in 4th ventricle or along foramen of Luschka. Treatment was delivered in a single fraction in 4 lesions and in 3 fractions in 1 patient. The median follow-up was 26 months.The local tumor control rate for the lesions was 80%. One patient developed a new lesion outside the SRS field, and one lesion developed progression without need for subsequent treatment. There were no significant shrinkage of the lesions radiographically. None of the patients revealed radiation-related adverse events. No patients required surgical management after SRS treatment at our institution. Based on the literature review, our case series was the second largest retrospective series from a single institution on SRS for recurrent or residual CPP.SRS for patients with recurrent or residual CPP was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of recurrent or residual CPP.

  View details for DOI 10.1016/j.wneu.2023.07.003

  View details for PubMedID 37423336

• Stratified assessment of an FDA-cleared deep learning algorithm for automated detection and contouring of metastatic brain tumors in stereotactic radiosurgery. Radiation oncology (London, England) Wang, J. Y., Qu, V., Hui, C., Sandhu, N., Mendoza, M. G., Panjwani, N., Chang, Y. C., Liang, C. H., Lu, J. T., Wang, L., Kovalchuk, N., Gensheimer, M. F., Soltys, S. G., Pollom, E. L. 2023; 18 (1): 61

  Abstract

  Artificial intelligence-based tools can be leveraged to improve detection and segmentation of brain metastases for stereotactic radiosurgery (SRS). VBrain by Vysioneer Inc. is a deep learning algorithm with recent FDA clearance to assist in brain tumor contouring. We aimed to assess the performance of this tool by various demographic and clinical characteristics among patients with brain metastases treated with SRS.We randomly selected 100 patients with brain metastases who underwent initial SRS on the CyberKnife from 2017 to 2020 at a single institution. Cases with resection cavities were excluded from the analysis. Computed tomography (CT) and axial T1-weighted post-contrast magnetic resonance (MR) image data were extracted for each patient and uploaded to VBrain. A brain metastasis was considered "detected" when the VBrain- "predicted" contours overlapped with the corresponding physician contours ("ground-truth" contours). We evaluated performance of VBrain against ground-truth contours using the following metrics: lesion-wise Dice similarity coefficient (DSC), lesion-wise average Hausdorff distance (AVD), false positive count (FP), and lesion-wise sensitivity (%). Kruskal-Wallis tests were performed to assess the relationships between patient characteristics including sex, race, primary histology, age, and size and number of brain metastases, and performance metrics such as DSC, AVD, FP, and sensitivity.We analyzed 100 patients with 435 intact brain metastases treated with SRS. Our cohort consisted of patients with a median number of 2 brain metastases (range: 1 to 52), median age of 69 (range: 19 to 91), and 50% male and 50% female patients. The primary site breakdown was 56% lung, 10% melanoma, 9% breast, 8% gynecological, 5% renal, 4% gastrointestinal, 2% sarcoma, and 6% other, while the race breakdown was 60% White, 18% Asian, 3% Black/African American, 2% Native Hawaiian or other Pacific Islander, and 17% other/unknown/not reported. The median tumor size was 0.112 c.c. (range: 0.010-26.475 c.c.). We found mean lesion-wise DSC to be 0.723, mean lesion-wise AVD to be 7.34% of lesion size (0.704 mm), mean FP count to be 0.72 tumors per case, and lesion-wise sensitivity to be 89.30% for all lesions. Moreover, mean sensitivity was found to be 99.07%, 97.59%, and 96.23% for lesions with diameter equal to and greater than 10 mm, 7.5 mm, and 5 mm, respectively. No other significant differences in performance metrics were observed across demographic or clinical characteristic groups.In this study, a commercial deep learning algorithm showed promising results in segmenting brain metastases, with 96.23% sensitivity for metastases with diameters of 5 mm or higher. As the software is an assistive AI, future work of VBrain integration into the clinical workflow can provide further clinical and research insights.

  View details for DOI 10.1186/s13014-023-02246-z

  View details for PubMedID 37016416

  View details for PubMedCentralID 7174761

• Real-world risk of brain metastases in stage III non-small cell lung cancer in the era of PET and MRI staging. Frontiers in oncology Alhusaini, S., Lanman, T. A., Ko, R. B., Therkelsen, K. E., Eyben, R. V., Diehn, M., Soltys, S. G., Pollom, E. L., Chin, A., Vitzthum, L., Wakelee, H. A., Padda, S. K., Ramchandran, K., Loo, B. W., Neal, J. W., Nagpal, S. 2023; 13: 1139940

  Abstract

  The 2-year incidence of brain metastases (BrMs) in stage III non-small lung cell cancer (NSCLC) has been estimated to be around 30%. However, recent clinical trials have demonstrated considerably lower BrMs rates in this patient population. In this study, we aimed to review the real-world incidence, surveillance, and treatment patterns of BrMs in stage III NSCLC.Using a retrospective single-center study design, we identified patients with stage III NSCLC who received radiation with curative intent over a 10-year period. Outcome variables included BrMs incidence, overall survival (OS), and survival from date of BrMs. Additionally, we assessed patterns of BrMs surveillance in stage III NSCLC and treatment.We identified a total of 279 stage III NSCLC patients, of which 160 with adequate records were included in the final analyses [adenocarcinoma (n = 96), squamous cell carcinoma (n = 53), other histology subtype (n = 11)]. The median OS for the entire cohort was 41 months (95% CI, 28-53), while the median time from BrMs to death was 19 months (95% CI, 9-21). Twenty-three patients (14.4%) received planned surveillance brain MRIs at 6, 12, and 24 months after completion of treatment. The remaining 137 patients (85.6%) received brain MRIs at systemic recurrence (restaging) or when neurologically symptomatic. A total of 37 patients (23%) developed BrMs, with a 2-year cumulative BrMs incidence of 17% (95% CI, 11-23). A higher incidence of BrMs was identified in patients with adenocarcinoma relative to those with squamous cell carcinoma (p < 0.01). Similarly, a higher 2-year BrMs incidence was observed in patients who received planned surveillance brain MRI relative to those who did not, although statistical significance was not reached. Stereotactic radiosurgery (SRS) treated 29 of BrMs patients (78.4%) and was preferred over WBRT, which treated only 3 patients (8.1%).At our center, BrMs incidence in stage III NSCLC patients was lower than historically reported but notably higher than the incidence described in recent clinical trials. Routine BrMs surveillance potentially allows earlier detection of asymptomatic BrMs. However, asymptomatic BrMs were mostly detected on restaging MRI at the time of recurrence.

  View details for DOI 10.3389/fonc.2023.1139940

  View details for PubMedID 37035171

  View details for PubMedCentralID PMC10080021

• SUPPORT: SUrvey of Parental Leave POlicies of RadiaTion Oncology Programs and Residency Applicants. Advances in radiation oncology Baniel, C. C., Qu, V., Ponce, S. B., Taparra, K., Beadle, B., Currey, A., Lichter, K. E., Frank, J., Bagshaw, H., Soltys, S., Pollom, E. 2023; 8 (4): 101207

  Abstract

  Recruitment to radiation oncology training programs has recently declined, and gender inequities persist in radiation oncology. Policies that promote inclusivity, such as the updated American College of Graduate Medical Education parental leave policy establishing minimum parental leave requirements, may support recruitment to radiation oncology.We surveyed 2021-2022 radiation oncology residency applicants and program directors (PDs) about program-specific parental leave policies, transparency of parental leave information during the residency application and interview process, and perceptions of the effect of parenthood on residency training, career advancement, and well-being.Of 89 radiation oncology PDs, 29 (33%) completed the survey. Of 154 residency applicants (current fourth-year medical students, international applicants, or postdoctoral fellows) surveyed, 62 (40%) completed the survey. Most applicants planned to start a family during residency (53%) and reported perceived flexibility to start a family influenced their decision to pursue radiation oncology over other career specialties (55%). Many applicants viewed time in residency (nonresearch, 22%), in research (33%), and as early career faculty (24%) as the best time to start a family. A small number of applicants used program-specific parental leave policy information in determining their rank list (11%), and many applicants sought information regarding fertility health care benefits (55%). Many applicants obtained parental leave information verbally, despite expressing a preference for objective means (slide deck, 63%; website, 50%; or handout, 42%) of information sharing. PDs were all supportive of a 6-week maternity leave policy (100% agree or strongly agree with the policy) and did not feel parental leave would negatively affect a resident's ability to pursue an academic (100%) or private practice career (100%).Many radiation oncology residency applicants plan to start families during training, seek and value program-specific parental leave information and health benefits, and prefer objective means of information sharing. These findings likely reflect those who have strong views of parental leave policies.

  View details for DOI 10.1016/j.adro.2023.101207

  View details for PubMedID 37124316

  View details for PubMedCentralID PMC10130339

• Patterns of Progression in Patients with Newly Diagnosed Glioblastoma Treated with 5 mm Margins on a Phase I/II Trial of 5 Fraction Stereotactic Radiosurgery with Concurrent and Adjuvant Temozolomide. Practical radiation oncology Mendoza, M. G., Azoulay, M., Chang, S. D., Gibbs, I. C., Hancock, S. L., Pollom, E. L., Adler, J. R., Harraher, C., Li, G., Gephart, M. H., Nagpal, S., Thomas, R. P., Recht, L. D., Jacobs, L. R., Modlin, L. A., Wynne, J., Seiger, K., Fujimoto, D., Usoz, M., von Eyben, R., Choi, C. Y., Soltys, S. G. 2023

  Abstract

  BACKGROUND: In patients with newly diagnosed glioblastoma (GBM), tumor margins of at least 20 mm are the standard of care. We sought to determine the pattern of tumor progression in patients treated with 5 fraction stereotactic radiosurgery (SRS) with 5 mm margins.METHODS: Thirty adult patients with newly diagnosed GBM were treated with 5 fraction SRS in escalated doses from 25 Gy to 40 Gy with a 5 mm total treatment margin. Progression was scored as 'in-field' if the recurrent tumor was within or contiguous with the 5 mm margin, 'marginal' if between 5 and 20 mm, and 'distant' if entirely occurring greater than 20 mm. As geometric patterns of progression do not reflect the biologic dose received, we calculated the minimum equieffective dose in 2 Gy per day (EQD2) at the site of tumor recurrence. Progression was 'dosimetrically in-field' if covered by a minimum EQD2 of 48 Gy10.RESULTS: From 2010 to 2016, 27 patients had progressed. Progression was in-field in 17 (63%), marginal in 3 (11%) and distant in 7 (26%) patients. In the 3 patients with marginal progression, the minimum EQD2 to recurrent tumor were 48 Gy10, 56 Gy10 (both considered dosimetrically in-field) and 7 Gy10 (i.e., dosimetrically out-of-field). Median overall survival (OS) was 12.1 months for in-field (95%CI 8.9-17.6), 15.1 months (95%CI 10.1-not achieved) for marginal and 21.4 months (95%CI 11.2-33.5) for distant progression. Patients with radiation necrosis were less likely to have in-field progression (1 of 7; 14%) compared to those without radiation necrosis (16 of 20; 80%; p = 0.003); those with necrosis had a median overall survival of 27.2 months (95%CI 11.2-48.3) compared to 11.7 months (95%CI 8.9-17.6) for patients with no necrosis (p = 0.077).CONCLUSION: In patients with newly diagnosed GBM treated with a 5 mm CTV margin, 3 patients (11%) had marginal progression within 5-20 mm; only 1 patient (4%) may have dosimetrically benefitted from conventional 20 mm margins. Radiation necrosis was associated with in-field tumor control.

  View details for DOI 10.1016/j.prro.2023.01.008

  View details for PubMedID 36736621

• Stereotactic radiosurgery for localized cranial Langerhans cell histiocytosis: A single institution experience and review of literature. World neurosurgery Park, D. J., Marianayagam, N. J., Yener, U., Wang, L., Soltys, S. G., Pollom, E., Chang, S. D., Meola, A. 2023

  Abstract

  Langerhans cell histiocytosis (LCH) is a rare idiopathic disease characterized by the clonal proliferation of Langerhans histiocytes in various parts of the body and capable of leading to organ damage and tumor formation. Reports of cranial LCH in the adult population are extremely rare. Although surgery remains the preferred option for localized LCH lesions, the role of stereotactic radiosurgery (SRS) is emerging as well.To retrospectively review a rare case series to determine the safety and effectiveness of SRS for patients with localized cranial LCH.We retrospectively reviewed histopathologically confirmed cases of localized cranial LCH treated with SRS at our institute in the adult population between January 2005 and September 2022. Five patients were identified with a median age of 34 years (19-54 years). The tumor location was in the pituitary stalk in three patients, the orbit in one patient, and the parietal skull in one patient. The median target volume was 2.8 cc (range: 0.37-6.11). Treatment was delivered in a single fraction in 4 patients (median margin dose of 8 Gy (range: 7-10 Gy) and in 3 fractions (22.5 Gy) in 1 patient. The median follow-up was 12 years (range: 4-17). None of the patients required craniotomy for tumor debulking before or after SRS.The local tumor control rate for the lesions was 100%. All three patients with LCH in the pituitary stalk had diabetes insipidus at the initial presentation and developed panhypopituitarism after SRS. Diabetes insipidus was not improved after SRS. The other two patients presented no adverse radiation effects. Based on the literature review, our case series was the largest retrospective series on SRS for localized cranial LCH, with the longest median follow-up.SRS for patients with localized cranial LCH was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of localized cranial LCH.

  View details for DOI 10.1016/j.wneu.2023.01.053

  View details for PubMedID 36681322

• Reflections on the 2021 Accreditation Council for Graduate Medical Education and American Board of Radiology Family and Medical Leave of Absence Policies: An Opportunity to Increase Structural Support for Physicians. International journal of radiation oncology, biology, physics Baniel, C. C., Klebaner, D., Beadle, B. M., Ponce, S. E., Takiar, V., Gibbs, I. C., Soltys, S. G., Bagshaw, H. P., Chang, D. T., Le, Q. T., Pollom, E. L. 2023; 115 (1): 19-22

  View details for DOI 10.1016/j.ijrobp.2022.07.1837

  View details for PubMedID 36526381

• Novel Applications of Stereotactic Radiosurgery Beyond Oncology: Prospective Trials in Functional Radiosurgery. International journal of radiation oncology, biology, physics Trifiletti, D. M., Redmond, K. J., Kim, M. M., Soltys, S. G., Milano, M. T., Hattangadi-Gluth, J. A. 2023; 115 (1): 4-6

  View details for DOI 10.1016/j.ijrobp.2022.06.077

  View details for PubMedID 36526398

• The Art of Radiation Therapy: The Necessary Risk of Radiation Necrosis for Durable Control of Brain Metastases. International journal of radiation oncology, biology, physics Milano, M. T., Soltys, S. G., Marks, L. B., Heron, D. E., Yorke, E., Grimm, J., Jackson, A., Mihai, A., Timmerman, R. D., Xue, J., Kavanagh, B. D., Redmond, K. J. 2022

  View details for DOI 10.1016/j.ijrobp.2022.07.036

  View details for PubMedID 36400622

• Stereotactic radiosurgery for trigeminal neuralgia secondary to tumor: a single-institution retrospective series. Neurosurgical focus Hall, J. C., Ung, T. H., McCleary, T. L., Chuang, C., Gibbs, I. C., Soltys, S. G., Hayden Gephart, M., Li, G., Pollom, E. L., Chang, S. D., Meola, A. 2022; 53 (5): E3

  Abstract

  Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution's experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both.Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS.The median follow-up period was 24 (range 0.5-155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1-5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14-35) Gy, delivered in 1-5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3-60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was -1, 0 after SRS to tumor only, and -2 after SRS to both targets.SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

  View details for DOI 10.3171/2022.8.FOCUS22381

  View details for PubMedID 36321284

• Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma. Cureus Hui, C., Wu, Y. F., Liu, K., Sandhu, N., Blomain, E., Binkley, M. S., Gephart, M. H., Chang, S. D., Li, G. H., Reddy, S. A., Soltys, S. G., Pollom, E. 2022; 14 (11): e31838

  Abstract

  Purpose/Objectives Combination BRAF (vemurafenib, dabrafenib, or encorafenib) plus MEK (trametinib, cobimetinib, or binimetinib) inhibitor therapy is now widely used in the treatment of metastatic melanoma. However, data for intracranial response to these drugs are limited. We aimed to evaluate the intracranial efficacy of BRAF plus MEK inhibitors in patients with BRAF-mutant melanoma with brain metastases (BM) and to determine patterns of failure of these new agents to inform optimal integration of local intracranial therapy. Materials and methods We retrospectively reviewed charts of patients with BRAF-mutant melanoma with metastasis to the brain with at least one untreated brain metastasis at the time of initiation of BRAF plus MEK inhibitors at our institution from 2006 to 2020. We collected per-patient and per-lesion data on demographics, treatment modality, and outcomes. The cumulative incidence of local (LF), distant intracranial (DF), and extracranial failure (EF) were calculated with competing risk analysis with death as a competing risk and censored at the last brain MRI follow-up. LF was calculated on a per-lesion basis while DF and EF were calculated on a per-patient basis. DF was defined as any new intracranial lesions. Overall survival (OS) was analyzed using Kaplan-Meier. Logistic regression was used to identify predictors for LF. Results We identified 10 patients with 63 untreated brain metastases. The median age was 50.5 years. The median sum of the diameters of the five largest untreated brain metastases per patient was 20 mm (interquartile range 15-39 mm) and the median diameter for all measurable lesions was 4 mm. Median follow-up time was 9.0 months (range 1.4 months-46.2 months). Median OS was 13.6 months. The one-year cumulative incidence of LF, DF, and EF was 17.1%, 88.6, and 71.4%, respectively. The median time to LF, DF, and EF from the start of BRAF plus MEK inhibitors was 9.0 months, 4.7 months, and 7.0 months, respectively. The larger size of the BM was associated with LF on univariate analysis (odds ratio 1.13 per 1 mm increase in diameter, 95% confidence interval 1.019 to 1.308, p<0.02). Two (20%) patients eventually received stereotactic radiosurgery, and 2 (20%) received whole-brain radiotherapy for intracranial progression. Conclusion Although patients with BRAF-mutant melanoma with BM had fair local control on BRAF plus MEK inhibitors, the competing risk of death and distant intracranial and extracranial progression was high. Patients with larger brain metastases may benefit from local therapy.

  View details for DOI 10.7759/cureus.31838

  View details for PubMedID 36579260

  View details for PubMedCentralID PMC9788920

• Stratified Assessment of a Commercial Deep Learning Algorithm for Automated Detection and Contouring of Metastatic Brain Tumors in Stereotactic Radiosurgery Wang, J. Y., Qu, V., Hui, C., Sandhu, N., Mendoza, M., Panjwani, N., Lin, J. Y., Chang, Y. C., Liang, C. H., Lu, J. T., Wang, L., Kovalchuk, N., Gensheimer, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2022: E557

  View details for Web of Science ID 000892639301565

• Local Control of Brain Metastases with Osimertinib Alone in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Hui, C., Qu, V., Wang, J. Y., Von Eyben, R., Chang, Y. C., Chiang, P. L., Liang, C. H., Lin, J. Y., Lu, J. T., Li, G., Hayden, M., Myall, N., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2022: E54-E55

  View details for Web of Science ID 000892639300120

• Stereotactic Radiosurgery for Trigeminal Neuralgia Secondary to Tumor: A Single Institutional Retrospective Series Hall, J. C., Ung, T. H., McCleary, T. L., Chuang, C. F., Gibbs, I. C., Soltys, S. G., Hayden, M., Li, G., Pollom, E., Chang, S. D., Meola, A. ELSEVIER SCIENCE INC. 2022: E83

  View details for Web of Science ID 000892639300180

• Stereotactic radiosurgery for recurrent pediatric brain tumors: clinical outcomes and toxicity. Neurosurgical focus Wang, E., Gutkin, P. M., Oh, J., Pollom, E., Soltys, S. G., Grant, G. A., Prolo, L. M., Chang, S., Li, G., Fisher, P. G., Partap, S., Campen, C. J., Gibbs, I. C., Hiniker, S. M. 2022; 53 (5): E2

  Abstract

  Recurrence of brain tumors in children after the initial course of treatment remains a problem. This study evaluated the efficacy and safety of reirradiation using stereotactic radiosurgery (SRS) in patients with recurrent pediatric primary brain tumors.This IRB-approved retrospective review included pediatric patients with recurrent primary brain tumors treated at Stanford University from 2000 to 2019 using frameless SRS. Time to local failure (LF) and distant intracranial failure (DIF) were measured from the date of SRS and analyzed using competing risk analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed with the Kaplan-Meier method.In total, 37 patients aged 2-24 years (median age 11 years at recurrence) were treated for 48 intracranial tumors. Ependymoma (38%) and medulloblastoma (22%) were the most common tumor types. The median (range) single fraction equivalent dose of SRS was 16.4 (12-24) Gy. The median (range) follow-up time was 22.9 (1.5-190) months. The median OS of all patients was 36.8 months. Eight of 40 (20%) lesions with follow-up imaging locally recurred. The 2-year cumulative incidence of LF after reirradiation with SRS was 12.8% (95% CI 4.6%-25.4%). The 2-year cumulative incidence of DIF was 25.3% (95% CI 12.9%-39.8%). The median PFS was 18 months (95% CI 8.9-44). Five (10.4%) patients developed toxicities potentially attributed to SRS, including cognitive effects and necrosis.Reirradiation using SRS for recurrent pediatric brain tumors appears safe with good local control. Innovations that improve overall disease control should continue because survival outcomes after relapse remain poor.

  View details for DOI 10.3171/2022.8.FOCUS22361

  View details for PubMedID 36321285

• Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer. Journal of neuro-oncology Hui, C., Qu, V., Wang, J. Y., von Eyben, R., Chang, Y. C., Chiang, P. L., Liang, C. H., Lu, J. T., Li, G., Hayden-Gephart, M., Wakelee, H., Neal, J., Ramchandran, K., Das, M., Nagpal, S., Soltys, S., Myall, N., Pollom, E. 2022

  Abstract

  Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone.We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥ 5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB.We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9-17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p = 0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87-7.66; p < 0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49-3.04; p < 0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99-31.81; p = 0.003) were associated with LRiB.Although 1-year cumulative incidence of LRiB is < 4% with a CR or PR, 1-year cumulative incidence of LRiB is over 10% for patients with less than a PR to osimertinib on initial MRI. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery.

  View details for DOI 10.1007/s11060-022-04145-x

  View details for PubMedID 36227422

• Intracranial and Metastatic Solitary Fibrous Tumors Treated with Radiotherapy and Radiosurgery Mendoza, M., Hui, C., von Eyben, R., Pollom, E., Loo, B., Soltys, S. LIPPINCOTT WILLIAMS & WILKINS. 2022: S34

  View details for Web of Science ID 000847787800071

• Brain Metastases from Gynecologic Primary Cancers: Prognostic Factors for Local Control and Overall Survival Mendoza, M., Janchenko, L., von Eyben, R., Kidd, E., Pollom, E., Chang, S., Li, G., Kapp, D., Hayden, M., Soltys, S. LIPPINCOTT WILLIAMS & WILKINS. 2022: S34

  View details for Web of Science ID 000847787800072

• An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma. CA: a cancer journal for clinicians Hasanov, E., Yeboa, D. N., Tucker, M. D., Swanson, T. A., Beckham, T. H., Rini, B., Ene, C. I., Hasanov, M., Derks, S., Smits, M., Dudani, S., Heng, D. Y., Brastianos, P. K., Bex, A., Hanalioglu, S., Weinberg, J. S., Hirsch, L., Carlo, M. I., Aizer, A., Brown, P. D., Bilen, M. A., Chang, E. L., Jaboin, J., Brugarolas, J., Choueiri, T. K., Atkins, M. B., McGregor, B. A., Halasz, L. M., Patel, T. R., Soltys, S. G., McDermott, D. F., Elder, J. B., Baskaya, M. K., Yu, J. B., Timmerman, R., Kim, M. M., Mut, M., Markert, J., Beal, K., Tannir, N. M., Samandouras, G., Lang, F. F., Giles, R., Jonasch, E. 2022

  Abstract

  Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:000-000.

  View details for DOI 10.3322/caac.21729

  View details for PubMedID 35708940

• Executive summary of american radium society's appropriate use criteria for the postoperative management of lower grade gliomas. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Tom, M. C., Milano, M. T., Chao, S. T., Soltys, S. G., Knisely, J. P., Sahgal, A., Nagpal, S., Lo, S. S., Jabbari, S., Wang, T. J., Ahluwalia, M. S., Simonson, M., Palmer, J. D., Gephart, M. H., Halasz, L. M., Garg, A. K., Chiang, V. L., Chang, E. L. 2022

  Abstract

  Postoperative management of lower grade gliomas (grade 2 and 3) is heterogeneous. The American Radium Society's brain malignancies panel systematically reviewed and evaluated the literature to develop consensus guidelines addressing timing of postoperative therapy, monotherapy versus combined modality therapy, type of chemotherapy used with radiotherapy, and radiotherapy dose. Thirty-six studies were included. Using consensus methodology (modified Delphi), the panel voted upon representative case variants using a 9-point appropriateness scale to address key questions. Voting results were collated to develop summarized recommendations. Following gross-total surgical resection, close surveillance is appropriate for well-selected grade 2, IDH-mutant oligodendrogliomas or astrocytomas with low-risk features. For grade 2 gliomas with high-risk features or any grade 3 glioma, immediate adjuvant therapy is recommended. When postoperative therapy is administered, radiation and planned chemotherapy is strongly recommended over monotherapy. For grade 2 and 3 IDH-mutant oligodendrogliomas and astrocytomas, either adjunctive PCV (procarbazine, lomustine, vincristine) or temozolomide is appropriate. For grade 3 IDH-mutant astrocytomas, radiotherapy followed by temozolomide is strongly recommended. The recommended radiotherapy dose for grade 2 gliomas is 45-54 Gy/1.8-2.0 Gy, and for grade 3 gliomas is 59.4-60 Gy/1.8-2.0 Gy. While multiple appropriate treatment options exist, these consensus recommendations provide an evidence-based framework to approach postoperative management of lower grade gliomas.

  View details for DOI 10.1016/j.radonc.2022.03.018

  View details for PubMedID 35367527

• Radiotherapy for brain metastases from thyroid cancer: an institutional and national retrospective cohort study. Thyroid : official journal of the American Thyroid Association Blomain, E. S., Berta, S., Hug, N. F., Giao, D. M., Meola, A., Binkley, M. S., Hui, C., Churilla, T., Shahsavari, N., Desai, K., Chang, S. D., Soltys, S., Pollom, E. L. 2022

  Abstract

  BACKGROUND: Stereotactic radiosurgery (SRS) is the standard of care for patients with a limited number of brain metastases. Despite the fact that the seminal studies regarding SRS for brain metastases were largely tissue agnostic, several current national guidelines do not uniformly recommend SRS in thyroid cancer. We therefore investigated oncologic outcomes in a cohort of patients with brain metastases from thyroid cancer who received radiotherapy at our institution as well as those in a nationally representative cancer cohort, the national cancer database (NCDB).METHODS: We identified patients with thyroid cancer and brain metastases treated with radiotherapy at our institution from 2002 through 2020. For the NCDB cohort, the national database of patients with thyroid cancer was screened on the basis of brain-directed radiotherapy or brain metastases. For the institutional cohort, the cumulative risk of local failure, distant intracranial failure and radiation necrosis were calculated, adjusted for the competing risk of death. Overall survival (OS) in both cohorts was analyzed using Kaplan-Meier method. Univariate analysis was accomplished via clustered competing risks regression.RESULTS: For the institutional cohort, we identified 33 patients with 212 treated brain metastases. Overall survival was 6.6 months. The 1-year cumulative incidences of local failure and distant intracranial failures were 7.0% and 38%, respectively. The 1-year risk of radiation necrosis was 3.3%. In the NCDB cohort, there were 289 patients and median survival was 10.2 months. NCDB national practice patterns analysis showed an increasing use of SRS over time in both the entire cohort and the subset of anaplastic patients. Univariate analysis was performed for overall survival, risk of local failure, risk of regional intracranial failure and risk of radiation necrosis.CONCLUSIONS: SRS is a safe, effective and increasingly-utilized treatment for thyroid cancer brain metastases of any histology and should be the standard of care treatment.

  View details for DOI 10.1089/thy.2021.0628

  View details for PubMedID 35229625

• DSC perfusion MRI-derived fractional tumor burden and relative CBV differentiate tumor progression and radiation necrosis in brain metastases treated with stereotactic radiosurgery. American Journal of Neuroradiology ‡Kuo, F., ‡Ng, N. N., Nagpal, S., Pollom, E. L., Soltys, S., Hayden-Gephart, M., Li, G., Born, D. E., Iv, M. 2022; 43 (5): 689-695

  View details for DOI 10.3174/ajnr.A7501

• Back to the Future: Charting the Direction of Lower Grade Glioma Trials With Lessons From the Present and Past. International journal of radiation oncology, biology, physics Kim, M. M., Hattangadi-Gluth, J. A., Redmond, K. J., Trifiletti, D. M., Soltys, S. G., Milano, M. T. 1800; 112 (1): 30-34

  View details for DOI 10.1016/j.ijrobp.2021.10.002

  View details for PubMedID 34919877

• RADIOTHERAPY FOR BRAIN METASTASES FROM THYROID CANCER: A RETROSPECTIVE COHORT STUDY Blomain, E., Berta, S., Hug, N., Giao, D., Meola, A., Binkley, M., Shahsavari, N., Desai, K., Chang, S., Soltys, S., Pollom, E. OXFORD UNIV PRESS INC. 2021: 42

  View details for Web of Science ID 000757356200166

• Management of brain metastases in lung cancer: evolving roles for radiation and systemic treatment in the era of targeted and immune therapies. Neuro-oncology advances Myall, N. J., Yu, H., Soltys, S. G., Wakelee, H. A., Pollom, E. 2021; 3 (Suppl 5): v52-v62

  Abstract

  Brain metastases are a common occurrence in both non-small cell and small cell lung cancer with the potential to affect quality of life and prognosis. Due to concerns about the accessibility of the central nervous system by systemic chemotherapy agents, the management of brain metastases has historically relied on local therapies including surgery and radiation. However, novel targeted and immune therapies that improve overall outcomes in lung cancer have demonstrated effective intracranial activity. As a result, the management of brain metastases in lung cancer has evolved, with both local and systemic therapies now playing an important role. Factors such as tumor histology (non-small versus small cell), oncogenic driver mutations, and symptom burden from intracranial disease impact treatment decisions. Here, we review the current management of brain metastases in lung cancer, highlighting the roles of stereotactic radiosurgery and novel systemic therapies as well as the ongoing questions that remain under investigation.

  View details for DOI 10.1093/noajnl/vdab106

  View details for PubMedID 34859233

• Intracranial Response to Combination BRAF and MEK Inhibitor Therapy in Patients with Metastatic Melanoma Hui, C., Wu, Y., Liu, K., Sandhu, N., Blomain, E., Binkley, M., Gephart, M., Chang, S., Li, G., Reddy, S., Gibbs, I., Soltys, S., Pollom, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S48-S49

  View details for Web of Science ID 000701779700077

• American Radium Society's Appropriate Use Criteria on Postoperative Management of Lower Grade Gliomas Tom, M., Milano, M., Soltys, S., Sahgal, A., Knisely, J., Chiang, V., Nagpal, S., Lo, S., Chao, S., Jabbari, S., Wang, T., Palmer, J., Gephart, M., Garg, A., Ahluwalia, M., Halasz, L., Chang, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S51-S52

  View details for Web of Science ID 000701779700083

• American Radium Society Appropriate Use Criteria for the Management of Brain Metastases in EGFR-mutated Non-Small Cell Lung Cancer Nagpal, S., Chiang, V., Milano, M., Soltys, S., Ahluwalia, M., Chao, S., Garg, A., Gephart, M., Halasz, L., Jabbari, S., Knisely, J., Lo, S., Palmer, J., Sahgal, A., Tom, M., Wang, T., Chang, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S49-S50

  View details for Web of Science ID 000701779700080

• Radiotherapy for Management of Brain Metastases from Thyroid Cancer: A National Cancer Database Study Blomain, E., Binkley, M., Giao, D., Churilla, T., Soltys, S., Pollom, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S48

  View details for Web of Science ID 000701779700076

• Local Recurrence Outcomes of Colorectal Cancer Oligometastases Treated With Stereotactic Ablative Radiotherapy. American journal of clinical oncology Benson, K. R., Sandhu, N., Zhang, C., Ko, R., Toesca, D. A., Lee, P. E., Von Eyben, R., Diehn, M., Gensheimer, M., Maxim, P. G., Bush, K., Loo, B. W., Soltys, S. G., Pollom, E. L., Chang, D. T. 2021

  Abstract

  PURPOSE: The aim of this study was to report local failure (LF) outcomes and associated predictors in patients with oligometastatic colorectal cancer (CRC) treated with stereotactic ablative radiotherapy (SABR).MATERIALS AND METHODS: We retrospectively reviewed patients with CRC metastases to the brain, liver, spine, or lung treated with SABR between 2001 and 2016. Time to LF was summarized using cumulative incidence of LF curves with death as a competing risk.RESULTS: The analysis included a total of 130 patients and 256 lesions. Of the metastases treated, 129 (50%) were brain, 50 (20%) liver, 49 (19%) spine, and 28 (11%) lung. Median gross tumor volume was 24 mL for liver metastases, 2 mL for brain metastases, 4 mL for spine metastases, and 1 mL for lung metastases. The overall 1, 2, and 3-year cumulative incidence of LF rates were 21.6% (16.5, 27.1), 28.2% (22.3, 34.4), and 31.5% (25.2, 38.0), respectively. LF was highest among the liver metastases (1 y: 26.0%, 2 y: 38.5%), followed by spine (1 y: 25.1%, 2 y: 31.1%), brain (1 y: 20%, 2 y: 25.2%), and lung (1 y: 13.7%, 2 y: insufficient data). Metastases from right-sided primary CRC were significantly more likely to have LF (P=0.0146, HR=2.23). Biologically effective dose>70 Gy, defined using a standard linear quadratic model using alpha/beta ratio of 10 on the individual lesion level, and pre-SABR chemotherapy were also significant predictors of LF (P= 0.0009 and 0.018, respectively).CONCLUSIONS: CRC metastases treated with SABR had significantly higher rates of LF if they originated from right-sided primary CRC, compared with left-sided. Liver metastases had the highest rates of LF compared with other metastatic sites. Thus, CRC liver metastases and metastases from right-sided CRC may benefit from more aggressive radiotherapy.

  View details for DOI 10.1097/COC.0000000000000864

  View details for PubMedID 34534143

• Thecal Sac Contouring as a Surrogate for the Cauda Equina and Intra-Canal Spinal Nerve Roots for Spine Stereotactic Body Radiotherapy (SBRT): Contour Variability and Recommendations for Safe Practice. International journal of radiation oncology, biology, physics Dunne, E. M., Lo, S., Liu, M. C., Bergman, A., Kosztyla, R., Chang, E. L., Chang, U., Chao, S. T., Dea, N., Faruqi, M. S., Ghia, A. J., Redmond, K. J., Soltys, S. G., Sahgal, A. 2021

  Abstract

  PURPOSE: To present inter observer variability (IOV) in thecal sac (TS) delineation based on contours generated by eight experienced spine stereotactic body radiotherapy (SBRT) radiation oncologists, and propose contouring recommendations to standardize practice.METHODS AND MATERIALS: In the setting of a larger contouring study that reported target volume delineation guidelines specific to sacral metastases, eight academically based radiation oncologists (RO) with dedicated spine SBRT programs independently contoured the TS as a surrogate for the cauda equina and intra-canal spinal nerve roots. Uniform treatment planning simulation CT datasets fused with T1, T2 and T1 post gadolinium magnetic resonance imaging (MRI) for each case were distributed to each RO. All contours were analysed and agreement was calculated using both Dice Similarity Coefficient (DSC) and simultaneous truth and performance level estimation (STAPLE) with kappa statistics.RESULTS: A fair level of STAPLE agreement was observed between practitioners according to a mean kappa agreement of 0.38 (range, 0.21 - 0.55) and the mean DSC (± standard deviation; with range) was 0.43 (0.36 ± 0.1 - 0.53 ± 0.1). Recommendations for a reference TS contour, accounting for the variations in practice observed in this study, include: contouring the TS to encompass all the intra-thecal spinal nerve roots and, caudal to the termination of the TS, the bony canal can be contoured as a surrogate for the extra thecal nerves roots that run within it.CONCLUSION: This study shows that even amongst high volume practitioners, there is a lack of uniformity when contouring the TS. Further modifications may be required once dosimetric data on nerve tolerance to ablative doses, and pattern of failure analyses of clinical datasets utilizing these recommendations, become available. The contouring recommendations were designed as a guide to enable consistent and safe contouring across general practice.

  View details for DOI 10.1016/j.ijrobp.2021.08.023

  View details for PubMedID 34454046

• Tumor Control Following Stereotactic Radiosurgery in Patients with Vestibular Schwannomas - A Retrospective Cohort Study. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Santa Maria, P. L., Shi, Y., Aaron, K. A., Gurgel, R. K., Corrales, C. E., Soltys, S. G., Santa Maria, C., Chang, S. D., Blevins, N. H., Jackler, R. K., Gibbs, I. C. 2021

  Abstract

  BACKGROUND: To better counsel vestibular schwannoma patients, it is necessary to understand the tumor control rates of stereotactic radiosurgery (SRS).OBJECTIVES: To determine tumor control rates, factors determining control and complication rates following SRS.METHODS: Tertiary hospital retrospective cohort.RESULTS: 579 tumors (576 patients) were treated with SRS. 477 tumors (474 patients, 82%) had ≥1 year follow up and 60% (344) ≥3 years follow up. 88% of tumors had primary SRS and 6.7% salvage SRS. Median follow up time was 4.6 years. At 3 years, the tumor control rate of primary SRS was 89% (258 of 290) in sporadic tumors compared to 43% in Neurofibromatosis type II (3 of 17) (p < 0.01). Our bivariable survival data analysis showed that Neurofibromatosis type II, documented pre-SRS growth, tumor measured by maximum dimension, SRS given as nonprimary treatment increased hazard of failure to control. There was one case of malignancy and another of rapid change following intra-tumoral hemorrhage. For tumors undergoing surgical salvage (25 of 59), 56% had a total or near-total resection, 16% had postoperative CSF leak, with 12% new facial paralysis (House-Brackmann grade VI) and worsening of facial nerve outcomes (House-Brackmann grade worse in 59% at 12 mo).CONCLUSIONS: Control of vestibular schwannoma after primary SRS occurs in the large majority. Salvage surgical treatment was notable for higher rates of postoperative complications compared to primary surgery reported in the literature.

  View details for DOI 10.1097/MAO.0000000000003285

  View details for PubMedID 34353978

• Which metric quantifies dose fall-off for SRS treatments of brain lesions? Nano, T., Capaldi, D., Chuang, C., Wang, L., Soltys, S., Braunstein, S., Ma, L. ELSEVIER IRELAND LTD. 2021: S628

  View details for Web of Science ID 000709667202013

• Stereotactic Radiotherapy for Recurrent Post- Transplant Primary Central Nervous System Lymphoma CUREUS Benitez, C. M., Rahimy, E., Panjwani, N., Maeda, L. S., Soltys, S. G. 2021; 13 (7)

  View details for DOI 10.7759/cureus.16537

  View details for Web of Science ID 000679981500011

• Stereotactic Radiotherapy for Recurrent Post-Transplant Primary Central Nervous System Lymphoma. Cureus Benitez, C. M., Rahimy, E., Panjwani, N., Maeda, L. S., Soltys, S. G. 2021; 13 (7): e16537

  Abstract

  Post-transplant primary central nervous system lymphoma (PCNSL) is a rare complication of solid organ transplantation. The optimal therapy for post-transplant PCNSL is not well established and generally includes reduction of immunosuppression and chemotherapy. Progression after front-line chemotherapy is common, and whole-brain radiotherapy (WBRT) is a standard salvage treatment as there is a concern that localized treatment fields would not prevent out-of-field recurrences. However, WBRT is associated with neurotoxicity and morbidity in these patients with inherently poor prognoses. Here, we report a patient with local recurrence of post-transplant PCNSL who was treated with fractionated stereotactic radiotherapy (SRT). He had no clinical toxicity from treatment and maintained pre-treatment neurocognition and performance status. Local control was achieved for 20 months following SRT, at which point he developed an in-field recurrence. He restarted lymphoma therapy but died one month later from fungal pneumonia. For central nervous system (CNS) lymphoma, further data are needed to optimize tumor control and toxicity outcomes and identify patients in whom localized radiotherapy fields may be beneficial, avoiding the potential toxicity of WBRT.

  View details for DOI 10.7759/cureus.16537

  View details for PubMedID 34430145

  View details for PubMedCentralID PMC8378593

• In Regard to Soltys et al. International journal of radiation oncology, biology, physics Chowdhry, A. K., Milano, M. T., Soltys, S. G., Grimm, J. 2021; 110 (2): 609-611

  View details for DOI 10.1016/j.ijrobp.2021.03.007

  View details for PubMedID 33989578

• Which Metric Quantifies Dose Fall-Off for SRS Treatments of Brain Lesions? Nano, T., Capaldi, D., Chuang, C., Wang, L., Soltys, S., Boreta, L., Braunstein, S., Ma, L. WILEY. 2021

  View details for Web of Science ID 000673145402303

• Current status and recent advances in resection cavity irradiation of brain metastases. Radiation oncology (London, England) Minniti, G., Niyazi, M., Andratschke, N., Guckenberger, M., Palmer, J. D., Shih, H. A., Lo, S. S., Soltys, S., Russo, I., Brown, P. D., Belka, C. 2021; 16 (1): 73

  Abstract

  Despite complete surgical resection brain metastases are at significant risk of local recurrence without additional radiation therapy. Traditionally, the addition of postoperative whole brain radiotherapy (WBRT) has been considered the standard of care on the basis of randomized studies demonstrating its efficacy in reducing the risk of recurrence in the surgical bed as well as the incidence of new distant metastases. More recently, postoperative stereotactic radiosurgery (SRS) to the surgical bed has emerged as an effective and safe treatment option for resected brain metastases. Published randomized trials have demonstrated that postoperative SRS to the resection cavity provides superior local control compared to surgery alone, and significantly decreases the risk of neurocognitive decline compared to WBRT, without detrimental effects on survival. While studies support the use of postoperative SRS to the resection cavity as the standard of care after surgery, there areseveral issuesthat need to be investigated further with the aim of improving local control and reducing the risk of leptomeningeal disease and radiation necrosis, including the optimal dose prescription/fractionation, the timing of postoperative SRS treatment, and surgical cavity target delineation. We provide a clinical overview on current status and recent advances in resection cavity irradiation of brain metastases, focusing on relevant strategies that can improve local control and minimize the risk of radiation-induced toxicity.

  View details for DOI 10.1186/s13014-021-01802-9

  View details for PubMedID 33858474

• The Stanford stereotactic radiosurgery experience on 7000 patients over 2 decades (1999-2018): looking far beyond the scalpel. Journal of neurosurgery Fatima, N., Meola, A., Ding, V. Y., Pollom, E., Soltys, S. G., Chuang, C. F., Shahsavari, N., Hancock, S. L., Gibbs, I. C., Adler, J. R., Chang, S. D. 2021: 1–17

  Abstract

  OBJECTIVE: The CyberKnife (CK) has emerged as an effective frameless and noninvasive method for treating a myriad of neurosurgical conditions. Here, the authors conducted an extensive retrospective analysis and review of the literature to elucidate the trend for CK use in the management paradigm for common neurosurgical diseases at their institution.METHODS: A literature review (January 1990-June 2019) and clinical review (January 1999-December 2018) were performed using, respectively, online research databases and the Stanford Research Repository of patients with intracranial and spinal lesions treated with CK at Stanford. For each disease considered, the coefficient of determination (r2) was estimated as a measure of CK utilization over time. A change in treatment modality was assessed using a t-test, with statistical significance assessed at the 0.05 alpha level.RESULTS: In over 7000 patients treated with CK for various brain and spinal lesions over the past 20 years, a positive linear trend (r2 = 0.80) in the system's use was observed. CK gained prominence in the management of intracranial and spinal arteriovenous malformations (AVMs; r2 = 0.89 and 0.95, respectively); brain and spine metastases (r2 = 0.97 and 0.79, respectively); benign tumors such as meningioma (r2 = 0.85), vestibular schwannoma (r2 = 0.76), and glomus jugulare tumor (r2 = 0.89); glioblastoma (r2 = 0.54); and trigeminal neuralgia (r2 = 0.81). A statistically significant difference in the change in treatment modality to CK was observed in the management of intracranial and spinal AVMs (p < 0.05), and while the treatment of brain and spine metastases, meningioma, and glioblastoma trended toward the use of CK, the change in treatment modality for these lesions was not statistically significant.CONCLUSIONS: Evidence suggests the robust use of CK for treating a wide range of neurological conditions.

  View details for DOI 10.3171/2020.9.JNS201484

  View details for PubMedID 33799297

• A Histologic Low-Grade Glioma with 7 Gain, 10 Loss-A Wolf in Sheep's Clothing. International journal of radiation oncology, biology, physics Pollom, E. L., Soltys, S. G. 2021; 109 (5): 1137–38

  View details for DOI 10.1016/j.ijrobp.2019.11.018

  View details for PubMedID 33714521

• Reducing Radiation-Induced Cognitive Toxicity: Sparing the Hippocampus and Beyond. International journal of radiation oncology, biology, physics Redmond, K. J., Milano, M. T., Kim, M. M., Trifiletti, D. M., Soltys, S. G., Hattangadi-Gluth, J. A. 2021; 109 (5): 1131–36

  View details for DOI 10.1016/j.ijrobp.2021.01.001

  View details for PubMedID 33714520

• Leptomeningeal disease and neurologic death after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis. Advances in radiation oncology Prabhu, R. S., Turner, B. E., Asher, A. L., Marcrom, S. R., Fiveash, J. B., Foreman, P. M., Press, R. H., Buchwald, Z. S., Curran, W. J., Patel, K. R., Breen, W. G., Brown, P. D., Jethwa, K. R., Grills, I. S., Arden, J. D., Foster, L. M., Manning, M. A., Vaslow, Z. K., Burri, S. H., Soltys, S. G. 2021; 6 (2): 100644

  Abstract

  Purpose: Postoperative stereotactic radiosurgery (SRS) is associated with up to 30% risk of subsequent leptomeningeal disease (LMD). Radiographic patterns of LMD (classical sugarcoating [cLMD] vs. nodular [nLMD]) in this setting has been shown to be prognostic. However, the association of these findings with neurologic death (ND) is not well described.Methods and Materials: The records for patients with brain metastases who underwent surgical resection and adjunctive SRS to 1 lesion (SRS to other intact lesions was allowed) and subsequently developed LMD were combined from 7 tertiary care centers. Salvage radiation therapy (RT) for LMD was categorized according to use of whole-brain versus focal cranial RT.Results: The study cohort included 125 patients with known cause of death. The ND rate in these patients was 79%, and the rate in patients who underwent LMD salvage treatment (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio: 2.9; P = .04) and second LMD failure after salvage treatment (odds ratio: 3.9; P = .02) as significantly associated with ND. The ND rate was 86% for cLMD versus 68% for nLMD. Whole-brain RT was used in 95% of patients with cLMD and 52% with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (whole-brain RT: 67% vs. focal cranial RT: 68%, P = .92).Conclusions: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of ND. Classical LMD pattern (vs. nodular) and second LMD failure after salvage treatment were significantly associated with a higher risk of ND. Patients with nLMD treated with salvage focal cranial RT did not have higher ND rates compared with WBRT. Methods to decrease LMD and the subsequent high risk of ND in this setting warrant further investigation.

  View details for DOI 10.1016/j.adro.2021.100644

  View details for PubMedID 33732962

• Stereotactic Body Radiation Therapy for Spinal Metastases: Tumor Control Probability Analyses and Recommended Reporting Standards. International journal of radiation oncology, biology, physics Soltys, S. G., Grimm, J., Milano, M. T., Xue, J., Sahgal, A., Yorke, E., Yamada, Y., Ding, G. X., Li, X. A., Lovelock, D. M., Jackson, A., Ma, L., El Naqa, I., Gibbs, I. C., Marks, L. B., Benedict, S. 2021

  Abstract

  PURPOSE: We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions.METHODS AND MATERIALS: PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose.RESULTS: Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated alpha/beta = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions.CONCLUSIONS: Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data.

  View details for DOI 10.1016/j.ijrobp.2020.11.021

  View details for PubMedID 33516580

• Intracranial Grade II Meningioma Oligometastatic to the Cervical Spine. Cureus Natarajan, J. M., Born, D. E., Harsh, G., Shuer, L. M., Soltys, S. G. 2021; 13 (1): e12809

  Abstract

  For intracranial meningiomas that metastasize extracranially, an oligometastatic state exists that is intermediate between incurable, widely metastatic disease and non-metastatic curable disease. Similar to oligometastatic cancer, aggressive local treatment of meningioma oligometastases is warranted, as it may be curable. We present a patient with multiply recurrent intracranial meningiomas over 19 years, with a transformation from grade I to grade II histology, with oligometastatic disease to the C5 vertebral body. Three years following definitive spinal stereotactic radiosurgery, she remains without evidence of other metastatic diseases. Our case highlights the oncologic concept that metastatic meningioma need not be widely disseminated and provides the clinical rationale for aggressive local treatment of an oligometastatic meningioma.

  View details for DOI 10.7759/cureus.12809

  View details for PubMedID 33628677

  View details for PubMedCentralID PMC7894379

• Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases. Journal of neuro-oncology Zhang, M. n., Rodrigues, A. J., Pollom, E. L., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Neal, J. W., Padda, S. K., Ramchandran, K. J., Wakelee, H. A., Chang, S. D., Lim, M. n., Hayden Gephart, M. n., Li, G. n. 2021

  Abstract

  Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described.We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed.A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF.In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.

  View details for DOI 10.1007/s11060-020-03686-3

  View details for PubMedID 33415659

• Phase I/II Dose-Escalation Trial of 3-Fraction Stereotactic Radiosurgery for Resection Cavities From Large Brain Metastases: Health-related Quality of Life Outcomes. American journal of clinical oncology Rahimy, E., Dudley, S. A., von Eyben, R., Pollom, E. L., Seiger, K., Modlin, L., Wynne, J., Fujimoto, D., Jacobs, L. R., Chang, S. D., Gibbs, I. C., Hancock, S. L., Adler, J. R., Li, G., Choi, C. Y., Soltys, S. G. 2021; 44 (11): 588-595

  Abstract

  We investigated differences in quality of life (QoL) in patients enrolled on a phase I/II dose-escalation study of 3-fraction resection cavity stereotactic radiosurgery (SRS) for large brain metastases.Eligible patients had 1 to 4 brain metastases, one of which was a resection cavity 4.2 to 33.5 cm3. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires core-30 (QLQ-30) and brain cancer specific module (QLQ-BN20) were obtained before SRS and at each follow-up. Nine scales were analyzed (global health status; physical, social, and emotional functioning; motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty). QoL was assessed with mixed effects models. Differences ≥10 points with q-value (adjusted P-value to account for multiplicity of testing) <0.10 were considered significant.Between 2009 and 2014, 50 enrolled patients completed 277 QoL questionnaires. Median questionnaire follow-up was 11.8 months. After SRS, insomnia demonstrated significant improvement (q=0.032, -17.7 points at 15 mo post-SRS), and future uncertainty demonstrated significant worsening (q=0.018, +9.9 points at 15 mo post-SRS). Following intracranial progression and salvage SRS, there were no significant QoL changes. The impact of salvage whole brain radiotherapy could not be assessed because of limited data (n=4 patients). In the 28% of patients that had adverse radiation effect, QoL had significant worsening in 3 metrics (physical functioning, q=0.024, emotional functioning q=0.001, and future uncertainty, q=0.004).For patients treated with 3-fraction SRS for large brain metastasis cavities, 8 of 9 QoL metrics were unchanged or improved after initial SRS. Intracranial tumor progression and salvage SRS did not impact QoL. Adverse radiation effect may be associated with at least short-term QoL impairments, but requires further investigation.

  View details for DOI 10.1097/COC.0000000000000868

  View details for PubMedID 34670228

• Financial Toxicity in Patients with Brain and Spine Metastases. World neurosurgery Koenig, J. L., Sandhu, N. n., Sborov, K. n., Sabolch, A. n., Usoz, M. n., Li, G. n., Gephart, M. H., Chang, S. n., Hiniker, S. n., Soltys, S. G., Pollom, E. L. 2021

  Abstract

  Financial toxicity associated with cancer treatment has a deleterious impact on patient outcomes but has not been well-characterized among patients with metastatic cancers. We characterize the extent of financial toxicity among this population and identify factors associated with financial toxicity.We prospectively surveyed adult patients with brain and spine metastases who received radiosurgery at a large academic medical center between January 2018 and December 2019. Financial toxicity was measured with the Personal Financial Wellness (PFW) Scale.In total, 93 patients were included with a median survival of 17.7 months. Most patients had private insurance (47%) or Medicare with supplemental insurance (42%) while 11% of patients were uninsured or insured by Medicaid/Medicare/Veterans Affairs. 60% of patients were primary income earners of which 52% had dependents. The median PFW score was 7.0 (interquartile range, 5.1-9.1) with financial toxicity reported in 23 (25%) patients. After adjusting for age and education level, private insurance (OR 0.28; p=0.080) was associated with a lower likelihood of financial toxicity. At least one emergency department visit (OR 3.87; p=0.024) and a cancer-related change in employment status (OR 3.63; p=0.036) were associated with greater likelihood of reporting financial toxicity.Most poor prognosis cancer patients with brain and spine metastases treated at a tertiary center are primary income earners and experience financial toxicity. Further studies are warranted to assess the longitudinal impact of financial toxicity in patients with metastatic cancer, particularly those with at least one emergency department visit and a cancer-related change in employment status.

  View details for DOI 10.1016/j.wneu.2021.04.103

  View details for PubMedID 33940276

• Stereotactic Radiosurgery for Vestibular Schwannomas: Tumor Control Probability Analyses and Recommended Reporting Standards. International journal of radiation oncology, biology, physics Soltys, S. G., Milano, M. T., Xue, J., Tome, W. A., Yorke, E., Sheehan, J., Ding, G. X., Kirkpatrick, J. P., Ma, L., Sahgal, A., Solberg, T., Adler, J., Grimm, J., El Naqa, I. 2020

  Abstract

  PURPOSE: We sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS).METHODS AND MATERIALS: Studies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions.RESULTS: Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented.CONCLUSIONS: With current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints.

  View details for DOI 10.1016/j.ijrobp.2020.11.019

  View details for PubMedID 33375955

• Repeat Stereotactic Radiosurgery (SRS) For Brain Metastases Locally Recurrent Following Initial SRS Harandi, N. K., Modlin, L. A., Shi, S., Von Eyben, R., Pollom, E., Soltys, S. G. ELSEVIER SCIENCE INC. 2020: E733

  View details for Web of Science ID 000582521502446

• PREOPERATIVE SINGLE FRACTION RADIOSURGERY VERSUS POSTOPERATIVE FRACTIONATED RADIOSURGERY FOR RESECTED BRAIN METASTASES: A BI-INSTITUTIONAL ANALYSIS OF SAFETY AND CLINICAL OUTCOMES Prabhu, R., Shi, S., Dhakal, R., Soltys, S., Burri, S., Asher, A., Gephart, M., Ward, M., Li, G., Heinzerling, J., Pollom, E. OXFORD UNIV PRESS INC. 2020: 184

  View details for Web of Science ID 000590061300769

• Health-Related Quality of Life following Fractionated Stereotactic Radiosurgery for Large Brain Metastases Resection Cavities on a Phase I/II Trial Rahimy, E., Dudley, S. A., Von Eyben, R., Pollom, E., Soltys, S. G. ELSEVIER SCIENCE INC. 2020: S68–S69

  View details for Web of Science ID 000582521503339

• Intracranial Autograft Fat Placement to Separate the Optic Chiasm from Tumor to Improve Stereotactic Radiotherapy Dosimetry. World neurosurgery Turner, B. E., Schuler, E., Chang, S. D., Harsh, G. R., Soltys, S. G. 2020

  Abstract

  Radiation therapy for intracranial lesions is constrained by dose to neurological organs at risk. We report two cases, a newly diagnosed chondrosarcoma and a previously irradiated meningioma, with tumors which abutted the optic chiasm following sub-total resection. Definitive radiotherapy would have required either undercoverage of the tumor or treatment of the chiasm with doses posing an unacceptable risk of blindness. Therefore, the patients underwent open surgery with placement of an abdominal fat autograft to provide space between the tumor and the optic structures at risk. Patients received definitive fractionated stereotactic radiotherapy. For each patient, we retrospectively compared the treated plan (with fat autograft) to a second plan generated utilizing the pre-autograft imaging, maintaining similar tumor coverage. For the chondrosarcoma, the fat autograft reduced the optic chiasm maximum dose (Dmax) by 21% (70.4 Gy to 55.3 Gy). For the re-irradiated peri-optic meningioma, the optic chiasm Dmax was reduced by 10% (50.8 Gy to 45.9 Gy), the left optic nerve by 17% (48.9 Gy to 40.4 Gy), and the right optic nerve by 30% (32.3 Gy to 22.6 Gy). We demonstrate the utility of abdominal fat autograft placement to maximize coverage of tumor while minimizing dose to intracranial organs at risk.

  View details for DOI 10.1016/j.wneu.2020.10.110

  View details for PubMedID 33130141

• Report from the American Radium Society (ARS) Appropriate Use Criteria Brain Malignancies Panel: Treatment of Multiple Brain Metastases Milano, M., Chiang, V., Soltys, S., Wang, T., Lo, S., Brackett, A., Gephart, M., Nagpal, S., Jabbari, S., Halasz, L., Chao, S., Garg, A., Knisely, J., Sahgal, A., Chang, E. ELSEVIER SCIENCE INC. 2020: E27–E28

  View details for Web of Science ID 000579885400057

• Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain. International journal of radiation oncology, biology, physics Milano, M. T., Grimm, J., Niemierko, A., Soltys, S. G., Moiseenko, V., Redmond, K. J., Yorke, E., Sahgal, A., Xue, J., Mahadevan, A., Muacevic, A., Marks, L. B., Kleinberg, L. R. 2020

  Abstract

  PURPOSE: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).METHODS AND MATERIALS: Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases.RESULTS: Data from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V1) of 5 cm3, 10 cm3, or >15 cm3 were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For 3-fraction fSRS for brain metastases, normal brain tissue V18 <30 cm3 and V23 <7 cm3 were associated with <10% risk of radionecrosis.CONCLUSIONS: The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks.

  View details for DOI 10.1016/j.ijrobp.2020.08.013

  View details for PubMedID 32921513

• The IMPACT of Molecular Grading of Gliomas on Contemporary Clinical Practice. International journal of radiation oncology, biology, physics Milano, M. T., Chan, M. D., Minniti, G., Hattangadi-Gluth, J. A., Redmond, K. J., Soltys, S. G. 2020; 107 (5): 859–62

  View details for DOI 10.1016/j.ijrobp.2020.05.043

  View details for PubMedID 32698972

• Continuing Medical Student Education During the Coronavirus Disease 2019 (COVID-19) Pandemic: Development of a Virtual Radiation Oncology Clerkship. Advances in radiation oncology Pollom, E. L., Sandhu, N., Frank, J., Miller, J. A., Obeid, J., Kastelowitz, N., Panjwani, N., Soltys, S. G., Bagshaw, H. P., Donaldson, S. S., Horst, K., Beadle, B. M., Chang, D. T., Gibbs, I. 2020; 5 (4): 732–36

  Abstract

  Purpose: Our institution cancelled all in-person clerkships owing to the coronavirus disease 2019 pandemic. In response, we designed a virtual radiation oncology medical student clerkship.Methods and Materials: We convened an advisory panel to design a virtual clerkship curriculum. We implemented clerkship activities using a cloud-based learning management system, video web conferencing systems, and a telemedicine portal. Students completed assessments pre- and postclerkship to provide data to improve future versions of the clerkship.Results: The virtual clerkship spans 2 weeks and is graded pass or fail. Students attend interactive didactic sessions during the first week and participate in virtual clinic and give talks to the department during the second week. Didactic sessions include lectures, case-based discussions, treatment planning seminars, and material adapted from the Radiation Oncology Education Collaborative Study Group curriculum. Students also attend virtual departmental quality assurance rounds, cancer center seminars, and multidisciplinary tumor boards. The enrollment cap was met during the first virtual clerkship period (April 27 through May 8, 2020), with a total of 12 students enrolling.Conclusions: Our virtual clerkship can increase student exposure and engagement in radiation oncology. Data on clerkship outcomes are forthcoming.

  View details for DOI 10.1016/j.adro.2020.05.006

  View details for PubMedID 32775783

• Leptomeningeal disease after surgical resection and radiosurgery for brain metastases and neurologic death: A multi-institutional analysis. Prabhu, R., Turner, B. E., Asher, A. L., Marcrom, S., Fiveash, J. B., Foreman, P. M., Press, R. H., Buchwald, Z., Curran, W. J., Patel, K. R., Breen, W., Brown, P. D., Jethwa, K., Grills, I. S., Arden, J., Foster, L. M., Manning, M. A., Vaslow, Z., Burri, S., Soltys, S. G. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368301219

• Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis. Neurosurgical review Fatima, N., Pollom, E., Soltys, S., Chang, S. D., Meola, A. 2020

  Abstract

  Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56years (44-69years). With a median clinical and radiological follow-up of 44months (9-161months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p=0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r=-0.4, p=0.001), right-sided tumor (r=-0.3, p=0.03), primary SRS (r=-0.5, p≤0.001), and initial clinical presentation of hearing loss (r=-0.4, p=0.001). To achieve a LC ≥90%, a median marginal dose (Gy) of 15 (range, 12-30Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

  View details for DOI 10.1007/s10143-020-01292-5

  View details for PubMedID 32318920

• Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery clinics of North America Meola, A., Soltys, S., Schmitt, A., Gerszten, P. C., Chang, S. D. 2020; 31 (2): 231–35

  Abstract

  Benign spinal tumors are rare clinical conditions, including meningiomas, schwannomas, and neurofibromas. Although these tumors are usually treated with open surgical resection, spinal stereotactic radiosurgery may be a safe and effective alternative to surgery in selected patients.

  View details for DOI 10.1016/j.nec.2019.12.003

  View details for PubMedID 32147014

• Clinical impact of the VOLO optimizer on treatment plan quality and clinical treatment efficiency for CyberKnife. Journal of applied clinical medical physics Schuler, E., Lo, A., Chuang, C. F., Soltys, S. G., Pollom, E. L., Wang, L. 2020

  Abstract

  With the recent CyberKnife treatment planning system (TPS) upgrade from Precision 1.0 to Precision 2.0, the new VOLO optimizer was released for plan optimization. The VOLO optimizer sought to overcome some of the limitations seen with the Sequential optimizer from previous TPS versions. The purpose of this study was to investigate the clinical impact of the VOLO optimizer on treatment plan quality and clinical treatment efficiency as compared to the Sequential optimizer. Treatment plan quality was evaluated in four categories of patients: Brain Simple (BS), Brain Complex (BC), Spine Complex (SC), and Prostate (PC). A total of 60 treatment plans were compared using both the Sequential and VOLO optimizers with Iris and MLC collimation with the same clinical constraints. Metrics evaluated included estimated treatment time, monitor units (MUs) delivered, conformity index (CI), and gradient index (GI). Furthermore, the clinical impact of the VOLO optimizer was evaluated through statistical analysis of the patient population treated during the 4months before (n=297) and 4months after (n=285) VOLO introduction. Significant MU and time reductions were observed for all four categories planned. MU reduction ranged from -14% (BS Iris) to -52% (BC MLC), and time reduction ranged from -11% (BS Iris) to -22% (BC MLC). The statistical analysis of patient population before and after VOLO introduction for patients using 6D Skull tracking with fixed cone, 6D Skull tracking with Iris, and Xsight Spine tracking with Iris were -4.6%, -22.2%, and -17.8% for treatment time reduction, -1.1%, -22.0%, and -28.4% for beam reduction and -3.2%, -21.8%, and -28.1% for MU reduction, respectively. The VOLO optimizer maintains or improves the plan quality while decreases the plan complexity and improves treatment efficiency. We anticipate an increase in patient throughput with the introduction of the VOLO optimizer.

  View details for DOI 10.1002/acm2.12851

  View details for PubMedID 32212374

• A Phase I/II Trial of 5-Fraction Stereotactic Radiosurgery with 5-mm Margins with Concurrent Temozolomide in Newly Diagnosed Glioblastoma: Primary Outcomes. Neuro-oncology Azoulay, M. n., Chang, S. D., Gibbs, I. C., Hancock, S. L., Pollom, E. L., Harsh, G. R., Adler, J. R., Harrahar, C. n., Li, G. n., Hayden Gephart, M. n., Nagpal, S. n., Thomas, R. P., Recht, L. D., Jacobs, L. R., Modlin, L. A., Wynne, J. n., Seiger, K. n., Fujimoto, D. n., Usoz, M. n., von Eyben, R. n., Choi, C. Y., Soltys, S. G. 2020

  Abstract

  We sought to determine the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with 5-mm margins delivered with concurrent temozolomide in newly diagnosed glioblastoma.We enrolled adult patients with newly diagnosed glioblastoma to 5 days of SRS in a 3+3 design on 4 escalating dose levels: 25, 30, 35, and 40 Gy. Dose limiting toxicity (DLT) was defined as CTCAE Grade 3-5 acute or late CNS toxicity, including adverse radiation effect (ARE), the imaging correlate of radiation necrosis.From 2010 to 2015, 30 patients were enrolled. The median age was 66 years (range 51-86 years). The median target volume was 60 cm3 (range 14.7-137.3 cm3). DLT occurred in 2 patients: one for post-treatment cerebral edema and progressive disease at 3 weeks (Grade 4, Dose 40 Gy); another patient died 1.5 weeks following SRS from post-operative complications (Grade 5, Dose 40 Gy). Late grade 1-2 ARE occurred in 8 patients at a median of 7.6 months (range 3.2-12.6 months). No grade 3-5 ARE occurred. With a median follow-up of 13.8 months (range 1.7-64.4 months), the median survival times were: PFS 8.2 months (95%CI 4.6-10.5), OS 14.8 months (95%CI 10.9-19.9), MGMT hypermethylated 19.9 months (95%CI 10.5-33.5) vs. 11.3 months (95%CI 8.9-17.6) for no/unknown hypermethylation (p=0.03), and 27.2 months (95%CI 11.2-48.3) if late ARE occurred vs. 11.7 months (95%CI 8.9-17.6) for no ARE (p=0.08).The per-protocol MTD of 5-fraction SRS with 5-mm margins with concurrent temozolomide was 40 Gy in 5 fractions. ARE was limited to grade 1-2 and did not statistically impact survival.

  View details for DOI 10.1093/neuonc/noaa019

  View details for PubMedID 32002547

• Executive Summary from American Radium Society's Appropriate Use Criteria on Neurocognition after stereotactic radiosurgery for multiple brain metastases. Neuro-oncology Milano, M. T., Chiang, V. L., Soltys, S. G., Wang, T. J., Lo, S. S., Brackett, A. n., Nagpal, S. n., Chao, S. n., Garg, A. K., Jabbari, S. n., Halasz, L. M., Gephart, M. H., Knisely, J. P., Sahgal, A. n., Chang, E. L. 2020

  Abstract

  The ARS Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BrM) to generate consensus guidelines.The panel developed 4 key questions (KQ) to guide systematic review. From 11,614 original articles, 12 were selected. The panel developed model cases addressing KQ and potentially controversial scenarios not addressed in the systematic review (that might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness.The panel agreed that SRS-alone is usually appropriate for those with good performance status (PS) and 2-10 asymptomatic BrM, and usually not appropriate for >20 BrM. For 11-15 and 16-20 BrM there was (between 4 case variants) agreement that SRS-alone may be appropriate or disagreement on the appropriateness of SRS-alone. There was no scenario in which conventional whole brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2-4 asymptomatic BrM; WBRT for resected BrM amenable to SRS; fractionated- vs, single-fraction SRS for resected BrM, larger targets and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS-alone to all or select lesions) for patients with progressive extracranial disease, poor PS and no systemic options.For patients with 2-10 BrM, SRS-alone is an appropriate treatment option for well-selected patients with good PS. Future study is needed for those scenarios in which there was disagreement among panelists.

  View details for DOI 10.1093/neuonc/noaa192

  View details for PubMedID 32780818

• Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases. International journal of radiation oncology, biology, physics Redmond, K. J., Gui, C. n., Benedict, S. n., Milano, M. T., Grimm, J. n., Vargo, J. A., Soltys, S. G., Yorke, E. n., Jackson, A. n., El Naqa, I. n., Marks, L. B., Xue, J. n., Heron, D. E., Kleinberg, L. R. 2020

  Abstract

  As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference.Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter.TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS.

  View details for DOI 10.1016/j.ijrobp.2020.10.034

  View details for PubMedID 33390244

• Intracranial Tumor Control Following Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma. World neurosurgery Zhang, M. n., Rodrigues, A. J., Bhambhvani, H. P., Fatemi, P. n., Pollom, E. L., Gibbs, I. C., Thomas, R. P., Soltys, S. G., Hancock, S. L., Chang, S. D., Reddy, S. A., Gephart, M. H., Li, G. n. 2020

  Abstract

  Immunotherapy for melanoma patients with brain metastasis has significantly improved outcomes; however, they have also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports suggest these reactions can precede improved treatment responses. We sought to identify if such association exists for intracranial disease control.We conducted a retrospective chart review of melanoma patients who underwent immunotherapy treatment following diagnosis of brain metastasis. The study cohort was then stratified into two groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analysis were used to evaluate survival and predictors of outcomes.Fifty-two patients met inclusion criteria, seventeen of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 vs 10.5 months (p = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival, mean (33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (p = 0.013, HR = 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (p = 0.015, HR = 10.73) CONCLUSION: Immune related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to demonstrate promising outcomes as a first-line agent for melanoma with brain metastasis.

  View details for DOI 10.1016/j.wneu.2020.08.124

  View details for PubMedID 32853767

• Stereotactic Radiosurgery for Resected Brain Metastases - Does the Surgical Corridor Need to be Targeted? Practical radiation oncology Shi, S. n., Sandhu, N. n., Jin, M. n., Wang, E. n., Liu, E. n., Jaoude, J. A., Schofield, K. n., Zhang, C. n., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G. n., Gephart, M. H., Pollom, E. L., Soltys, S. G. 2020

  Abstract

  Although consensus guidelines for post-resection stereotactic radiosurgery (SRS) for brain metastases recommend the surgical corridor leading to the resection cavity be included in the SRS plan, no study has reported patterns of tumor recurrence based on inclusion or exclusion of the corridor as a target. We reviewed tumor control and toxicity outcomes of post-resection SRS for deep brain metastases based on whether or not the surgical corridor was targeted.We retrospectively reviewed patients who had resected brain metastases treated with SRS between 2007 and 2018 and included only 'deep' tumors (defined as located ≥1.0 cm from the pial surface prior to resection).In 66 deep brain metastases in 64 patients, the surgical corridor was targeted in 43 (65%). There were no statistical differences in the cumulative incidences of progression at 12-months for targeting vs. not targeting the corridor, respectively, for: overall local failure 2% (95% Confidence Interval [CI],0-11%) vs. 9% (95% CI,1-25%; p=0.25), corridor failure 0% (95% CI,0-0%) vs. 9% (95% CI,1-25%; p=0.06), cavity failure 2% (95% CI,0-11%) vs. 0% (95% CI,0-0%; p=0.91), adverse radiation effect 5% (95% CI,1-15%) vs. 13% (95% CI,3-30%; p=0.22). Leptomeningeal disease (7% (95% CI,2-18%) vs. 26% (95% CI,10-45%; p=0.03)) was higher in those without the corridor targeted.Omitting the surgical corridor in post-operative SRS for resected brain metastases was not associated with statistically significant differences in corridor or cavity recurrence or adverse radiation effect. As seen in recent prospective trials of post-resection SRS, the dominant pattern of progression is within the resection cavity; omission of the corridor would yield a smaller SRS volume that could allow for dose escalation to potentially improve local cavity control.

  View details for DOI 10.1016/j.prro.2020.04.009

  View details for PubMedID 32428766

• Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma. Neurosurgery Jin, M. C., Prolo, L. M., Wu, A. n., Azad, T. D., Shi, S. n., Rodrigues, A. J., Soltys, S. G., Pollom, E. L., Li, G. n., Hiniker, S. M., Grant, G. A. 2020

  Abstract

  Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

  View details for DOI 10.1093/neuros/nyaa023

  View details for PubMedID 32110805

• Virtual Radiation Oncology Clerkship During the COVID-19 Pandemic and Beyond. International journal of radiation oncology, biology, physics Sandhu, N., Frank, J., von Eyben, R., Miller, J., Obeid, J., Kastelowitz, N., Panjwani, N., Soltys, S., Bagshaw, H. P., Donaldson, S. S., Horst, K., Beadle, B. M., Chang, D. T., Gibbs, I. C., Pollom, E. 2020; 108 (2): 444–51

  Abstract

  PURPOSE: We evaluated the impact of a virtual radiation oncology clerkship.METHODS AND MATERIALS: We developed a 2-week virtual radiation oncology clerkship that launched on April 27, 2020. Clerkship components included a virtual clinic with radiation oncology faculty and residents, didactic lectures, student talks, and supplemental sessions such as tumor boards and chart rounds. Medical students completed pre- and post-clerkship self-assessments. Faculty and resident participants also completed surveys on their experience with virtual lectures and clinics. Pre- and post-clerkship results were compared using a 2-sided paired t test. An analysis of variance model was used to analyze the clerkship components.RESULTS: Twenty-six medical students, including 4 visiting students, enrolled over 2 clerkship periods (4 weeks). All students completed the pre- and post-clerkship self-assessments and agreed that the clerkship improved their understanding of radiation oncology. Compared with 3 (11.5%) students who agreed that they understood the daily responsibilities of a radiation oncologist before the clerkship, 22 (84.6%) students agreed and 3 (11.5%) strongly agreed that they understood the daily responsibilities of a radiation oncologist after the clerkship (P < .0001). Although 15 students (57.7%) reported an increased interest in radiation oncology because of the clerkship, the mean level of interest in radiation oncology as a career remained the same, with pre- and post-clerkship scores of 3.0 (±0.9) and 3.0 (±1.1) on a 5-point scale, respectively (P = .7). Students found virtual clinic and didactic lectures to be the most valuable components of the clerkship. Most respondents agreed (30.8%) or strongly agreed (65.4%) to recommend the clerkship to their classmates.CONCLUSIONS: Our virtual clerkship was effective in increasing medical student interest in and knowledge about radiation oncology. These data will help optimize a new paradigm of virtual radiation oncology education for medical students during COVID-19 and beyond.

  View details for DOI 10.1016/j.ijrobp.2020.06.050

  View details for PubMedID 32890529

• Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin. Journal of neurosurgery. Spine Sandhu, N. n., Benson, K. R., Kumar, K. A., Eyben, R. V., Chang, D. T., Gibbs, I. C., Hancock, S. L., Meola, A. n., Chang, S. D., Li, G. n., Hayden-Gephart, M. n., Soltys, S. G., Pollom, E. L. 2020: 1–8

  Abstract

  Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers.A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method.A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/β = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%).Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.

  View details for DOI 10.3171/2020.1.SPINE191260

  View details for PubMedID 32114530

• Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma. Frontiers in oncology Jin, M. C., Liu, E. K., Shi, S. n., Gibbs, I. C., Thomas, R. n., Recht, L. n., Soltys, S. G., Pollom, E. L., Chang, S. D., Hayden Gephart, M. n., Nagpal, S. n., Li, G. n. 2020; 10: 337

  Abstract

  Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited. Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions. Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], p = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252). Conclusion: Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.

  View details for DOI 10.3389/fonc.2020.00337

  View details for PubMedID 32219069

  View details for PubMedCentralID PMC7078164

• Stereotactic Radiosurgery After Resection of Brain Metastases: Changing Patterns of Care in the United States. World neurosurgery Chin, A. L., Li, G. n., Gephart, M. H., Sandhu, N. n., Nagpal, S. n., Soltys, S. G., Pollom, E. L. 2020

  Abstract

  Management of symptomatic brain metastases often includes surgical resection with postoperative radiotherapy. Postoperative whole brain radiotherapy (WBRT) improves intracranial control but detrimentally impacts quality of life and neurocognition. We sought to characterize the use in the United States of postoperative stereotactic radiosurgery (SRS), an evolving standard-of-care associated with reduced cognitive effects.With the MarketScan Commercial Claims and Encounters Database from 2007 to 2015, we identified patients aged 18-65 years treated with resection of a brain metastasis followed by SRS or WBRT within 60 days of surgery. Logistic regression estimated associations between co-variables (treatment year, age, sex, geographic region, place of service, insurance type, disease histology, comorbidity score, and median area household income and educational attainment) and SRS receipt.Of 4,007 patients included, 1,506 (37.6%) received SRS and 2,501 (62.4%) received WBRT. Postoperative SRS increased from 16.5% (2007-2008) to 56.8% (2014-2015). Patients residing in areas with a median household income or an educational attainment below 50th percentile were significantly less likely to receive SRS after controlling for treatment year and other demographic characteristics (p<0.01). Factors associated with higher odds of receiving SRS included younger age, female sex, melanoma histology, Western region location, hospital-based facility, and high-deductible health plan enrollment (p<0.05 for each).Postoperative SRS for brain metastases has increased from 2007 to 2015, with the majority of patients now receiving SRS over WBRT. Patients in areas of lower socioeconomic class were less likely to receive SRS, warranting further investigation of barriers to SRS adoption.

  View details for DOI 10.1016/j.wneu.2020.09.085

  View details for PubMedID 32971279

• Automated model versus treating physician for predicting survival time of patients with metastatic cancer. Journal of the American Medical Informatics Association : JAMIA Gensheimer, M. F., Aggarwal, S. n., Benson, K. R., Carter, J. N., Henry, A. S., Wood, D. J., Soltys, S. G., Hancock, S. n., Pollom, E. n., Shah, N. H., Chang, D. T. 2020

  Abstract

  Being able to predict a patient's life expectancy can help doctors and patients prioritize treatments and supportive care. For predicting life expectancy, physicians have been shown to outperform traditional models that use only a few predictor variables. It is possible that a machine learning model that uses many predictor variables and diverse data sources from the electronic medical record can improve on physicians' performance. For patients with metastatic cancer, we compared accuracy of life expectancy predictions by the treating physician, a machine learning model, and a traditional model.A machine learning model was trained using 14 600 metastatic cancer patients' data to predict each patient's distribution of survival time. Data sources included note text, laboratory values, and vital signs. From 2015-2016, 899 patients receiving radiotherapy for metastatic cancer were enrolled in a study in which their radiation oncologist estimated life expectancy. Survival predictions were also made by the machine learning model and a traditional model using only performance status. Performance was assessed with area under the curve for 1-year survival and calibration plots.The radiotherapy study included 1190 treatment courses in 899 patients. A total of 879 treatment courses in 685 patients were included in this analysis. Median overall survival was 11.7 months. Physicians, machine learning model, and traditional model had area under the curve for 1-year survival of 0.72 (95% CI 0.63-0.81), 0.77 (0.73-0.81), and 0.68 (0.65-0.71), respectively.The machine learning model's predictions were more accurate than those of the treating physician or a traditional model.

  View details for DOI 10.1093/jamia/ocaa290

  View details for PubMedID 33313792

• Impact of Proton Radiotherapy on Treatment Timing in Pediatric and Adult Patients with Central Nervous System Tumors Neuro-Oncology Practice Jin, M. C., Shi, S., Wu, A., Sandhu, N., Xiang, M., Soltys, S. G., Hiniker, S., Li, G., Pollom, E. L. 2020

  View details for DOI 10.1093/nop/npaa034

• International consensus recommendations for target volume delineation specific to sacral metastases and spinal stereotactic body radiation therapy (SBRT). Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Dunne, E. M., Sahgal, A., Lo, S. S., Bergman, A., Kosztyla, R., Dea, N., Chang, E. L., Chang, U., Chao, S. T., Faruqi, S., Ghia, A. J., Redmond, K. J., Soltys, S. G., Liu, M. C. 2019; 145: 21–29

  Abstract

  BACKGROUND AND PURPOSE: To interrogate inter-observer variability in gross tumour volume (GTV) and clinical target volume (CTV) delineation specific to the treatment of sacral metastases with spinal stereotactic body radiation therapy (SBRT) and develop CTV consensus contouring recommendations.MATERIALS AND METHODS: Nine specialists with spinal SBRT expertise representing 9 international centres independently contoured the GTV and CTV for 10 clinical cases of metastatic disease within the sacrum. Agreement between physicians was calculated with an expectation minimisation algorithm using simultaneous truth and performance level estimation (STAPLE) and with kappa statistics. Optimised confidence level consensus contours were obtained using a voxel-wise maximum likelihood approach and the STAPLE contours for GTV and CTV were based on an 80% confidence level.RESULTS: Mean GTV STAPLE agreement sensitivity and specificity was 0.70 (range, 0.54-0.87) and 1.00, respectively, and 0.55 (range, 0.44-0.64) and 1.00 for the CTV, respectively. Mean GTV and CTV kappa agreement was 0.73 (range, 0.59-0.83) and 0.59 (range, 0.41-0.70), respectively. Optimised confidence level consensus contours were identified by STAPLE analysis. Consensus recommendations for the CTV include treating the entire segment containing the disease in addition to the immediate adjacent bony anatomic segment at risk of microscopic extension.CONCLUSION: Consensus recommendations for CTV target delineation specific to sacral metastases treated with SBRT were established using expert contours. This is a critical first step to achieving standardisation of target delineation practice in the sacrum and will serve as a baseline for meaningful pattern of failure analyses going forward.

  View details for DOI 10.1016/j.radonc.2019.11.026

  View details for PubMedID 31874346

• Predicting Survival for Patients with Metastatic Disease. International journal of radiation oncology, biology, physics Benson, K. R., Aggarwal, S., Carter, J. N., von Eyben, R., Pradhan, P., Prionas, N. D., Bui, J. L., Soltys, S. G., Hancock, S., Gensheimer, M. F., Koong, A. C., Chang, D. T. 2019

  Abstract

  PURPOSE: This prospective study aimed to determine the accuracy of radiation oncologists in predicting the survival of patients with metastatic disease receiving radiotherapy and to understand factors associated with their accuracy.METHODS AND MATERIALS: This single-institution study surveyed 22 attending radiation oncologists to estimate patient survival. Survival predictions were defined as accurate if the observed survival (OS) was within the correct survival prediction category (0-6 months, >6-12 months, >12-24 months, and >24 months). The physicians made survival estimates for each course of radiation, yielding 877 analyzable predictions for 689 unique patients. Data analysis included Stuart's Tau C, logistic regression models, ordinal logistic regression models, and stepwise selection to examine variable interactions.RESULTS: Of the 877 radiation oncologists' predictions, 39.7% were accurate, 26.5% underestimations, and 33.9% overestimations. Stuart's Tau C showed low correlation between OS and survival estimates (0.3499), consistent with the inaccuracy reported in literature. However, results showed less systematic over-prediction than reported in the literature. Karnofsky performance status (KPS) was the most significant predictor of accuracy with greater accuracy for patients with shorter OS. Estimates were also more accurate for patients with lower KPS. Accuracy by patient age varied by primary site and race. Physician years of experience did not correlate with accuracy.CONCLUSIONS: The sampled radiation oncologists have relatively low accuracy in predicting patient survival. Future investigation should explore how survival estimates influence treatment decisions and how to improve survival prediction accuracy.

  View details for DOI 10.1016/j.ijrobp.2019.10.032

  View details for PubMedID 31682969

• Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors NEUROSURGERY Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2019; 85 (5): 708–16

  View details for DOI 10.1093/neuros/nyy442

  View details for Web of Science ID 000493569500063

• TTFIELDS DOSE DISTRIBUTION ALTERS TUMOR GROWTH PATTERNS: AN IMAGING-BASED ANALYSIS OF THE RANDOMIZED PHASE 3 EF-14 TRIAL Glas, M., Jeyapalan, S., Soltys, S., Hottinger, A., Toms, S. A., Levi, S., Lavy-Shahaf, G., Urman, N., Pollum, E., Ballo, M. OXFORD UNIV PRESS INC. 2019: 215

  View details for Web of Science ID 000509478705036

• Spinal cord dose tolerance to stereotactic body radiotherapy. International journal of radiation oncology, biology, physics Sahgal, A., Chang, J. H., Ma, L., Marks, L. B., Milano, M. T., Medin, P., Niemierko, A., Soltys, S. G., Tome, W. A., Wong, C. S., Yorke, E., Grimm, J., Jackson, A. 2019

  Abstract

  Spinal cord tolerance data for stereotactic body radiotherapy (SBRT) were extracted from published reports, reviewed and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (Dmax) are estimated to be associated with a 1 - 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions and 25.3 Gy in 5 fractions. For re-irradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include: cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD22) Dmax ≤ 70 Gy; SBRT thecal sac EQD22 Dmax ≤ 25 Gy, thecal sac SBRT EQD22 Dmax to cumulative EQD22 Dmax ratio ≤ 0.5, and a minimum time interval to re-irradiation of ≥ 5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates.

  View details for DOI 10.1016/j.ijrobp.2019.09.038

  View details for PubMedID 31606528

• Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients-A Retrospective Cohort Study Santa Maria, P. L., Shi, Y., Gurgel, R. K., Corrales, C., Soltys, S. G., Santa Maria, C., Murray, K., Chang, S. D., Blevins, N. H., Gibbs, I. C., Jackler, R. K. OXFORD UNIV PRESS INC. 2019: 550–59

  View details for DOI 10.1093/neuros/nyy407

  View details for Web of Science ID 000491255600014

• Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of over 500 Cavities Shi, S., Sandhu, N., Wang, E. H., Liu, E., Jaoude, J., Jin, M., Schofield, K., Zhang, C., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E90

  View details for DOI 10.1016/j.ijrobp.2019.06.2266

  View details for Web of Science ID 000485671500201

• Machine Learning Application for Accurate Dose Verification of MLC-based Robotic Stereotactic Radiosurgery and Stereotactic Body Radiotherapy Han, B., Xing, L., Soltys, S. G., Wang, L. ELSEVIER SCIENCE INC. 2019: E691

  View details for DOI 10.1016/j.ijrobp.2019.06.929

  View details for Web of Science ID 000485671502131

• A Multi-Platform Treatment Planning Benchmark Study for Spinal Radiosurgery Moustakis, C., Chan, M. H., Kim, J., Nilsson, J., Bergman, A., Bichay, T. J., Cilla, S., Deodato, F., Doro, R., Eich, H. T., Fau, P., Fong, M., Haverkamp, U., Heinze, S., Koehn, J., de Klerck, E. C., Lambrecht, U., Masi, L., Mayville, A. H., Morganti, A. G., Milder, M., Rades, D., Ramm, U., Ryu, S., Soltys, S. G., Maha, F., den Toom, W., Wang, L., Blanck, O. ELSEVIER SCIENCE INC. 2019: E768–E769

  View details for DOI 10.1016/j.ijrobp.2019.06.810

  View details for Web of Science ID 000485671502310

• A Multi-institutional Analysis of Patterns of Salvage Therapy for Leptomeningeal Disease after Surgical Resection and Radiosurgery for Brain Metastases Prabhu, R. S., Turner, B. E., Asher, A., Marcrom, S., Fiveash, J. B., Foreman, P. M., Press, R. H., Patel, K., Curran, W. J., Breen, W., Brown, P. D., Jethwa, K. R., Grills, I. S., Arden, J. D., Foster, L. M., Manning, M., Stern, J. D., Soltys, S. G., Burri, S. H. ELSEVIER SCIENCE INC. 2019: E86–E87

  View details for DOI 10.1016/j.ijrobp.2019.06.2359

  View details for Web of Science ID 000485671500194

• Spinal Cord Tolerance Guided by Stereotactic Radiosurgical Treatment of Intramedullary Arteriovenous Malformations Obeid, J. P., Muftuoglu, Y., Chang, S. D., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E124

  View details for DOI 10.1016/j.ijrobp.2019.06.2245

  View details for Web of Science ID 000485671500280

• Vertebral Compression Fracture Rates after Stereotactic Radiosurgery for Spinal Metastases Usoz, M., Dhillon, J., Kumar, K. A., Von Eyben, R., White, E. C., Ho, C. K., Azoulay, M., Fujimoto, D. K., Gibbs, I. C., Chang, S. D., Hancock, S. L., Pollom, E., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E126–E127

  View details for DOI 10.1016/j.ijrobp.2019.06.2250

  View details for Web of Science ID 000485671500285

• Factors Associated with Treatment Failure and Radiation Necrosis Following Cavity Radiosurgery for Resected Brain Metastases Wang, E. H., Shi, S., Sandhu, N., Liu, E., Jin, M., Schofield, K., Zhang, C., Jaoude, J., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E92

  View details for DOI 10.1016/j.ijrobp.2019.06.2271

  View details for Web of Science ID 000485671500206

• Stereotactic Radiosurgery for Small Cell Lung Cancer Brain Metastases Bagshaw, H. P., Taggarsi, R. S., Moding, E. J., Fawaz, Z. S., Von Eyben, R., Pollom, E., Chang, S. D., Gibbs, I. C., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E70–E71

  View details for DOI 10.1016/j.ijrobp.2019.06.2323

  View details for Web of Science ID 000485671500158

• Analysis of the EF-14 Phase 3 Trial Reveals That Tumor-Treating Fields Alter Progression Patterns in Glioblastoma Jeyapalan, S., Toms, S. A., Hottinger, A., Kleinberg, L. R., Pollom, E., Soltys, S. G., Glas, M. ELSEVIER SCIENCE INC. 2019: E100–E101

  View details for DOI 10.1016/j.ijrobp.2019.06.2292

  View details for Web of Science ID 000485671500227

• Impact of Lymphopenia on Survival Following Stereotactic Radiosurgery and Immune-Checkpoint Inhibitors Among Patients with Brain Metastases Benitez, C. M., Koenig, J. L., Sborov, K., Gibbs, I. C., Gensheimer, M. F., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: S144

  View details for DOI 10.1016/j.ijrobp.2019.06.142

  View details for Web of Science ID 000485671502710

• Financial Toxicity in Metastatic Cancer Patients Receiving Stereotactic Radiosurgery Koenig, J. L., Sborov, K., Sandhu, N., Sabolch, A., Usoz, M., Hiniker, S. M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E596–E597

  View details for DOI 10.1016/j.ijrobp.2019.06.1200

  View details for Web of Science ID 000485671501664

• Stereotactic Radiosurgery for Spine Metastases of Gastrointestinal Origin Sandhu, N., Benson, K., Kumar, K. A., Von Eyben, R., Chang, D. T., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E125–E126

  View details for DOI 10.1016/j.ijrobp.2019.06.2248

  View details for Web of Science ID 000485671500283

• Outcomes of Oligometastatic Colorectal Cancer treated with Stereotactic Ablative Radiotherapy Benson, K., Sandhu, N., Zhang, C., Ko, R. B., Toesca, D. S., Von Eyben, R., Diehn, M., Bush, K., Maxim, P. G., Gensheimer, M. F., Soltys, S. G., Loo, B. W., Pollom, E., Chang, D. T. ELSEVIER SCIENCE INC. 2019: E161–E162

  View details for DOI 10.1016/j.ijrobp.2019.06.2134

  View details for Web of Science ID 000485671500365

• Successful Use of Frameless Stereotactic Radiosurgery for Treatment of Recurrent Brain Metastases in an 18 Month Old Child. The International journal of neuroscience Rahimy, E., Chuang, C., Spunt, S. L., Mahaney, K., Donaldson, S. S., Gibbs, I. C., Soltys, S. G., Pollom, E., Hiniker, S. M. 2019: 1–6

  Abstract

  There are very few reported cases of stereotactic radiosurgery delivered in children under 3 years of age. We report an 18 month old boy with metastatic recurrence of undifferentiated round cell sarcoma to the brain which was treated with chemotherapy, resection, and robotic frameless stereotactic radiosurgery (SRS). Frameless SRS was delivered without technical difficulties, acute adverse events, or clinical sequelae 1.5 months post-radiation. Longer term follow-up will be needed to evaluate local tumor control and effects on neurocognitive development, endocrine function, and growth. This report adds to the literature of the few reported cases of successfully attempted SRS in very young children.

  View details for DOI 10.1080/00207454.2019.1655015

  View details for PubMedID 31401906

• Prognostic Factors and Treatment Patterns in the Management of Giant Cell Glioblastoma WORLD NEUROSURGERY Jin, M. C., Wu, A., Xiang, M., Azad, T. D., Soltys, S. G., Li, G., Pollom, E. L. 2019; 128: E217–E224

  View details for DOI 10.1016/j.wneu.2019.04.103

  View details for Web of Science ID 000475895100024

• A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases NEURO-ONCOLOGY Prabhu, R. S., Turner, B. E., Asher, A. L., Marcrom, S. R., Fiveash, J. B., Foreman, P. M., Press, R. H., Patel, K. R., Curran, W. J., Breen, W. G., Brown, P. D., Jethwa, K. R., Grills, I. S., Arden, J. D., Foster, L. M., Manning, M. A., Stern, J. D., Soltys, S. G., Burri, S. H. 2019; 21 (8): 1049–59

  View details for DOI 10.1093/neuonc/noz049

  View details for Web of Science ID 000493069500012

• Tumor Treating Fields alters progression patterns in glioblastoma: An imaging analysis of the EF-14 Phase III trial Jeyapalan, S., Toms, S. A., Hottinger, A., Kleinberg, L., Pollom, E., Soltys, S. G., Glas, M. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1538-7445.AM2019-CT205

  View details for Web of Science ID 000488129900182

• INO-5401 and INO-9012 delivered by electroporation (EP) in combination with cemiplimab (REGN2810) in newly-diagnosed glioblastoma (GBM) (NCT03491683) Reardon, D., Nagpal, S., Soltys, S., Brem, S., Omuro, A., De La Fuente, M., Bredlau, A., Lowy, I., Fury, M., Morrow, M., Kraynyak, K., McMullan, T., Santo, A. L., Sacchetta, B., Skolnik, J. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1538-7445.AM2019-CT114

  View details for Web of Science ID 000488129900102

• Stereotactic radiosurgery in large intracranial meningiomas: a systematic review. World neurosurgery Fatima, N., Meola, A., Pollom, E., Chaudhary, N., Soltys, S., Chang, S. 2019

  Abstract

  Gross total resection (GTR) of large intracranial meningiomas (LIMs) can be challenging and cause significant morbidity and mortality. The aim of this systematic review is to determine the clinical effectiveness and safety of Stereotactic Radiosurgery (SRS) either as primary or adjuvant therapy for LIMs, with tumor ≥2.5 cm in maximum dimension (tumor volume ≥8.1 cm3). A total of 452 tumors in 496 patients [350 females (69.3%) and 146 males (30.6%)] with median age 60 years (48 to 65 years) were included. The median tumor volume at the time of diagnosis was 16.7 cm3 (10 to 53.3cm3). The tumors were typically located in the skull-base (77.2%), while only 14.6% were in the supratentorial space. The median follow-up after SRS was 54 months (18-90 months). 87.8% of patients were treated with single session gamma knife radiosurgery (SS GKS), while the remaining 12.1% patients received non-single session (non-SS) GKS. Of 452 LIMs assessed for clinical response, 45.1% showed improvement, and 15.7% deteriorated after SRS. Radiographic tumor control at last follow-up (2-7.5 years) ranged from 84% to 100%. Overall, radiation-induced toxicity occurred in 23% of patients; with the most common adverse effect being cranial nerve neuropathy (5.5%) and peritumoral edema (PTE) (5.3%). Sub-group analysis revealed that there is 2-fold higher likelihood of improvement in clinical symptoms in patients with non-SS GKS than SS GKS [OR: 2.47; 95% (1.38-4.44); p=0.002].SRS is safe and effective in the treatment of LIMs as primary or adjuvant treatment. Further prospective studies are required to validate our results.

  View details for DOI 10.1016/j.wneu.2019.06.064

  View details for PubMedID 31226450

• Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study ONCOLOGIST Xie, L., Nagpal, S., Wakelee, H. A., Li, G., Soltys, S. G., Neal, J. W. 2019; 24 (6): 836–43

  View details for DOI 10.1634/theoncologist.2018-0264

  View details for Web of Science ID 000471906300044

• The Clinical Impact of VOLO Optimization in CyberKnife Treatment Planning Schueler, E., Lo, A., Chuang, C., Soltys, S., Wang, L. WILEY. 2019: E650

  View details for Web of Science ID 000471277705228

• Adverse Radiation Effect and Disease Control in Patients Undergoing Stereotactic Radiosurgery and Immune Checkpoint Inhibitor Therapy for Brain Metastases WORLD NEUROSURGERY Koenig, J. L., Shi, S., Sborov, K., Gensheimer, M. F., Le, G., Nagpal, S., Chang, S. D., Gibbs, I. C., Soltys, S. G., Pollom, E. L. 2019; 126: E1399–E1411

  View details for DOI 10.1016/j.wneu.2019.03.110

  View details for Web of Science ID 000469222400177

• Stereotactic radiosurgery for resected brain metastases: Does the surgical corridor need to be treated? Shi, S., Jaoude, J., Sandhu, N., Wang, E., Schofield, K., Jin, M. C., Zhang, C., Liu, E., Pollom, E. L., Soltys, S. G. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.2068

  View details for Web of Science ID 000487345804449

• Analysis of the EF-14 phase Ill trial reveals that tumor treating fields alter progression patterns in glioblastoma. Jeyapalan, S. A., Toms, S. A., Hottinger, A., Kleinberg, L., Pollom, E., Soltys, S. G., Glas, M. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.2055

  View details for Web of Science ID 000487345804437

• Prognostic Factors and Treatment Patterns in the Management of Giant Cell Glioblastoma. World neurosurgery Jin, M. C., Wu, A., Xiang, M., Azad, T. D., Soltys, S. G., Li, G., Pollom, E. L. 2019

  Abstract

  BACKGROUND: There is a lack of literature guiding treatment of giant cell glioblastoma (gcGBM), a rare subtype of glioblastoma (GBM). We used a national hospital-based registry to explore treatment patterns and outcomes associated with gcGBM.METHODS: Adult patients (age 18+) diagnosed with gcGBM or GBM between 2004-2014 were identified from the National Cancer Database (NCDB). Chi-squared analysis and Wilcoxon rank sum testing were used to compare characteristics between the gcGBM and GBM cohorts. Kaplan-Meier statistics, univariable and multivariable Cox regression, and propensity score matching were used to evaluate association between patient, tumor and treatment factors and survival outcomes. Correlation analysis was used to evaluate historical trends in the treatment of gcGBM. Landmark analysis allowed for accounting of immortal time.RESULTS: In total, 683 patients with gcGBM were identified. Patients with gcGBM had improved survival compared to patients with GBM (15.5 months from landmark vs 11.7, p < 0.001). Increased age (p < 0.001) was associated with worse survival while being of female sex (p = 0.023) and having a median income of higher than $63,000 (p = 0.004) predisposed patients to improved outcomes. Patients receiving trimodal therapy (biopsy and/or surgery, radiotherapy, and chemotherapy) experienced better outcomes compared to those receiving either biopsy and/or surgery only or biopsy and/or surgery and radiotherapy without systemic therapy (median survival 17.55 months vs 6.68 months; p < 0.001).CONCLUSION: gcGBM has favorable prognosis compared with GBM and should be aggressively managed with trimodal therapy. Prospective studies on gcGBM are warranted to better characterize gcGBM treatment outcomes.

  View details for PubMedID 31009783

• A Multi-Institutional Analysis of Presentation and Outcomes for Leptomeningeal Disease Recurrence After Surgical Resection and Radiosurgery for Brain Metastases. Neuro-oncology Prabhu, R. S., Turner, B. E., Asher, A. L., Marcrom, S. R., Fiveash, J. B., Foreman, P. M., Press, R. H., Patel, K. R., Curran, W. J., Breen, W. G., Brown, P. D., Jethwa, K. R., Grills, I. S., Arden, J. D., Foster, L. M., Manning, M. A., Stern, J. D., Soltys, S. G., Burri, S. H. 2019

  Abstract

  BACKGROUND: Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known.METHODS: Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical ("sugarcoating," cLMD).RESULTS: The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, p=0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal RT (10%), and other (16%), with 58% receiving a WBRT containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs. 68%, p=0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs. 3.3 months, p<0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs. classical) was significant, but type of salvage RT (WBRT vs. focal) was not.CONCLUSIONS: Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical "sugarcoating" LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.

  View details for PubMedID 30828727

• Long-term follow up data on difficult to treat intracranial arteriovenous malformations treated with the CyberKnife JOURNAL OF CLINICAL NEUROSCIENCE Gupta, R., Moore, J. M., Amorin, A., Appelboom, G., Chaudhary, N., Iyer, A., Soltys, S. G., Gibbs, I. C., Steinberg, G. K., Chang, S. D. 2019; 61: 120–23

  View details for DOI 10.1016/j.jocn.2018.10.109

  View details for Web of Science ID 000460844400022

• Stereotactic Radiosurgery for Pediatric and Adult Intracranial and Spinal Ependymomas. Stereotactic and functional neurosurgery Shi, S. n., Jin, M. C., Koenig, J. n., Gibbs, I. C., Soltys, S. G., Chang, S. D., Li, G. n., Hayden Gephart, M. n., Hiniker, S. M., Pollom, E. L. 2019: 1–6

  Abstract

  We report efficacy and toxicity outcomes with stereotactic radiosurgery (SRS) for intracranial and spinal ependymoma.We analyzed adult and pediatric patients with newly diagnosed or recurrent intracranial or spinal ependymoma lesions treated with SRS at our institution. Following SRS, local failure (LF) was defined as failure within or adjacent to the SRS target volume, while distant failure (DF) was defined as failure outside of the SRS target volume. Time to LF and DF was analyzed using competing risk analysis with death as a competing risk.Overall survival (OS) was calculated from the date of first SRS to the date of death or censored at the date of last follow-up using the Kaplan-Meier method.Twenty-one patients underwent SRS to 40 intracranial (n = 30) or spinal (n = 10) ependymoma lesions between 2007 and 2018, most commonly with 18 or 20 Gy in 1 fraction. Median follow-up for all patients after first SRS treatment was 54 months (range 2-157). The 1-year, 2-year, and 5-year rates of survival among patients with initial intracranial ependymoma were 86, 74, and 52%, respectively. The 2-year cumulative incidences of LF and DF after SRS among intracranial ependymoma patients were 25% (95% CI 11-43) and 42% (95% CI 22-60), respectively. No spinal ependymoma patient experienced LF, DF, or death within 2 years of SRS. Three patients had adverse radiation effects.SRS is a viable treatment option for intracranial and spinal ependymoma with excellent local control and acceptable toxicity.

  View details for DOI 10.1159/000502653

  View details for PubMedID 31590165

• Cavernous malformations are rare sequelae of stereotactic radiosurgery for brain metastases ACTA NEUROCHIRURGICA Seiger, K., Pendharkar, A. V., Samghabadi, P., Chang, S. D., Cho, N., Choi, C. H., Wang, C., Gephart, M., Soltys, S. G. 2019; 161 (1): 43-48

  View details for DOI 10.1007/s00701-018-3701-y

  View details for Web of Science ID 000455568300011

• Macrophage Exclusion after Radiation Therapy (MERT): A First in Human Phase I/II Trial using a CXCR4 Inhibitor in Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research Thomas, R. P., Nagpal, S. n., Iv, M. n., Soltys, S. G., Bertrand, S. n., Pelpola, J. S., Ball, R. L., Yang, J. n., Sundaram, V. n., Lavezo, J. L., Born, D. E., Vogel, H. n., Brown, J. M., Recht, L. n. 2019

  Abstract

  Preclinical studies have demonstrated that post-irradiation tumor revascularization is dependent on a stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-driven process in which myeloid cells are recruited from bone marrow. Blocking this axis results in survival improvement in preclinical models of solid tumors, including glioblastoma (GBM). We conducted a phase I/II study to determine the safety and efficacy of Macrophage Exclusion after Radiation Therapy (MERT) using the reversible CXCR4 inhibitor plerixafor in newly diagnosed glioblastoma patients.We enrolled 9 patients to the phase I study and an additional 20 patients to phase II using a modified toxicity probability interval (mTPI) design. Plerixafor was continuously infused intravenously via PICC line for four consecutive weeks beginning at day 35 of conventional treatment with concurrent chemo-radiation. Blood serum samples were obtained for pharmacokinetic analysis. Additional studies included relative cerebral blood volume (rCBV) analysis using MRI and histopathology analysis of recurrent tumors.Plerixafor was well tolerated with no drug-attributable grade 3 toxicities observed. At the maximum dose of 400 µg/kg/day, biomarker analysis found suprathreshold plerixafor serum levels and an increase in plasma SDF-1 levels. Median overall survival was 21.3 months (95% Confidence Interval (CI) 15.9, NA) with a progression-free survival of 14.5 months (95% CI 11.8, NA). MRI and histopathology support the mechanism of action to inhibit post-irradiation tumor revascularization.Infusion of the CXCR4 inhibitor plerixafor was well tolerated as an adjunct to standard chemo-irradiation in newly diagnosed GBM patients and improves local control of tumor recurrences.

  View details for DOI 10.1158/1078-0432.CCR-19-1421

  View details for PubMedID 31537527

• Management of Unruptured AVMs: The Pendulum Swings. International journal of radiation oncology, biology, physics Chan, M. D., Soltys, S. G., Halasz, L. M., Laack, N. N., Minniti, G. n., Kirkpatrick, J. P. 2019; 105 (4): 687–89

  View details for DOI 10.1016/j.ijrobp.2019.08.026

  View details for PubMedID 31655651

• Physiological motion of the optic chiasm and its impact on stereotactic radiosurgery dose. The British journal of radiology Xiang, M. n., Chan, C. n., Wang, L. n., Jani, K. n., Holdsworth, S. J., Iv, M. n., Pollom, E. n., Soltys, S. n. 2019: 20190170

  Abstract

  Avoidance of radiation-induced optic neuropathy (RION) from stereotactic radiosurgery (SRS) requires precise anatomical localization; however, no prior studies have characterized the physiologic motion of the optic chiasm. We measured the extent of chiasm motion and its impact on SRS dose.In this cross-sectional study, serial magnetic resonance imaging was performed in multiple planes in 11 human subjects without optic pathway abnormalities to determine chiasm motion across time. Subsequently, the measured displacement was applied to the hypothetical chiasm dose received in 11 patients treated with SRS to a perichiasmatic lesion.On sagittal images, the average anteroposterior chiasm displacement was 0.51 mm (95 % confidence interval [CI] 0.27 - 0.75 mm), and the average superior-inferior displacement was 0.48 mm (95% CI 0.22 - 0.74 mm). On coronal images, the average superior-inferior displacement was 0.42 mm (95% CI 0.13 - 0.71 mm), and the average lateral displacement was 0.75 mm (95% CI 0.42 - 1.08 mm). In 11 patients who underwent SRS to a perichiasmatic lesion, the average displacements increased the maximum chiasm dose (Dmax) by a mean of 14 % (range 6 - 23 %; p < 0.001).Average motion of the optic chiasm was approximately 0.50 - 0.75 mm, which increased chiasm Dmax by a mean of 14 %. In the occasional patient with higher-than-average chiasm motion in a region of steep dose gradient, the increase in chiasm Dmax and risk of RION could be even larger. Similarly, previously reported chiasm dose constraints may underestimate the true dose received during radiosurgery.To limit the risk of RION, clinicians may consider adding a 0.50 - 0.75 mm expansion to the chiasm avoidance structure.

  View details for PubMedID 31067077

• Perfusion MRI-Based Fractional Tumor Burden Differentiates between Tumor and Treatment Effect in Recurrent Glioblastomas and Informs Clinical Decision-Making. AJNR. American journal of neuroradiology Iv, M. n., Liu, X. n., Lavezo, J. n., Gentles, A. J., Ghanem, R. n., Lummus, S. n., Born, D. E., Soltys, S. G., Nagpal, S. n., Thomas, R. n., Recht, L. n., Fischbein, N. n. 2019

  Abstract

  Fractional tumor burden better correlates with histologic tumor volume fraction in treated glioblastoma than other perfusion metrics such as relative CBV. We defined fractional tumor burden classes with low and high blood volume to distinguish tumor from treatment effect and to determine whether fractional tumor burden can inform treatment-related decision-making.Forty-seven patients with high-grade gliomas (primarily glioblastoma) with recurrent contrast-enhancing lesions on DSC-MR imaging were retrospectively evaluated after surgical sampling. Histopathologic examination defined treatment effect versus tumor. Normalized relative CBV thresholds of 1.0 and 1.75 were used to define low, intermediate, and high fractional tumor burden classes in each histopathologically defined group. Performance was assessed with an area under the receiver operating characteristic curve. Consensus agreement among physician raters reporting hypothetic changes in treatment-related decisions based on fractional tumor burden was compared with actual real-time treatment decisions.Mean low fractional tumor burden, high fractional tumor burden, and relative CBV of the contrast-enhancing volume were significantly different between treatment effect and tumor (P = .002, P < .001, and P < .001), with tumor having significantly higher fractional tumor burden and relative CBV and lower fractional tumor burden. No significance was found with intermediate fractional tumor burden. Performance of the area under the receiver operating characteristic curve was the following: high fractional tumor burden, 0.85; low fractional tumor burden, 0.7; and relative CBV, 0.81. In comparing treatment decisions, there were disagreements in 7% of tumor and 44% of treatment effect cases; in the latter, all disagreements were in cases with scattered atypical cells.High fractional tumor burden and low fractional tumor burden define fractions of the contrast-enhancing lesion volume with high and low blood volume, respectively, and can differentiate treatment effect from tumor in recurrent glioblastomas. Fractional tumor burden maps can also help to inform clinical decision-making.

  View details for DOI 10.3174/ajnr.A6211

  View details for PubMedID 31515215

• Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis. Neurosurgical focus Fatima, N. n., Meola, A. n., Pollom, E. L., Soltys, S. G., Chang, S. D. 2019; 46 (6): E2

  Abstract

  OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

  View details for DOI 10.3171/2019.3.FOCUS1970

  View details for PubMedID 31153149

• Stereotactic radiosurgery for resected brain metastases: single-institutional experience of over 500 cavities. International journal of radiation oncology, biology, physics Shi, S. n., Sandhu, N. n., Jin, M. C., Wang, E. n., Jaoude, J. A., Schofield, K. n., Zhang, C. n., Liu, E. n., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G. n., Hayden-Gephart, M. n., Adler, J. R., Soltys, S. G., Pollom, E. L. 2019

  Abstract

  Post-operative stereotactic radiosurgery (SRS) has less detrimental impact on cognition and quality of life compared to whole brain radiotherapy (WBRT) and is increasingly used for resected brain metastases (BMs). Post-operative SRS techniques are not standardized, and there is a concern for a different pattern of failure following post-operative SRS compared to WBRT. We aim to study the efficacy, toxicity, and failure pattern of post-operative SRS.We retrospectively reviewed outcomes of patients with resected BMs treated with post-operative SRS between 2007 and 2018. Overall survival (OS) and cumulative incidences of local failure (LF), overall distant intracranial failure [distant parenchymal failure (DPF), nodular leptomeningeal disease (nLMD), classical leptomeningeal disease (cLMD)], and adverse radiation effect (ARE) were reported. Neurological death was determined for patients with leptomeningeal disease (LMD).A total of 442 patients with 501 resected BMs were treated over 475 total SRS courses. Median clinical follow-up and OS after SRS were 10.1 months [interquartile range (IQR) 3.6-20.7 months] and 13.9 months [95% confidence interval (CI) 11.8-15.2 months], respectively. At 12 months, event rates were 7% (95% CI 5%-10%) for LF, 9% (95% CI 7%-12%) for ARE, 44% (95% CI 40%-49%) for overall distant intracranial failure, 37% (95% CI 33%-42%) for DPF and 13% (95% CI 10%-17%) for LMD. The overall incidence of LMD was 15.8% (53% cLMD, 46% nLMD). cLMD was associated with shorter survival than nLMD (2.0 versus 11.2 months, p<0.01) and a higher proportion of neurological death (67% versus 41%, p=0.02). A total of 15% of patients ultimately received WBRT.We report the largest clinical experience of post-operative SRS for resected BMs, showing excellent local control and low toxicity. Intracranial failure was predominantly distant, with a rising incidence of LMD.

  View details for DOI 10.1016/j.ijrobp.2019.11.022

  View details for PubMedID 31785338

• Nodular Leptomeningeal Disease - A Distinct Pattern of Recurrence After Post-Resection Stereotactic Radiosurgery for Brain Metastases: A Multi-Institutional Study of Inter-Observer Reliability. International journal of radiation oncology, biology, physics Turner, B. E., Prabhu, R. S., Burri, S. H., Brown, P. D., Pollom, E. L., Milano, M. T., Weiss, S. E., Iv, M. n., Fischbein, N. n., Soliman, H. n., Lo, S. S., Chao, S. T., Cox, B. W., Murphy, J. D., Li, G. n., Gephart, M. H., Nagpal, S. n., Atalar, B. n., Azoulay, M. n., Thomas, R. n., Tillman, G. n., Durkee, B. Y., Shah, J. L., Soltys, S. G. 2019

  Abstract

  For brain metastases, surgical resection with postoperative stereotactic radiosurgery (SRS) is an emerging standard of care. Postoperative cavity SRS is associated with a specific, under-recognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease (cLMD). We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve inter-rater reliability (IRR) and validity in diagnosing LMD.Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system (CNS) expertise, completed a two-phase survey that included MRI imaging and treatment information for 30 patients. In the "pre-training" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "post-training" phase and relabeled the 30 cases using the 4 following labels: LR, DR, cLMD, nLMD.Inter-rater reliability (IRR) increased 34% after training (Fleiss' Kappa K=0.41 to K=0.55, p<0.001). IRR increased most among non-CNS specialists (+58%, p<0.001). Prior to training, IRR was lowest for LMD (K=0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, ≥27% of cases initially labeled LR or DR were later recognized as nLMD.This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training.

  View details for DOI 10.1016/j.ijrobp.2019.10.002

  View details for PubMedID 31605786

• Stereotactic Radiosurgery for Large Benign Intracranial Tumors. World neurosurgery Fatima, N. n., Meola, A. n., Pollom, E. n., Chang, S. D., Soltys, S. n. 2019

  Abstract

  Historically, it is stated that large intracranial tumors, herein defined as a maximum dimension of > 3cm or tumor volume >14.2 cm3, are not candidates for Stereotactic Radiosurgery (SRS). We report outcomes of patients with large benign intracranial tumors treated with SRS.With IRB approval, we retrospectively identified 74 patients with large benign intracranial tumors (59 meningiomas, 9 vestibular schwannomas, and 6 glomus jugulare tumors) treated with robotic SRS (2007-2018). Patients received definitive SRS in 47.3% of the cases, adjuvant to surgical resection in 44.6%, and salvage following past radiation treatment in 8.1%. A median tumor volume of 16.0 cm3 (10.1-65.5 cm3) received a median dose of 24.0 Gy (14.0-30.0 Gy) in a median of 3 fractions (1-5), for a median single fraction equivalent dose (SFED) (with alpha/beta of 3) of 14.8 Gy (11.3-18.0 Gy). The Kaplan-Meier estimate of tumor local control (LC) was calculated from date of SRS.With a median clinical follow-up of 32.8 months (0.6-125.9 months) and median radiological follow-up of 28.5 months (0.6-121.4 months), LC was 96.5% (95%CI:92.4-100%) at 3-years and 91.7% (95%CI:87.6-95.7%) at 5-years. Adverse radiation effect (ARE) was seen in 10 patients (13.5%) at a median of 13.5 months (7.8-34.5 months). ARE occurred in 9% of those with prior treatment compared to 5% radiation-naïve (p=0.23). With 236.4 person-years of follow-up, no secondary malignancies were seen.Despite the historical adage, we find that SRS provides high rates of LC for these large tumors, with rates of ARE similar to historical reports of SRS for smaller benign tumors.

  View details for DOI 10.1016/j.wneu.2019.10.005

  View details for PubMedID 31605862

• Long-term follow up data on difficult to treat intracranial arteriovenous malformations treated with the CyberKnife. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Gupta, R., Moore, J. M., Amorin, A., Appelboom, G., Chaudhary, N., Iyer, A., Steinberg, G. K., Chang, S. D., Soltys, S., Gibbs, I. 2018

  Abstract

  INTRODUCTION: The CyberKnife, a frameless, robotic, stereotactic device, has been developed to radiosurgically treat arteriovenous malformations (AVMs). While most AVMs are obliterated within two-to-three years, a subset remain recalcitrant; long-term data on these difficult to treat AVMs are limited in the neurosurgical literature.MATERIALS AND METHODS: A retrospective analysis of all patients who underwent CyberKnife treatment for intracranial AVMs at a single U.S. institution between 2002 and 2012, whose AVMs had failed to obliterate within 48 months or longer from the treatment start date, were eligible for inclusion.RESULTS: Eleven patients (9 AVMs; 7 males, 2 females) were followed for an average of 85.2 months (range 56.2-119.4). The median lesion size was 3.5 cm (range: 2.8-8.0 cm) and median Spetzler-Martin grade was 3 (range: 2-5). All AVMs were treated with one radiation dose (median prescribed dose was 18.0 Gy; median Dmax: 23.7 Gy). Six (66.7%) were obliterated in a median time of 84 months (range: 52-94 months), while 3 (33.3%) remained active after a median of 90.8 months (range 69.7-119.4). Transient, post-radiosurgery adverse radiation effects occurred in 5 (55.6%) cases. One (11.1%) patient had an acute hemorrhage from the AVM after radiosurgery. Four (44.4%) patients underwent repeat radiosurgery and/or embolization. Three of these lesions eventually obliterated, while 1 did not.CONCLUSION: The median time to obliteration was 84 months. Two-thirds of AVMs which persisted for over 4 years following initial radiosurgery treatment eventually obliterated. Transient post-radiosurgery adverse effects were common; delayed hemorrhages were rare in our case series.

  View details for PubMedID 30587419

• Clinical factors associated with mortality within three months after radiosurgery of asymptomatic brain metastases from non-small cell lung cancer JOURNAL OF NEURO-ONCOLOGY Kakusa, B., Han, S., Aggarwal, S., Liu, B., Li, G., Soltys, S., Gephart, M. 2018; 140 (3): 705-715

  View details for DOI 10.1007/s11060-018-03002-0

  View details for Web of Science ID 000451635500024

• Advance Care Planning Needs in Patients With Glioblastoma Undergoing Radiotherapy JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Pollom, E. L., Sborov, K. D., Soltys, S. G., Asch, S. M., Sudore, R. L., Aslakson, R. A. 2018; 56 (6): E6–E8

  View details for DOI 10.1016/j.jpainsymman.2018.08.021

  View details for Web of Science ID 000451633700003

• Radiographic Rate and Clinical Impact of Pseudarthrosis in Spine Radiosurgery for Metastatic Spinal Disease. Cureus Zhang, M., Appelboom, G., Ratliff, J. K., Soltys, S. G., Adler, J. R., Park, J., Chang, S. D. 2018; 10 (11): e3631

  Abstract

  Purpose Pseudarthrosis within the spine tumor population is increased from perioperative radiation and complex stabilization for invasive and recurrent pathology. We report the radiographic and clinical rates of pseudarthrosis following multiple courses of instrumented fusion and perioperative stereotactic radiosurgery (SRS). Methods We performed a single institution review of 418 patients treated with non-isocentric SRS for spine between October 2002 and January 2013, identifying those with spinal instrumentation and greater than six months of follow-up. Surgical history, radiation planning, and radiographic outcomes were documented. Results Eleven patients whomet criteria for inclusion underwent 21 sessions of spinal SRS and 16 instrumented operations. Radiographic follow-up was 48.9 months; 3/11 (27%) were with radiographic hardware failure, and one (9%) separate case ultimately warranted externalization due to tumor recurrence. SRS was administered to treat progression of disease in 12/21 (57%) procedures, and residual lesions in 7/11 (64%) procedures. Following first and second SRS, 8/11 (73%) and 2/7 (29%) patients were with symptomatic improvement, respectively. Conclusion Risk of pseudarthrosis following SRS for patients with oncologic spinal lesions will become increasingly apparent with the optimized management of and survival from spinal pathologies. We highlight how the need for local control outpaces the risk of instrumentation failure.

  View details for PubMedID 30705790

• Adverse Radiation Effect and Disease Control in Patients Undergoing Concurrent Stereotactic Radiosurgery and Immunotherapy for Brain Metastases Koenig, J. L., Sborov, K., Sandhu, N., Gensheimer, M. F., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2018: E275–E276

  View details for DOI 10.1016/j.ijrobp.2018.07.888

  View details for Web of Science ID 000447811600633

• Radiographic Rate and Clinical Impact of Pseudarthrosis in Spine Radiosurgery for Metastatic Spinal Disease CUREUS Zhang, M., Appelboom, G., Ratliff, J. K., Soltys, S. G., Adler, J. R., Park, J., Chang, S. D. 2018; 10 (11)

  View details for DOI 10.7759/cureus.3631

  View details for Web of Science ID 000458695500098

• One-Week Chemoradiotherapy is Associated with Less Treatment-Related Lymphopenia Compared to a Standard Treatment Course for Newly Diagnosed Glioblastoma Fujimoto, D. K., Sborov, K., Von Eyben, R., Osmundson, E. C., Thomas, R., Nagpal, S., Soltys, S. G. ELSEVIER SCIENCE INC. 2018: S172

  View details for DOI 10.1016/j.ijrobp.2018.07.039

  View details for Web of Science ID 000447811602604

• Patterns of Failure and Outcomes Based On Management of Leptomeningeal Disease after Surgical Resection and Radiosurgery for Brain Metastases: A Multi-Institutional Analysis Prabhu, R. S., Soltys, S. G., Turner, B. E., Marcrom, S., Fiveash, J. B., Foreman, P. M., Press, R. H., Patel, K., Curran, W. J., Breen, W., Brown, P. D., Jethwa, K. R., Grills, I. S., Arden, J. D., Foster, L. M., Manning, M., Stern, J. D., Asher, A., Burri, S. H. ELSEVIER SCIENCE INC. 2018: S142–S143

  View details for DOI 10.1016/j.ijrobp.2018.06.348

  View details for Web of Science ID 000447811602543

• Consensus Guidelines for Target Volume Definition of the Sacrum in Spinal Stereotactic Body Radiation Therapy (SBRT) Dunne, E. M., Sahgal, A., Lo, S. S., Bergman, A., Kosztyla, R., Chang, E. L., Chang, U., Chao, S. T., Ghia, A. J., Redmond, K. J., Soltys, S. G., Faruqi, S., Liu, M. C. ELSEVIER SCIENCE INC. 2018: E214

  View details for DOI 10.1016/j.ijrobp.2018.07.746

  View details for Web of Science ID 000447811600494

• Radiation-Induced Edema after Single or Multi-Fraction Stereotactic Radiosurgery (SRS) for Non-Base of Skull (non-BOS) Meningioma: A Pooled Analysis Milano, M. T., Sharma, M., Soltys, S. G., Sahgal, A., Usuki, K. Y., Saenz, J. M., Grimm, J., El Naqa, I. ELSEVIER SCIENCE INC. 2018: E305

  View details for DOI 10.1016/j.ijrobp.2018.07.958

  View details for Web of Science ID 000447811600701

• Nodular Leptomeningeal Disease - A Distinct Pattern of Recurrence after Post-Resection Stereotactic Radiosurgery for Brain Metastases: A Multi-Institutional Study of Inter-Observer Reliability Turner, B. E., Prabhu, R. S., Burri, S. H., Brown, P. D., Pollom, E., Milano, M. T., Weiss, S. E., Iv, M., Fischbein, N., Soliman, H., Lo, S. S., Soltys, S. G. ELSEVIER SCIENCE INC. 2018: E363–E364

  View details for DOI 10.1016/j.ijrobp.2018.07.1091

  View details for Web of Science ID 000447811601118

• Cavernous malformations are rare sequelae of stereotactic radiosurgery for brain metastases. Acta neurochirurgica Seiger, K., Pendharkar, A. V., Samghabadi, P., Chang, S. D., Cho, N., Choi, C. Y., Wang, C., Gephart, M. H., Soltys, S. G. 2018

  Abstract

  The development of cavernous malformations many years following conventionally fractionated brain irradiation is well recognized and commonly reported. However, cavernous malformation induction following stereotactic radiosurgery (SRS) is largely unreported. Herein, we describe two cases of cavernous malformation formation years following SRS for brain metastases. A 20-year-old woman with breast cancer brain metastases received treatment with whole brain radiotherapy (WBRT), then salvage SRS 1.4years later for progression of a previously treated metastasis. This lesion treated with SRS had hemorrhagic enlargement 3.0years after SRS. Resection revealed a cavernous malformation. A 25-year-old woman had SRS for a brain metastasis from papillary thyroid carcinoma. Resection of a progressive, hemorrhagic lesion within the SRS field 2years later revealed both recurrent carcinoma as well as cavernous malformation. As patients with brain metastases live longer following SRS, our cases highlight that the differential diagnosis of an enlarging enhancing lesion within a previous SRS field includes not only cerebral necrosis and tumor progression but also cavernous malformation induction.

  View details for PubMedID 30328524

• Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients-A Retrospective Cohort Study. Neurosurgery Santa Maria, P. L., Shi, Y., Gurgel, R. K., Corrales, C. E., Soltys, S. G., Santa Maria, C., Murray, K., Chang, S. D., Blevins, N. H., Gibbs, I. C., Jackler, R. K. 2018

  Abstract

  BACKGROUND: An understanding of the hearing outcomes is needed for treatment counseling for patients with vestibular schwannomas (VS).OBJECTIVE: To determine long-term hearing results following stereotactic radiosurgery (SRS) for VS and identify any influential variables.METHODS: Tertiary hospital retrospective cohort.RESULTS: There were 579 tumors (576 patients) treated with SRS. Eighty-two percent (473) of tumors had ≥1 yr and 59% (344 ≥3 yr follow-up. In the 244 tumor ears, with measurable hearing before SRS who were followed ≥1 yr, 14% (31) had improved hearing, 13% (29) unchanged hearing, and 74% (158) had worsened hearing. In 175 patients with ≥3 yr follow-up and who had measurable hearing pretreatment, 6% (11 ears) improved hearing, 31% (54 ears) unchanged hearing, and 63% (110 ears) had worsened hearing. Patients with tumors with larger target volumes (P=0.040) and with neurofibromatosis type 2 (NF2; P=0.017) were associated with poorer hearing (P=0.040). Patients with word recognition scores (WRS) of 50% or poorer had tumors with a larger volume (P=0.0002), larger linear size (P=0.032), and NF2 (P=0.045). Traditionally reported hearing outcomes using the Gardner Robertson maintenance of PTA ≤50 db or WRS ≥50% were 48% at 3 yr, which overestimates hearing outcomes compared to the above reporting standards.CONCLUSION: Hearing declines over time in VS treated with SRS in a high proportion of cases. The frequency and magnitude of long-term hearing decline following SRS argues against prophylactic radiation for small tumors in hearing ears with undetermined growth behavior.

  View details for PubMedID 30247723

• Advance care planning needs in patients with glioblastoma undergoing radiotherapy. Journal of pain and symptom management Pollom, E., Sborov, K., Soltys, S. G., Asch, S. M., Sudore, R., Aslakson, R. A. 2018

  View details for PubMedID 30201484

• Population description and clinical response assessment for spinal metastases: part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report NEURO-ONCOLOGY Laufer, I., Lo, S. S., Chang, E. L., Sheehan, J., Guckenberger, M., Sohn, M., Ryu, S., Foote, M., Muacevic, A., Soltys, S. G., Chao, S., Myrehaug, S., Gerszten, P. C., Lis, E., Maralani, P., Bilsky, M., Fisher, C., Rhines, L., Verlaan, J., Schiff, D., Fehlings, M. G., Ma, L., Chang, S., Parulekar, W. R., Vogelbaum, M. A., Sahgal, A. 2018; 20 (9): 1215–24

  Abstract

  Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group.SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches.Published literature, expert survey and ongoing clinical trials were used in to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurologic and functional status and symptom severity.Accurate description of patient population and therapy effects requires a combination of clinician-based and patient reported outcome (PRO) measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and post-operative spine SBRT.

  View details for PubMedID 29590465

  View details for PubMedCentralID PMC6071663

• Treatment planning for spinal radiosurgery STRAHLENTHERAPIE UND ONKOLOGIE Moustakis, C., Chan, M. H., Kim, J., Nilsson, J., Bergman, A., Bichay, T. J., Palazon Cano, I., Cilla, S., Deodato, F., Doro, R., Dunst, J., Eich, H., Fau, P., Fong, M., Haverkamp, U., Heinze, S., Hildebrandt, G., Imhoff, D., de Klerck, E., Koehn, J., Lambrecht, U., Loutfi-Krauss, B., Ebrahimi, F., Masi, L., Mayville, A. H., Mestrovic, A., Milder, M., Morganti, A. G., Rades, D., Ramm, U., Rodel, C., Siebert, F., den Toom, W., Wang, L., Wurster, S., Schweikard, A., Soltys, S. G., Ryu, S., Blanck, O. 2018; 194 (9): 843–54

  Abstract

  To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches.Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system.All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002).High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

  View details for PubMedID 29802435

• Survival impact of postoperative radiotherapy timing in pediatric and adolescent medulloblastoma NEURO-ONCOLOGY Chin, A. L., Moding, E. J., Donaldson, S. S., Gibbs, I. C., Soltys, S. G., Hiniker, S. M., Pollom, E. L. 2018; 20 (8): 1133–41

  View details for DOI 10.1093/neuonc/noy001

  View details for Web of Science ID 000438338000014

• Correlation between small-volume spinal cord doses for spine stereotactic body radiotherapy (SBRT). Journal of radiosurgery and SBRT Ma, L., Wang, L., Lee, Y., Tseng, C. L., Soltys, S., Braunstein, S., Sahgal, A. 2018; 5 (3): 229-236

  Abstract

  Doses to small spinal cord isodose volume (such as those ranging from Dmax 0.0 cc to 0.5 cc) as well as to large volumes (such as those ranging from 0.5 cc to 3.0 cc) are critical parameters to guide safe practice of spine SBRT. We here report a mathematical formula that links the most probable dose volume limits together for common spine SBRT cases.Methods and materials: A dose ripple formula parameterized with equivalent dose radius (EDR) was derived to model spinal cord small-volume doses for a spine SBRT treatment. A cohort of spine SBRT cases (n=68), treated with either a robotic x-band linac or a conventional S-band linac, was selected to verify the model predictions. The mean prescription dose was 22± 4 Gy (range, 12-40 Gy) delivered in 2±1 fractions. The mean and median target volume was 39.4±42.5 cc and 30.3 cc (range, 0.24-264.2 cc), respectively. Direct correlations between the spinal cord Dmax and variable spinal cord doses of increasing isodose volumes (ranging from 0.0 cc to 3.0 cc) of different planning organ-at-risk volumes (PRVs) were investigated. The PRV structures for the study included the true cord, thecal sac and the true cord plus variable margins ranging from 1.0 mm to 3.0 mm.No direct linear correlation was observed amongst the small volume doses to the spinal cord PRVs. However, strong linear correlations (R2 > 0.96) for all the studied PRVs were observed when correlating EDRs amongst isodose volumes ranging from 0.0 cc to 3.0 cc. In particular, EDR dependence was found to differ significantly for the thecal sac versus the spinal cord with or without 1-3 millimeter margins. With strong EDR correlation, the most probable relationship among the small-volume dose limits was derived for the spinal cord PRVs.An analytical formula linked the most probable pin-point/small isodose volume doses with relatively large isodose volume doses of the spinal cord for spine SBRT. As a result, a small number of dose limits such as Dmax or D(0.35cc) are likely sufficient to surrogate the spinal cord dose tolerance for consistent treatment planning optimization and outcome analysis.

  View details for PubMedID 29988301

  View details for PubMedCentralID PMC6018048

• Hippocampus-Sparing Radiation and Chemotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollom, E., Soltys, S. G. 2018; 101 (3): 519–20

  View details for PubMedID 29893271

• CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center's experience JOURNAL OF NEURO-ONCOLOGY Sala, E., Moore, J. M., Amorin, A., Martinez, H., Bhowmik, A. C., Lamsam, L., Chang, S., Soltys, S. G., Katznelson, L., Harsh, G. R. 2018; 138 (2): 291–98

  Abstract

  Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5-50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6-84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.

  View details for PubMedID 29429125

• Radiation-Induced Edema After Single-Fraction or Multifraction Stereotactic Radiosurgery for Meningioma: A Critical Review INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Milano, M. T., Sharma, M., Soltys, S. G., Sahgal, A., Usuki, K. Y., Saenz, J., Grimm, J., El Naqa, I. 2018; 101 (2): 344–57

  Abstract

  Potential dosimetric and clinicopathologic predictors of radiation-induced brain edema after single-fraction or multifraction stereotactic radiosurgery (SRS) for non-base of skull (non-BOS) meningiomas are summarized based on a systematic review of the published literature.Reviewed studies (PubMed indexed from 1998 through 2017) included all or some non-BOS meningioma patients, reported risks of edema after SRS, and correlated dosimetric and/or nondosimetric measures with the magnitude of risk.Twenty-six studies reporting risks of edema after SRS for meningioma are reviewed. The treatment techniques as well as distribution of tumor locations, target dosing, and target volume varied across studies. Among 13 studies that included only non-BOS tumors or separately grouped non-BOS tumors, symptomatic edema occurred in 5% to 43% of patients and any edema occurred in 28% to 50%. The reported average time to onset of edema ranged from approximately 3 to 9 months in most studies. Factors reported to significantly correlate with increased risks of edema and/or symptomatic edema after SRS for meningioma include the following: greater tumor margin and/or maximum dose, greater tumor size and/or volume, non-BOS (particularly parasagittal) location, no prior resection for meningioma, and presence of pretreatment edema. Nevertheless, the extent and significance of these factors were inconsistent across studies. Potentially important dosimetric factors, such as volume of brain or tissue receiving single-fraction doses > 10 to 12 Gy, are not well studied.The variability in risks of edema and in factors impacting those risks is likely a result of differences across studies in the clinicopathologic characteristics of the patient populations, as well as differences in treatment modalities and SRS planning and delivery parameters. More studies on pooled populations, grouped by potential prognostic factors such as tumor location and prior therapy, are needed to better understand dosimetric and nondosimetric factors predictive of edema risk after SRS for meningioma.

  View details for PubMedID 29726362

• CXCR4 blockade at the end of irradiation to improve local control of glioblastoma (GBM). Thomas, R., Nagpal, S., Iv, M., Soltys, S. G., Bertrand, S., Pelpola, J., Yang, J., Ball, R. L., Brown, M., Recht, L. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.2019

  View details for Web of Science ID 000442916001230

• Timing, presentation, and patterns of failure of leptomeningeal disease after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis. Prabhu, R., Soltys, S. G., Turner, B. E., Marcrom, S., Fiveash, J. B., Foreman, P. M., Press, R. H., Patel, K. R., Curran, W., Breen, W., Brown, P. D., Jethwa, K., Grills, I. S., Arden, J., Foster, L. M., Manning, M. A., Stern, J. D., Asher, A. L., Burri, S. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.2070

  View details for Web of Science ID 000442916001279

• Brainstem Dose Constraints in Nonisometric Radiosurgical Treatment Planning of Trigeminal Neuralgia: A Single-Institution Experience WORLD NEUROSURGERY Zhang, M., Lamsam, L. A., Schoen, M. K., Mehta, S. S., Appelboom, G., Adler, J. K., Soltys, S. G., Chang, S. D. 2018; 113: E399–E407

  Abstract

  CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers nonisometric, conformational high-dose radiation to the trigeminal nerve with risk of subsequent hypoesthesia.We performed a retrospective, single-institution review of 66 patients with TGN treated with CyberKnife SRS to compare outcomes from 2 distinct treatment periods: standard dosing (n = 38) and reduced dosing (n = 28). Standard and reduced dosing permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a prescription dose of 60 Gy. Primary and secondary outcomes were Barrow Neurologic Institute pain and numbness scores. Maximum brainstem dose, prepontine nerve length, and treatment history were recorded for their predictive contributions by logistic regression.After matching, patients in the standard dosing and reduced dosing groups were followed for a median of 25 months and 19.5 months, respectively. Mean trigeminal nerve length was 8.55 mm in the standard dosing group and 9.46 mm in the reduced dosing group. Baseline rates of poorly controlled pain were 97% and 88%, respectively, which improved to 23.4% and 8.3%, respectively (P < 0.001 for both). The baseline rates of bothersome numbness were null in both groups, and increased to 25% in the standard group (P = 0.006) and to 21% in the reduced group (P = 0.07). Regression analyses suggested that reduced brainstem exposure (P = 0.01), as well as a longer trigeminal nerve (P = 0.01), were predictive of durable pain control.These outcomes demonstrate that a lower maximum brainstem dose can provide excellent pain control without affecting facial numbness. Longer nerves may achieve better long-term outcomes and help optimize individual plans.

  View details for PubMedID 29454124

• CyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing Disease WORLD NEUROSURGERY Moore, J. M., Sala, E., Amorin, A., Martinez, H., Bhowmik, A. C., Chang, S. D., Soltys, S. G., Harsh, G. R., Katznelson, L. 2018; 112: E425–E430

  Abstract

  Surgery is the primary treatment for Cushing disease. When surgery is unsuccessful in normalizing hypercortisolism, adjuvant radiation, such as stereotactic radiosurgery, may be useful to improve biochemical control.This retrospective study included a cohort of consecutive patients treated with CyberKnife (CK) radiosurgery for active Cushing disease at Stanford Hospital and Clinics.As first-line treatment, all patients underwent transsphenoidal surgery with histologic demonstration of an adrenocorticotropic hormone-producing pituitary adenoma. CK was performed as adjuvant therapy for persistent or recurrent disease. The median time between surgery and CK was 14 ± 34 months. Before CK, median maximal diameter of tumors was 9 mm (range, 7-32 mm), with cavernous sinus invasion in all patients (100%) and abutment of the optic chiasm in 1 patient (14.2%). With an average follow-up of 55.4 months, normalization of hypercortisolism was achieved in 4 patients (57.1%): 2 patients (28.5%) achieved normalization of the hypothalamic-pituitary-adrenal axis without glucocorticoid replacement, and 2 patients developed hypoadrenalism (28.5%). The median time to biochemical remission was 12.5 months. Hypopituitarism occurred in only 1 patient (14.2%), and no patients had visual complications. Time between surgery and radiotherapy of <14 months was associated with a significantly improved biochemical remission rate (P = 0.02).In a cohort of patients with Cushing disease, we demonstrate that CK is an effective treatment with rare complications.

  View details for PubMedID 29355797

• Survival Impact of Postoperative Radiotherapy Timing in Pediatric and Adolescent Medulloblastoma. Neuro-oncology Chin, A. L., Moding, E. J., Donaldson, S. S., Gibbs, I. C., Soltys, S. G., Hiniker, S. M., Pollom, E. L. 2018

  Abstract

  Radiation therapy (RT) remains a critical component of multimodality treatment for medulloblastoma. Traditionally, clinicians strive to start RT within 4-5 weeks of surgery, but the optimal timing after surgery remains unclear.Using the National Cancer Database, we identified pediatric and adolescent patients with medulloblastoma treated with curative-intent surgery, RT, and chemotherapy. Factors associated with early or delayed RT were identified using Pearson chi-squared tests. Overall survival (OS) differences based on RT timing were compared using the Kaplan-Meier estimator with log-rank tests. Patient, tumor, and treatment characteristics associated with OS were analyzed with univariate and multivariate Cox proportional hazard models.Among the 1338 patients analyzed, early RT (defined as initiation ≤3 weeks after surgery) was associated with younger age, M1-3 disease, and subtotal resection. Patients who initiated RT early had decreased five-year OS compared with patients who initiated RT 3.1-4, 4.1-5, or >5 weeks after surgery (72.5%, 80.5%, 79.4%, and 77.8%, respectively; p=0.019), but there was no significant difference in OS among the latter three groups (p=0.788). On multivariate analysis, early RT versus the 3.1-4-week interval was significantly associated with poorer OS (adjusted HR 1.72; 95% CI 1.19-2.48; p=0.004), while time to RT of >5 weeks but within 90 days of surgery did not adversely impact OS (p=0.563).In this large national database analysis, delaying RT within 90 days of surgery was not associated with inferior outcomes. Although clinical judgment remains paramount, postoperative RT timing should allow for healing and the development of an optimal treatment plan.

  View details for PubMedID 29309676

• Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma NEUROSURGERY Shah, J. L., Li, G., Shaffer, J. L., Azoulay, M. I., Gibbs, I. C., Nagpal, S., Soltys, S. G. 2018; 82 (1): 24-34

  View details for DOI 10.1093/neuros/nyx115

  View details for Web of Science ID 000424223500020

• Single- and Multi-Fraction Stereotactic Radiosurgery Dose Tolerances of the Optic Pathways. International journal of radiation oncology, biology, physics Milano, M. T., Grimm, J. n., Soltys, S. G., Yorke, E. n., Moiseenko, V. n., Tomé, W. A., Sahgal, A. n., Xue, J. n., Ma, L. n., Solberg, T. D., Kirkpatrick, J. P., Constine, L. S., Flickinger, J. C., Marks, L. B., El Naqa, I. n. 2018

  Abstract

  Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy.Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.

  View details for PubMedID 29534899

• Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study. The oncologist Xie, L. n., Nagpal, S. n., Wakelee, H. A., Li, G. n., Soltys, S. G., Neal, J. W. 2018

  Abstract

  Osimertinib is a third-generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first-line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone.Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups.The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression-free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5-11.8), 8.8 months (95% CI, 6.2-12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7-28.5), 7.7 months for group B (95% CI, 0-15.5), and 10.7 months for group C (95% CI, 9.0-12.5). The median PFS was 8.8 months for group A (95% CI, 4.3-13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6-11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups.Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation-related toxicity, delaying radiation could be considered for some patients with EGFR-mutant NSCLC with brain metastases who initially respond to osimertinib in the second-line setting.Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first-line treatment of EGFR-mutant non-small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.

  View details for PubMedID 30126856

• Preoperative Vs Postoperative Radiosurgery For Resected Brain Metastases: A Review. Neurosurgery Prabhu, R. S., Patel, K. R., Press, R. H., Soltys, S. G., Brown, P. D., Mehta, M. P., Asher, A. L., Burri, S. H. 2018

  Abstract

  Patients who undergo surgical resection of brain metastases are at significant risk of cavity local recurrence without additional radiation therapy. Postoperative stereotactic radiosurgery (SRS) is a method of focal treatment to the cavity to maximize local control while minimizing the risk of neurocognitive detriment associated with whole brain radiation therapy. Recently published randomized trials have demonstrated the benefit of postoperative SRS in terms of cavity tumor control and preserving neurocognition. However, there are several potential drawbacks with postoperative SRS including a possible increase in symptomatic radiation necrosis because of the need for cavity margin expansion due to target delineation uncertainty, the variable postoperative clinical course and potential delay in administering postoperative SRS, and the theoretical risk of tumor spillage into cerebrospinal fluid at the time of surgery. Preoperative SRS is an alternative paradigm wherein SRS is delivered prior to surgical resection, which may effectively address some of these potential drawbacks. The goal of this review is to examine the rationale, technique, outcomes, evidence, and future directions for the use of SRS as an adjunct to surgical resection. This can be delivered as either preoperative or postoperative SRS with potential advantages and disadvantages to both approaches that will be discussed.

  View details for PubMedID 29771381

• Stereotactic Radiosurgery for Skull Base Chordomas and Chondrosarcomas CHORDOMAS AND CHONDROSARCOMAS OF THE SKULL BASE AND SPINE, 2ND EDITION Shoo, B., Soltys, S. G., White, E., Fujimoto, D. K., Gibbs, I. C., Harsh, G. R., VazGuimaraes, F. 2018: 339–46

  View details for DOI 10.1016/B978-0-12-804257-1.00031-1

  View details for Web of Science ID 000426245100033

• Correlation between small-volume spinal cord doses for spine stereotactic body radiotherapy (SBRT) JOURNAL OF RADIOSURGERY AND SBRT Ma, L., Wang, L., Lee, Y., Tseng, C., Soltys, S., Braunstein, S., Sahgal, A. 2018; 5 (3): 229–36

  View details for Web of Science ID 000435021500007

• Clinical factors associated with mortality within three months after radiosurgery of asymptomatic brain metastases from non-small cell lung cancer. Journal of neuro-oncology Kakusa, B. n., Han, S. n., Aggarwal, S. n., Liu, B. n., Li, G. n., Soltys, S. n., Hayden Gephart, M. n. 2018

  Abstract

  Routine brain MRI surveillance frequently diagnoses small, asymptomatic brain metastases from non-small cell lung cancer (NSCLC) that are effectively treated with stereotactic radiosurgery (SRS). A subset of patients, however, may die prior to the onset of symptoms. This study identifies clinical features that distinguish neurologically-asymptomatic NSCLC brain metastases patients that die prior to routine 3 month follow-up after SRS.Retrospective chart review from 2007 to 2017 identified 18 patients with neurologically-asymptomatic NSCLC brain metastases who died < 3 months after SRS. Twenty-eight additional patients meeting criteria and surviving > 6 months after SRS were identified. Clinical factors were examined to determine characteristics correlated with survival using cox proportional hazards and nominal logistic regression models. Logistic regression models using salient factors were trained with 10-fold cross-validation and compared to the graded prognostic assessment (GPA) and score index of radiosurgery (SIR) using the AUC from receiver operant characteristic curves.The median survival following SRS was 1.4 and 9.2 months for the < 3 months and > 6 months groups, respectively. Age, number of brain metastases, and Karnofsky performance status were associated with overall survival while gender and interval between primary cancer and first brain metastasis diagnoses were associated with < 3 months and > 6 months survival, respectively. Models using GPA and SIR performed poorly compared to preliminary metrics generated in this study for prognosis of both < 3 months and > 6 months survival.Physicians require data to provide high-value, cost-conscious health care. Clinical metrics can screen patients with asymptomatic NSCLC brain metastases likely to die prior to the standard screening interval and observation could be considered.

  View details for PubMedID 30460628

• Newly diagnosed glioblastoma: adverse socioeconomic factors correlate with delay in radiotherapy initiation and worse overall survival. Journal of radiation research Pollom, E. L., Fujimoto, D. K., Han, S. S., Harris, J. P., Tharin, S. A., Soltys, S. G. 2018

  Abstract

  The optimal time for starting radiation in patients with glioblastoma (GBM) is controversial. We aimed to evaluate postoperative radiotherapy treatment patterns and the impact of timing of radiotherapy on survival outcomes in patients with GBM using a large, national hospital-based registry in the era of Stupp chemoradiation. We performed a retrospective cohort study using the National Cancer Data Base and identified adults with GBM diagnosed between 2010 and 2013 and treated with chemoradiation. We classified time from surgery/biopsy to radiation start into the following categories: <15 days, 15-21 days, 22-28 days, 29-35 days, 36-42 days and >42 days. We assessed the relation between time to radiation start and survival using Cox proportional hazards modeling adjusting for clinically relevant variables that were selected a priori. We used multivariate logistic modeling to determine factors independently associated with receipt of delayed radiation treatment. A total of 12 738 patients met our inclusion criteria after our cohort selection process. The majority of patients underwent either gross total (n = 5270, 41%) or subtotal (n = 4700, 37%) resection, while 2768 patients (22%) underwent biopsy only. Median time from definitive surgery or biopsy to initiation of radiation was 29 days (interquartile range 24-36 days). For patients who had biopsy or subtotal resection, earlier initiation of radiation did not appear to be associated with improved survival. However, among patients who underwent gross total resection, there appeared to be improved survival with early initiation of radiation. Patients who initiated radiation within 15-21 days of gross total resection had improved survival (hazard ratio 0.82, 95% confidence interval 0.69-0.98, P = 0.03) compared with patients who had delayed (>42 days after surgery) radiation. There was also a trend (P = 0.07 to 0.12) for improved survival for patients who initiated radiation within 22-35 days of gross total resection compared with patients who had delayed radiation. Patients who were black, had Medicaid or other government insurance or were not insured, and who lived in metropolitan areas or further away from the treating facility had higher odds of receiving radiation >35 days after gross total resection. Patients who lived in higher income areas had higher odds of receiving radiation within 35 days of a gross total resection. In a large cohort of patients with GBM treated with chemoradiation, our data suggest a survival benefit in initiating radiotherapy within 35 days after gross total resection. Further research is warranted to understand barriers to timely access to optimal therapy.

  View details for PubMedID 29432548

• A Phase 1/2 Trial of 5 Fraction Stereotactic Radiosurgery With 5 mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme: Pattern of Recurrence Analysis Azoulay, M., Gibbs, I. C., Hancock, S. L., Ho, C. K., Fujimoto, D. K., Chang, S. D., Harsh, G., Nagpal, S., Thomas, R., Recht, L., Choi, C. H., Soltys, S. G. ELSEVIER SCIENCE INC. 2017: S102–S103

  View details for DOI 10.1016/j.ijrobp.2017.06.245

  View details for Web of Science ID 000411559107036

• Stereotactic Radiosurgery for Benign Neurogenic Spinal Tumors Chin, A. L., Fujimoto, D. K., Tse, V., Chang, S. D., Adler, J. R., Gibbs, I. C., Dodd, R. L., Li, G., Gephart, M. H., Desai, A., Ratliff, J., Sachdev, S., Soltys, S. G. ELSEVIER SCIENCE INC. 2017: S186

  View details for DOI 10.1016/j.ijrobp.2017.06.464

  View details for Web of Science ID 000411559107212

• Stereotactic Radiosurgery for Spinal Metastases from Melanoma, Sarcoma, Renal Cell Carcinoma, and Hepatocellular Carcinoma Fujimoto, D. K., Kumar, K. A., White, E. C., Ho, C. K., Azoulay, M., Aggarwal, S., Pradhan, P., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Choi, C. H., Soltys, S. G. ELSEVIER SCIENCE INC. 2017: E73

  View details for DOI 10.1016/j.ijrobp.2017.06.766

  View details for Web of Science ID 000411559100172

• Spine Stereotactic Radiosurgery: Outcomes and Predictors of Local Recurrence Kumar, K. A., Fujimoto, D. K., White, E. C., Ho, C. K., Azoulay, M., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Desai, A., Ratliff, J., Soltys, S. G., Choi, C. H. ELSEVIER SCIENCE INC. 2017: E86

  View details for DOI 10.1016/j.ijrobp.2017.06.796

  View details for Web of Science ID 000411559100201

• Newly Diagnosed Glioblastoma: Delay in Radiation Therapy Initiation Associated With Adverse Socioeconomic Factors and Worse Survival Pollom, E., Fujimoto, D. K., Harris, J. P., Chin, A. L., Qian, Y., Tharin, S., Soltys, S. G. ELSEVIER SCIENCE INC. 2017: E100

  View details for DOI 10.1016/j.ijrobp.2017.06.830

  View details for Web of Science ID 000411559100235

• Cost-Effectiveness of Radiation and Chemotherapy for High-Risk Low Grade Glioma Qian, Y., Maruyama, S., Kim, H., Pollom, E., Kumar, K. A., Harris, J. P., Chin, A. L., Pitt, A., Bendavid, E., Owens, D., Durkee, B. Y., Soltys, S. G. ELSEVIER SCIENCE INC. 2017: S37

  View details for DOI 10.1016/j.ijrobp.2017.06.098

  View details for Web of Science ID 000411559106163

• Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results. International journal of radiation oncology, biology, physics Pollom, E. L., Fujimoto, D., Wynne, J., Seiger, K., Modlin, L. A., Jacobs, L. R., Azoulay, M., von Eyben, R., Tupper, L., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Harraher, C., Nagpal, S., Thomas, R. P., Recht, L. D., Choi, C. Y., Soltys, S. G. 2017; 98 (1): 123-130

  Abstract

  We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide.HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point.With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01).On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.

  View details for DOI 10.1016/j.ijrobp.2017.01.242

  View details for PubMedID 28586949

• The radiosurgery fractionation quandary: single fraction or hypofractionation? NEURO-ONCOLOGY Kirkpatrick, J. P., Soltys, S. G., Lo, S. S., Beal, K., Shrieve, D. C., Brown, P. D. 2017; 19: 38-49

  Abstract

  Stereotactic radiosurgery (SRS), typically administered in a single session, is widely employed to safely, efficiently, and effectively treat small intracranial lesions. However, for large lesions or those in close proximity to critical structures, it can be difficult to obtain an acceptable balance of tumor control while avoiding damage to normal tissue when single-fraction SRS is utilized. Treating a lesion in 2 to 5 fractions of SRS (termed "hypofractionated SRS" [HF-SRS]) potentially provides the ability to treat a lesion with a total dose of radiation that provides both adequate tumor control and acceptable toxicity. Indeed, studies of HF-SRS in large brain metastases, vestibular schwannomas, meningiomas, and gliomas suggest that a superior balance of tumor control and toxicity is observed compared with single-fraction SRS. Nonetheless, a great deal of effort remains to understand radiobiologic mechanisms for HF-SRS driving the dose-volume response relationship for tumors and normal tissues and to utilize this fundamental knowledge and the results of clinic studies to optimize HF-SRS. In particular, the application of HF-SRS in the setting of immunomodulatory cancer therapies offers special challenges and opportunities.

  View details for DOI 10.1093/neuonc/now301

  View details for Web of Science ID 000400895800005

  View details for PubMedCentralID PMC5463582

• Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: results of an international survey. Journal of neurosurgery. Spine Redmond, K. J., Lo, S. S., Soltys, S. G., Yamada, Y., Barani, I. J., Brown, P. D., Chang, E. L., Gerszten, P. C., Chao, S. T., Amdur, R. J., De Salles, A. A., Guckenberger, M., Teh, B. S., Sheehan, J., Kersh, C. R., Fehlings, M. G., Sohn, M., Chang, U., Ryu, S., Gibbs, I. C., Sahgal, A. 2017; 26 (3): 299-306

  Abstract

  OBJECTIVE Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases. METHODS Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice. Responses were defined as follows: 1) consensus: selected by ≥ 75% of respondents; 2) predominant: selected by 50% of respondents or more; and 3) controversial: no single response selected by a majority of respondents. RESULTS Consensus treatment indications included: radioresistant primary, 1-2 levels of adjacent disease, and previous radiation therapy. Contraindications included: involvement of more than 3 contiguous vertebral bodies, ASIA Grade A status (complete spinal cord injury without preservation of motor or sensory function), and postoperative Bilsky Grade 3 residual (cord compression without any CSF around the cord). For treatment planning, co-registration of the preoperative MRI and postoperative T1-weighted MRI (with or without gadolinium) and delineation of the cord on the T2-weighted MRI (and/or CT myelogram in cases of significant hardware artifact) were predominant. Consensus GTV (gross tumor volume) was the postoperative residual tumor based on MRI. Predominant CTV (clinical tumor volume) practice was to include the postoperative bed defined as the entire extent of preoperative tumor, the relevant anatomical compartment and any residual disease. Consensus was achieved with respect to not including the surgical hardware and incision in the CTV. PTV (planning tumor volume) expansion was controversial, ranging from 0 to 2 mm. The spinal cord avoidance structure was predominantly the true cord. Circumferential treatment of the epidural space and margin for paraspinal extension was controversial. Prescription doses and spinal cord tolerances based on clinical scenario, neurological compromise, and prior overlapping treatments were controversial, but reasonable ranges are presented. Fifty percent of those surveyed practiced an integrated boost to areas of residual tumor and density override for hardware within the beam path. Acceptable PTV coverage was controversial, but consensus was achieved with respect to compromising coverage to meet cord constraint and fractionation to improve coverage while meeting cord constraint. CONCLUSIONS The consensus by spinal radiosurgery experts suggests that postoperative SBRT is indicated for radioresistant primary lesions, disease confined to 1-2 vertebral levels, and/or prior overlapping radiotherapy. The GTV is the postoperative residual tumor, and the CTV is the postoperative bed defined as the entire extent of preoperative tumor and anatomical compartment plus residual disease. Hardware and scar do not need to be included in CTV. While predominant agreement was reached about treatment planning and definition of organs at risk, future investigation will be critical in better understanding areas of controversy, including whether circumferential treatment of the epidural space is necessary, management of paraspinal extension, and the optimal dose fractionation schedules.

  View details for DOI 10.3171/2016.8.SPINE16121

  View details for PubMedID 27834628

• Cost-Effectiveness of Radiation and Chemotherapy for High-Risk Low-Grade Glioma. Neuro-oncology Qian, Y. n., Maruyama, S. n., Kim, H. n., Pollom, E. L., Kumar, K. A., Chin, A. L., Harris, J. P., Chang, D. T., Pitt, A. n., Bendavid, E. n., Owens, D. K., Durkee, B. Y., Soltys, S. G. 2017

  Abstract

  The addition of PCV (procarbazine, lomustine, vincristine) chemotherapy to radiotherapy (RT) for patients with high-risk (≥ 40 years old or sub-totally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy.A decision tree with an integrated three-state Markov model was created to follow patients with high risk LGG after surgery treated with RT vs. RT+PCV. Patients existed in one of 3 health states: stable, progressive, and dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the healthcare perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters.Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs. 5.17 for RT alone) at an incremental cost of $48,635 ($188,234 for RT+PCV vs. $139,598 for RT alone), resulting in an incremental cost-effectiveness ratio of $10,186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of $100,000 per QALY.The addition of PCV to RT is a cost-effective treatment strategy for patients with high-risk LGG.

  View details for PubMedID 28666368

• A Phase II Study of Etirinotecan Pegol (NKTR-102) in Patients with Refractory Brain Metastases and Advanced Lung Cancer Nagpal, S., Wakelee, H., Padda, S., Bertrand, S., Acevedo, B., Tisch, A., Pagtama, J., Soltys, S., Neal, J. ELSEVIER SCIENCE INC. 2017: S940

  View details for Web of Science ID 000413055802110

• Imaging changes over 18 months following stereotactic radiosurgery for brain metastases: both late radiation necrosis and tumor progression can occur. Journal of neuro-oncology Fujimoto, D. n., von Eyben, R. n., Gibbs, I. C., Chang, S. D., Li, G. n., Harsh, G. R., Hancock, S. n., Fischbein, N. n., Soltys, S. G. 2017

  Abstract

  Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11 months. Similarly, the risk of local tumor recurrence following SRS is < 5% after 18 months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as > 18 months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement > 18 months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2 months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9 months (range 18.5-63.2 months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2 months and 7 lesions had late LF occurring a median of 23.6 months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3 years and local failure up to 3.8 years following SRS in our cohort.

  View details for PubMedID 29098569

• Consensus Contouring Guidelines for Postoperative Completely Resected Cavity Stereotactic Radiosurgery for Brain Metastases. International journal of radiation oncology, biology, physics Soliman, H. n., Ruschin, M. n., Angelov, L. n., Brown, P. D., Chiang, V. L., Kirkpatrick, J. P., Lo, S. S., Mahajan, A. n., Oh, K. S., Sheehan, J. P., Soltys, S. G., Sahgal, A. n. 2017

  Abstract

  To propose contouring guidelines based on consensus contours generated by 10 international experts for cavity stereotactic radiosurgery (SRS), an emerging treatment option after surgical resection of brain metastases. No guidelines for contouring the surgical cavity volume have been previously reported.Ten postoperative completely resected cases with varying clinical scenarios and locations within the brain were selected. For each case, 10 experts independently contoured the surgical cavity clinical target volume (CTV). All the contours were analyzed, and agreement was calculated using the simultaneous truth and performance level estimation (STAPLE) with the kappa statistic. A follow-up survey was also completed by each investigator to summarize their contouring rationale for a number of different clinical scenarios. The results from the survey and the consensus STAPLE contours were both summarized to establish contouring guidelines.A high level of agreement was found between the expert CTV contours (mean sensitivity 0.75, mean specificity 0.98), and the mean kappa was 0.65. The agreement was statistically significant at P<.001 for all cases. From these results and analyses of the survey answers, the recommendations for CTV include fusion of the preoperative magnetic resonance imaging scan to aid in volume delineation; contouring the entire surgical tract regardless of the preoperative location of the tumor; extension of the CTV 5 to 10 mm along the dura overlying the bone flap to account for microscopic disease extension in cases with preoperative dural contact; and a margin of ≤5 mm into the adjacent sinus when preoperative venous sinus contact was present.Consensus contouring guidelines for postoperative completely resected cavity SRS treatment were established using expert contours and clinical practice. However, in the absence of clinical data supporting these recommendations, these guidelines serve as a baseline for further study and refinement.

  View details for PubMedID 29157748

• New Hypofractionation Radiation Strategies for Glioblastoma. Current oncology reports Azoulay, M. n., Shah, J. n., Pollom, E. n., Soltys, S. G. 2017; 19 (9): 58

  Abstract

  Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with a median survival of less than 2 years despite the standard of care treatment of 6 weeks of chemoradiotherapy. We review the data investigating hypofractionated radiotherapy (HFRT) in the treatment of newly diagnosed GBM.Investigators have explored alternative radiotherapy strategies that shorten treatment duration with the goal of similar or improved survival while minimizing toxicity. HFRT over 1-3 weeks is already a standard of care for patients with advanced age or poor performance status. For young patients with good performance status, HFRT holds the promise of radiobiologically escalating the dose and potentially improving local control while maintaining quality of life. Through the use of shorter radiotherapy fractionation regimens coupled with novel systemic agents, improved outcomes for patients with GBM may be achieved.

  View details for PubMedID 28735440

• Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial. International journal of radiation oncology, biology, physics Choi, C. Y., Wakelee, H. A., Neal, J. W., Pinder-Schenck, M. C., Yu, H. M., Chang, S. D., Adler, J. R., Modlin, L. A., Harsh, G. R., Soltys, S. G. 2017; 99 (1): 16–21

  Abstract

  To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates.In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days.From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS.The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases.

  View details for PubMedID 28816142

• Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Redmond, K. J., Robertson, S., Lo, S. S., Soltys, S. G., Ryu, S., McNutt, T., Chao, S. T., Yamada, Y., Ghia, A., Chang, E. L., Sheehan, J., Sahgal, A. 2017; 97 (1): 64-74

  Abstract

  To develop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases.Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV) for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimized confidence level consensus contours using histogram agreement analyses.Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (P<.001 for all cases). Optimized consensus contours were established for all patients with 80% confidence interval. Recommendations for CTV include treatment of the entire preoperative extent of bony and epidural disease, plus immediately adjacent bony anatomic compartments at risk of microscopic disease extension. In particular, a "donut-shaped" CTV was consistently applied in cases of preoperative circumferential epidural extension, regardless of extent of residual epidural extension. Otherwise more conformal anatomic-based CTVs were determined and described. Spinal instrumentation was consistently excluded from the CTV.We provide consensus contouring guidelines for common scenarios in postoperative SBRT for spinal metastases. These consensus guidelines are subject to clinical validation.

  View details for DOI 10.1016/j.ijrobp.2016.09.014

  View details for PubMedID 27843035

• Ablative Radiotherapy as a Noninvasive Alternative to Catheter Ablation for Cardiac Arrhythmias. Current cardiology reports Zei, P. C., Soltys, S. n. 2017; 19 (9): 79

  Abstract

  Stereotactic radioablation is a commonly utilized technology to noninvasively treat solid tumors with precision and efficacy. Using a robotic arm mounted delivery system, multiple low-dose ionizing radiation beams are delivered from multiple angles, concentrating ablative energy at the target tissue. Recently, this technology has been evaluated for treatment of cardiac arrhythmias. This review will present the basic underlying principles, proof-of-principle studies, and clinical experience with stereotactic arrhythmia radioablation.Most recently, stereotactic radioablation has been used to safely and effectively treat a limited number of patients with malignant arrhythmias, including ventricular tachycardia (VT) and atrial fibrillation (AF). Treatment protocols, outcomes, ongoing studies, and future directions will be discussed. Stereotactic radioablation is a well-established technology that has been shown to be a safe and effective therapy for patients with drug-refractory cardiac arrhythmias, including VT and AF. Further clinical evaluation to define safety and efficacy in larger populations of patients is needed.

  View details for PubMedID 28752279

  View details for PubMedCentralID PMC5532420

• Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma. Neurosurgery Shah, J. L., Li, G. n., Shaffer, J. L., Azoulay, M. I., Gibbs, I. C., Nagpal, S. n., Soltys, S. G. 2017

  Abstract

  Glioblastoma is the most common primary brain tumor in adults. Standard therapy depends on patient age and performance status but principally involves surgical resection followed by a 6-wk course of radiation therapy given concurrently with temozolomide chemotherapy. Despite such treatment, prognosis remains poor, with a median survival of 16 mo. Challenges in achieving local control, maintaining quality of life, and limiting toxicity plague treatment strategies for this disease. Radiotherapy dose intensification through hypofractionation and stereotactic radiosurgery is a promising strategy that has been explored to meet these challenges. We review the use of hypofractionated radiotherapy and stereotactic radiosurgery for patients with newly diagnosed and recurrent glioblastoma.

  View details for PubMedID 28605463

• Image-guided stereotactic radiosurgery for treatment of spinal hemangioblastoma NEUROSURGICAL FOCUS Pan, J., Ho, A. L., D'Astous, M., Sussman, E. S., Thompson, P. A., Tayag, A. T., Pangilinan, L., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2017; 42 (1)

  Abstract

  OBJECTIVE Stereotactic radiosurgery (SRS) has been an attractive treatment option for hemangioblastomas, especially for lesions that are surgically inaccessible and in patients with von Hippel-Lindau (VHL) disease and multiple lesions. Although there has been a multitude of studies examining the utility of SRS in intracranial hemangioblastomas, SRS has only recently been used for spinal hemangioblastomas due to technical limitations. The purpose of this study is to provide a long-term evaluation of the effectiveness of image-guided radiosurgery in halting tumor progression and providing symptomatic relief for spinal hemangioblastomas. METHODS Between 2001 and 2011, 46 spinal hemangioblastomas in 28 patients were treated using the CyberKnife image-guided radiosurgery system at the authors' institution. Fourteen of these patients also had VHL disease. The median age at treatment was 43.5 years (range 19-85 years). The mean prescription radiation dose to the tumor periphery was 21.6 Gy (range 15-35 Gy). The median tumor volume was 0.264 cm(3) (range 0.025-70.9 cm(3)). Tumor response was evaluated on serial, contrast-enhanced CT and MR images. Clinical response was evaluated by clinical and imaging evaluation. RESULTS The mean follow-up for the cohort was 54.3 months. Radiographic follow-up was available for 19 patients with 34 tumors; 32 (94.1%) tumors were radiographically stable or displayed signs of regression. Actuarial control rates at 1, 3, and 5 years were 96.1%, 92.3%, and 92.3%, respectively. Clinical evaluation on follow-up was available for 13 patients with 16 tumors; 13 (81.2%) tumors in 10 patients had symptomatic improvement. No patient developed any complications related to radiosurgery. CONCLUSIONS Image-guided SRS is safe and effective for the primary treatment of spinal hemangioblastomas and is an attractive alternative to resection, especially for those with VHL disease.

  View details for DOI 10.3171/2016.10.FOCUS16361

  View details for Web of Science ID 000392113200012

  View details for PubMedID 28041328

• Stereotactic radiosurgery for non-vestibular cranial nerve schwanommas JOURNAL OF NEURO-ONCOLOGY D'Astous, M., Ho, A. L., Pendharkar, A., Choi, C. Y., Soltys, S. G., Gibbs, I. C., Tayag, A. T., Thompson, P. A., Adler, J. R., Chang, S. D. 2017; 131 (1): 177-183

  Abstract

  Non-vestibular cranial nerve schwannomas (NVCNS) are rare lesions, representing <10 % of cranial nerve schwannomas. The optimal treatment for NVCNS is often derived from vestibular schwannomas experience. Surgical resection has been referred to as the first line treatment for those benign tumors, but significant complication rates are reported. Stereotactic radiosurgery (SRS) has arisen as a mainstay of treatment for many benign tumors, including schwanommas. We retrospectively reviewed the outcomes of NVCNS treated by SRS to characterize tumor control, symptom relief, toxicity, and the role of hypo-fractionation of SRS dose. Eighty-eight (88) patients, with ninety-five (95) NVCNS were treated with either single or multi-session SRS from 2001 to 2014. Local control was achieved in 94 % of patients treated (median follow-up of 33 months, range 1-155). Complications were seen in 7.4 % of cases treated with SRS. At 1-year, 57 % of patients had improvement or resolution of their symptoms, while 35 % were stable and 8 % had worsening or increased symptoms. While 42 % received only one session, results on local control were similar for one or multiple sessions (p = 0.424). SRS for NVCNS is a treatment modality that provides excellent local control with minimal complication risk compared to traditional neurosurgical techniques. Tumor control obtained with a multi-session treatment was not significantly different from single session treatment. Safety profile was also comparable for uni or multi-session treatments. We concluded that, as seen in VS treated with CK SRS, radiosurgery treatment can be safely delivered in cases of NVCNS.

  View details for DOI 10.1007/s11060-016-2286-7

  View details for Web of Science ID 000393065400019

• Brain Metastases From Melanoma: Therapy at the Crossroads INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Kirkpatrick, J. P., Laack, N. N., Soltys, S. G., Halasz, L. M., Breneman, J. C., Shih, H. A. 2016; 96 (4): 713-716

  View details for DOI 10.1016/j.ijrobp.2016.06.005

  View details for Web of Science ID 000385524000001

  View details for PubMedID 27788943

• Physician Assessment Versus the Graded Prognostic Assessment (GPA) for Brain Metastases Aggarwal, S., Prionas, N. D., Carter, J. N., Pradhan, P., Bui, J. L., Fujimoto, D. K., von Eyben, R., Koong, A. C., Chang, D. T., Ho, C. K., Soltys, S. G. ELSEVIER SCIENCE INC. 2016: E126

  View details for DOI 10.1016/j.ijrobp.2016.06.908

  View details for Web of Science ID 000387655802307

• Stereotactic Radiosurgery for Newly Diagnosed and Recurrent Chordomas White, E. C., Ajlan, A. C., Kumar, K. A., Gibbs, I. C., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G. ELSEVIER SCIENCE INC. 2016: E89

  View details for DOI 10.1016/j.ijrobp.2016.06.815

  View details for Web of Science ID 000387655802217

• Accuracy of Predicting Survival Outcomes in Palliative Radiation Therapy Patients Aggarwal, S., Prionas, N. D., Carter, J. N., Pradhan, P., Bui, J. L., von Eyben, R., Ho, C. K., Hancock, S. L., Soltys, S. G., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2016: S148–S149

  View details for DOI 10.1016/j.ijrobp.2016.06.360

  View details for Web of Science ID 000387655804673

• New Enhancement Over 18 Months Following Stereotactic Radiosurgery for Brain Metastases: Both Radiation Necrosis and Tumor Failure Can Occur Fujimoto, D. K., von Eyben, R., Li, G., Chang, S. D., Fischbein, N., Harsh, G. R., Hancock, S. L., Gibbs, I. C., Soltys, S. G. ELSEVIER SCIENCE INC. 2016: E129

  View details for DOI 10.1016/j.ijrobp.2016.06.915

  View details for Web of Science ID 000387655802314

• Spinal Stereotactic Radiosurgery: Comparison of Targeting the Gross Tumor Volume Alone Versus With the Adjacent Vertebral Segment Kumar, K. A., White, E. C., Ho, C. K., Azoulay, M., Fujimoto, D. K., Aggarwal, S., Gibbs, I. C., Adler, J. R., Hancock, S. L., Choi, C. H., Soltys, S. G. ELSEVIER SCIENCE INC. 2016: S175

  View details for DOI 10.1016/j.ijrobp.2016.06.440

  View details for Web of Science ID 000387655805031

• The Outcome of Hypofractionated Stereotactic Radiosurgery for Large Vestibular Schwannomas. World neurosurgery Teo, M., Zhang, M., Li, A., Thompson, P. A., Tayag, A. T., Wallach, J., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Chang, S. D. 2016; 93: 398-409

  Abstract

  Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypofractionated SRS for VS > 3 cm.A total of 587 patients with VS treated with SRS between 1998 and 2014 were reviewed retrospectively, and 30 Koos grade IV VSs were identified. There were 6 patients with neurofibromatosis 2 (NF2), 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with >3 cm after previous resection. Patients were treated by a median of 3 fractions at 18 Gy.After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80%, respectively, with 20% requiring salvage treatment. For patients who had previous tumor resection rather than primary CK, the estimates were 46% and 5%, respectively, with progression, and 3-year control rates of 71% and 94% (P = 0.008). Tumor control was also lower among NF2 versus non-NF2 patients (40% vs. 95%; P = 0.0014). Among patients with good clinical baselines before CK, 88% were functionally independent (modified Rankin Scale score, 0-2), 88% had good facial function (House-Brackmann grade I-II), and 38% had serviceable hearing (Gardner-Robertson grade I-II) at last follow-up. Hearing worsening was more likely among patients treated with primary CK (33% vs. 90%; P = 0.04).Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow-up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favorable functional outcomes.

  View details for DOI 10.1016/j.wneu.2016.06.080

  View details for PubMedID 27368508

• RESULTS OF A PHASE I/II TRIAL OF 5 FRACTION STEREOTACTIC RADIOSURGERY WITH CONCURRENT AND ADJUVANT TEMOZOLOMIDE IN NEWLY DIAGNOSED SUPRATENTORIAL GLIOBLASTOMA MULTIFORME Azoulay, M., Fujimoto, D., Modlin, L., Ho, C., Gibbs, I., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Harraher, C., Nagpal, S., Thomas, R., Vrecht, L., Choi, C., Soltys, S. G. ELSEVIER IRELAND LTD. 2016: S14

  View details for Web of Science ID 000970253300038

• CyberKnife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas. World neurosurgery Zhang, M., Ho, A. L., D'Astous, M., Pendharkar, A. V., Choi, C. Y., Thompson, P. A., Tayag, A. T., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 91: 574-581 e1

  Abstract

  Recurrent World Health Organization (WHO) grade II and III meningiomas have traditionally been treated by surgery alone, but early literature suggests that adjuvant stereotactic radiosurgery may greatly improve outcomes. We present the long-term tumor control and safety of a hypofractionated stereotactic radiosurgery regimen.Prospectively collected data of 44 WHO grade II and 9 WHO grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy were reviewed. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.For WHO grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58%, and 36%. For WHO grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation naïve and experienced patients were 48% and 0% (P = 0.14). Overall, 7 of 44 grade II patients and 8 of 9 grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for grade II and III meningiomas were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.Stereotactic radiosurgery for adjuvant and salvage treatment of WHO grade II meningioma using a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future studies should focus on radiation-naïve patients and local management of malignant meningioma.

  View details for DOI 10.1016/j.wneu.2016.04.019

  View details for PubMedID 27108030

• Stereotactic radiosurgery for intramedullary spinal arteriovenous malformations JOURNAL OF CLINICAL NEUROSCIENCE Kalani, M. A., Choudhri, O., Gibbs, I. C., Soltys, S. G., Adler, J. R., Thompson, P. A., Tayag, A. T., Samos, C. H., Chang, S. D. 2016; 29: 162-167

  Abstract

  Spinal cord arteriovenous malformations (AVM) are rare lesions associated with recurrent hemorrhage and progressive ischemia. Occasionally a favorable location, size or vascular anatomy may allow management with endovascular embolization and/or microsurgical resection. For most, however, there is no good treatment option. Between 1997 and 2014, we treated 37 patients (19 females, 18 males, median age 30years) at our institution diagnosed with intramedullary spinal cord AVM (19 cervical, 12 thoracic, and six conus medullaris) with CyberKnife (Accuray, Sunnyvale, CA, USA) stereotactic radiosurgery. A history of hemorrhage was present in 50% of patients. The mean AVM volume of 2.3cc was treated with a mean marginal dose of 20.5Gy in a median of two sessions. Clinical and MRI follow-up were carried out annually, and spinal angiography was repeated at 3years. We report an overall obliteration rate of 19% without any post-treatment hemorrhagic events. In those AVM that did not undergo obliteration, significant volume reduction was noted at 3years. Although the treatment paradigm for spinal cord AVM continues to evolve, radiosurgical treatment is capable of safely obliterating or significantly shrinking most intramedullary spinal cord AVM.

  View details for DOI 10.1016/j.jocn.2015.12.005

  View details for Web of Science ID 000378449800032

  View details for PubMedID 26869363

• The Parotid Gland is an Underrecognized Organ at Risk for Craniospinal Irradiation TECHNOLOGY IN CANCER RESEARCH & TREATMENT King, M. T., Modlin, L., Million, L., Donaldson, S. S., Gibbs, I. C., Choi, C. Y., Soltys, S. G. 2016; 15 (3): 472-479

  Abstract

  Current craniospinal irradiation (CSI) protocols do not include the parotid gland as an organ at risk, potentially leading to late effects of xerostomia and secondary parotid malignancies. We analyzed the effect of CSI treatment parameters on parotid dose.We retrospectively reviewed 50 consecutive patients treated with CSI to an intracranial dose >26 Gy. Parotid dose was compared to a Radiation Therapy Oncology Group (RTOG) dose constraint (at least 1 parotid with mean dose <26 Gy). The effects of CSI dose (≤24 Gy vs 24 Gy), volumetric-modulated arc therapy (VMAT) versus 3-dimensional (3D) CSI technique, boost dose (≤24 Gy vs 24 Gy), supratentorial versus infratentorial boost location, intensity-modulated radiation therapy (IMRT)-based versus 3D boost technique, supine versus prone position, and age on parotid dose were analyzed using multivariate regression analysis.The RTOG parotid dose constraint was exceeded in 22 (44%) of 50 patients. On multivariate regression analysis, lower CSI dose and VMAT CSI technique were associated with reduced parotid dose for the CSI fields. For the boost fields, lower boost dose and supratentorial boost location were associated with lower parotid dose. All 5 patients who underwent VMAT CSI met dose constraints. Furthermore, for infratentorial lesions with a total (CSI plus boost) dose prescription dose >50 Gy (n = 24), 11 of 16 patients who received low-dose CSI (18-23.4 Gy) were able to meet dose constraints, when compared to only 2 of 8 patients who received high dose CSI (36 Gy).Given the large number of patients exceeding the parotid dose constraint, the parotid gland should be considered an organ at risk. CSI dose de-escalation and IMRT-based CSI techniques may minimize the risk of xerostomia.

  View details for DOI 10.1177/1533034615583406

  View details for Web of Science ID 000375704500008

  View details for PubMedID 25948323

• A phase I study of chemo-radiotherapy with plerixafor for newly diagnosed glioblastoma (GB). Thomas, R., Nagpal, S., Iv, M., Soltys, S. G., Corbin, Z., Xu, L., Recht, C., Bertrand, S., Jain, V., Acevedo, B., Brown, M., Recht, L. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.2068

  View details for Web of Science ID 000404665403055

• Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery. Seminars in radiation oncology Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

  Abstract

  Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

  View details for DOI 10.1016/j.semradonc.2015.11.008

  View details for PubMedID 27000505

• Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery SEMINARS IN RADIATION ONCOLOGY Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

  Abstract

  Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

  View details for DOI 10.1016/j.semradonc.2015.11.008

  View details for Web of Science ID 000373242700003

• Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord. Seminars in radiation oncology Grimm, J., Sahgal, A., Soltys, S. G., Luxton, G., Patel, A., Herbert, S., Xue, J., Ma, L., Yorke, E., Adler, J. R., Gibbs, I. C. 2016; 26 (2): 165-171

  Abstract

  A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation.

  View details for DOI 10.1016/j.semradonc.2015.11.010

  View details for PubMedID 27000514

• CyberKnife radiosurgery for brainstem metastases: Management and outcomes and a review of the literature. Journal of clinical neuroscience Liu, S., Murovic, J., Wallach, J., Cui, G., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 25: 105-110

  Abstract

  To our knowledge this paper is the first to use recursive partitioning analysis (RPA) for brainstem metastasis (BSM) patient outcomes, after CyberKnife radiosurgery (CKRS; Accuray, Sunnyvale, CA, USA); nine similar previous publications used mainly Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden). Retrospective chart reviews from 2006-2013 of 949 CKRS-treated brain metastasis patients showed 54BSM patients (5.7%): 35 RPA Class II (65%) and 19 Class III (35%). There were 30 women (56%) and 24 men (44%). The median age was 59years (range 36-80) and median follow-up was 5months (range 1-52). Twenty-three patients (43%) had lung carcinoma BSM and 12 (22%) had breast cancer BSM. Fifty-four RPA Class II and III BSM patients had a median overall survival (OS) of 5months, and for each Class 8 and 2months, respectively. Of 36 RPA Class II and III patients with available symptoms (n=31) and findings (n=33), improvement/stability occurred in the majority for symptoms (86%) and findings (92%). Of 35 cases, 28 (80%) achieved BSM local control (LC); 13/14 with breast histology (93%) and 10/13 with lung histology (77%). All six RPA Class II and III patients with controlled extracranial systemic disease (ESD) experienced LC. Median tumor volume was 0.14cm(3); of 34 RPA Class II and III cases, 26 LC patients had a 0,13cm(3) median tumor volume while it was 0.27cm(3) in the eight local failures. Of 35 cases, single session equivalent dosages less than the median (n=13), at the 17.9Gy median (n=5) and greater than the median (n=17) had BSM LC in 10 (77%), four (80%) and 14 cases (82%), respectively. Univariate analysis showed Karnofsky Performance Score, RPA Class and ESD-control predicted OS. CKRS is useful for RPA Class II and III BSM patients with effective clinical and local BSM control.

  View details for DOI 10.1016/j.jocn.2015.10.013

  View details for PubMedID 26778047

• Stereotactic Arrhythmia Radioablation (STAR) of Ventricular Tachycardia: A Treatment Planning Study. Cure¯us Wang, L., Fahimian, B., Soltys, S. G., Zei, P., Lo, A., Gardner, E. A., Maguire, P. J., Loo, B. W. 2016; 8 (7)

  Abstract

  The first stereotactic arrhythmia radioablation (STAR) of ventricular tachycardia (VT) was delivered at Stanford on a robotic radiosurgery system (CyberKnife® G4) in 2012. The results warranted further investigation of this treatment. Here we compare dosimetrically three possible treatment delivery platforms for STAR.The anatomy and target volume of the first treated patient were used for this study. A dose of 25 Gy in one fraction was prescribed to the planning target volume (PTV). Treatment plans were created on three treatment platforms: CyberKnife® G4 system with Iris collimator (Multiplan, V. 4.6)(Plan #1), CyberKnife® M6 system with InCise 2(TM) multileaf collimator (Multiplan V. 5.3)(Plan #2) and Varian TrueBeam(TM) STx with HD 120(TM) MLC and 10MV flattening filter free (FFF) beam (Eclipse planning system, V.11) (Plan #3 coplanar and #4 noncoplanar VMAT plans). The four plans were compared by prescription isodose line, plan conformity index, dose gradient, as well as dose to the nearby critical structures. To assess the delivery efficiency, planned monitor units (MU) and estimated treatment time were evaluated.Plans #1-4 delivered 25 Gy to the PTV to the 75.0%, 83.0%, 84.3%, and 84.9% isodose lines and with conformity indices of 1.19, 1.16, 1.05, and 1.05, respectively. The dose gradients for plans #1-4 were 3.62, 3.42, 3.93, and 3.73 with the CyberKnife® MLC plan (Plan #2) the best, and the TrueBeam(TM) STx co-planar plan (Plan #3) the worst. The dose to nearby critical structures (lung, stomach, bowel, and esophagus) were all well within tolerance. The MUs for plans #1-4 were 27671, 16522, 6275, and 6004 for an estimated total-treatment-time/beam-delivery-time of 99/69, 65/35, 37/7, and 56/6 minutes, respectively, under the assumption of 30 minutes pretreatment setup time. For VMAT gated delivery, a 40% duty cycle, 2400MU/minute dose rate, and an extra 10 minutes per extra arc were assumed.Clinically acceptable plans were created with all three platforms. Plans with MLC were considerably more efficient in MU. CyberKnife® M6 with InCise 2(TM) collimator provided the most conformal plan (steepest dose drop-off) with significantly reduced MU and treatment time. VMAT plans were most efficient in MU and delivery time. Fluoroscopic image guidance removes the need for additional fiducial marker placement; however, benefits may be moderated by worse dose gradient and more operator-dependent motion management by gated delivery.

  View details for DOI 10.7759/cureus.694

  View details for PubMedID 27570715

  View details for PubMedCentralID PMC4996541

• Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS Blanck, O., Wang, L., Baus, W., Grimm, J., Lacornerie, T., Nilsson, J., Luchkovskyi, S., Palazon Cano, I., Shou, Z., Ayadi, M., Treuer, H., Viard, R., Siebert, F., Chan, M. K., Hildebrandt, G., Dunst, J., Imhoff, D., Wurster, S., Wolff, R., Romanelli, P., Lartigau, E., Semrau, R., Soltys, S. G., Schweikard, A. 2016; 17 (3): 313-330

  Abstract

  Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

  View details for Web of Science ID 000377678100028

• Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group LANCET ONCOLOGY Thibault, I., Chang, E. L., Sheehan, J., Ahluwalia, M. S., Guckenberger, M., Sohn, M., Ryu, S., Foote, M., Lo, S. S., Muacevic, A., Soltys, S. G., Chao, S., Gerszten, P., Lis, E., Yu, E., Bilsky, M., Fisher, C., Schiff, D., Fehlings, M. G., Ma, L., Chang, S., Chow, E., Parelukar, W. R., Vogelbaum, M. A., Sahgal, A. 2015; 16 (16): E595-E603

  Abstract

  The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

  View details for PubMedID 26678212

• Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose-Escalation Trial Modlin, L. A., Choi, C. H., Gibbs, I. C., Wakelee, H. A., Neal, J., Pinder-Schenck, M. C., Chang, S. D., Adler, J. R., Harsh, G. R., Soltys, S. G. ELSEVIER SCIENCE INC. 2015: S178

  View details for DOI 10.1016/j.ijrobp.2015.07.425

  View details for Web of Science ID 000373215302104

• Stereotactic Radiosurgery for Facial Schwannomas D'Astous, M., Ho, A. L., Wallach, J., Choi, C. H., Soltys, S. G., Gibbs, I. C., Adler, J. R., Romanelli, P., Chang, S. D. ELSEVIER SCIENCE INC. 2015: E72-E73

  View details for DOI 10.1016/j.ijrobp.2015.07.728

  View details for Web of Science ID 000373215300182

• International Consensus Contouring Guidelines for Postoperative Spine Stereotactic Body Radiation Therapy (SBRT) Redmond, K. J., Robertson, S. P., Lo, S. S., Soltys, S. G., Ryu, S., McNutt, T. R., Chao, S. T., Barani, I. J., Yamada, Y., Ghia, A. J., Chang, E. L., Sheehan, J. P., Sahgal, A. ELSEVIER SCIENCE INC. 2015: S56

  View details for DOI 10.1016/j.ijrobp.2015.07.134

  View details for Web of Science ID 000373215301795

• A Phase I/II Dose-Escalation Trial of 3-Fraction Stereotactic Radiosurgery (SRS) for Large Resection Cavities of Brain Metastases Soltys, S. G., Seiger, K., Modlin, L. A., Gibbs, I. C., Hara, W., Kidd, E. A., Hancock, S. L., Diehn, M., Chang, S. D., Adler, J. R., Harsh, G. R., Li, G., Choi, C. H. ELSEVIER SCIENCE INC. 2015: S38

  View details for DOI 10.1016/j.ijrobp.2015.07.093

  View details for Web of Science ID 000373215301755

• Analysis of Tolerance of the Visual Pathway to Single Fraction and Hypofractionated Stereotactic Radiosurgery Hiniker, S. M., Modlin, L. A., Binkley, M. S., Harris, J. P., Seiger, K., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2015: E116–E117

  View details for DOI 10.1016/j.ijrobp.2015.07.844

  View details for Web of Science ID 000373215300297

• Spinal Stereotactic Radiosurgery: Dosimetric Correlates of Tumor Control Kumar, K. A., Choi, C. H., White, E. C., Qian, Y., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2015: E118

  View details for DOI 10.1016/j.ijrobp.2015.07.848

  View details for Web of Science ID 000373215300301

• First In-Human Stereotactic Arrhythmia Radioablation (STAR) of Ventricular Tachycardia: Dynamic Tracking Delivery Analysis and Implications Fahimian, B. P., Loo, B. W., Soltys, S. G., Zei, P., Lo, A. T., Maguire, P. J., Gardner, E., Wang, L. ELSEVIER SCIENCE INC. 2015: E466–E467

  View details for DOI 10.1016/j.ijrobp.2015.07.1738

  View details for Web of Science ID 000373215301232

• Neurocognitive Preservation for Whole-Brain Radiation Therapy is Cost-Effective for Well Selected Patients Durkee, B. Y., Sanford, J., Oh, A., Slate, D., Turner, B., Pollom, E., Gibbs, I. C., Gondi, V., Soltys, S. G. ELSEVIER SCIENCE INC. 2015: S91

  View details for DOI 10.1016/j.ijrobp.2015.07.219

  View details for Web of Science ID 000373215301878

• Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Shultz, D. B., Modlin, L. A., Jayachandran, P., von Eyben, R., Gibbs, I. C., Choi, C. Y., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Hancock, S. L., Soltys, S. G. 2015; 92 (5): 993-999

  Abstract

  To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS).We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS.Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites.Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  View details for DOI 10.1016/j.ijrobp.2015.04.036

  View details for Web of Science ID 000357900600018

  View details for PubMedID 26194677

• Is Less, More? The Evolving Role of Radiation Therapy for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Kirkpatrick, J. P., Laack, N. N., Kavanagh, B. D., Breneman, J. C., Shih, H. A. 2015; 92 (5): 963-966

  View details for DOI 10.1016/j.ijrobp.2015.03.003

  View details for Web of Science ID 000357900600012

  View details for PubMedID 26194672

• Stereotactic ablative radiotherapy for the treatment of refractory cardiac ventricular arrhythmia. Circulation. Arrhythmia and electrophysiology Loo, B. W., Soltys, S. G., Wang, L., Lo, A., Fahimian, B. P., Iagaru, A., Norton, L., Shan, X., Gardner, E., Fogarty, T., Maguire, P., Al-Ahmad, A., Zei, P. 2015; 8 (3): 748-750

  View details for DOI 10.1161/CIRCEP.115.002765

  View details for PubMedID 26082532

• COMPLETE RESPONSE TO VEMURAFINIB IN A PATIENT WITH METASTATIC ANAPLASTIC XANTHROASTROCYTOMA Thomas, R., Ajlan, A., Ziskin, J., Soltys, S., Reddy, S., Recht, L., Nagpal, S. OXFORD UNIV PRESS INC. 2014

  View details for DOI 10.1093/neuonc/nou265.32

  View details for Web of Science ID 000350452200661

• Repeat Stereotactic Radiosurgery (SRS) for Brain Metastases Locally Recurrent Following Initial SRS Jayachandran, P., Shultz, D., Modlin, L., Von Eyben, R., Gibbs, I. C., Chang, S., Harsh, G., Li, G., Adler, J., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2014: S320

  View details for DOI 10.1016/j.ijrobp.2014.05.1063

  View details for Web of Science ID 000342331401164

• Relative Monocytopenia, a Proposed Correlate of Decreased Vasculogenesis, Is Associated With Improved Survival in Patients With Glioblastoma Multiforme Osmundson, E., von Eyben, R., Nagpal, S., Recht, L., Brown, M., Soltys, S. G. ELSEVIER SCIENCE INC. 2014: S295-S296

  View details for DOI 10.1016/j.ijrobp.2014.05.995

  View details for Web of Science ID 000342331401101

• Repeat Stereotactic Radiosurgery (SRS) for New Brain Metastases Following Initial SRS: Accumulated Tumor Volume and Graded Prognostic Assessment (GPA) Score Calculated at Each Course Correlate With Overall Survival Shultz, D. B., Modlin, L. A., Jayachandran, P., Von Eiben, R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Adler, J. R., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2014: S311–S312

  View details for DOI 10.1016/j.ijrobp.2014.05.1039

  View details for Web of Science ID 000342331401141

• Repeat Resection Cavity Stereotactic Radiosurgery (SRS) for Brain Metastases Locally Recurrent Following Initial Resection Cavity Boost Modlin, L. A., Shultz, D. B., Jayachandran, P., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2014: S327

  View details for DOI 10.1016/j.ijrobp.2014.05.1081

  View details for Web of Science ID 000342331401182

• Monte Carlo Calculations for Radiosurgery of the Clivus Ho, A., Gibbs, I., Chang, S., Soltys, S. WILEY. 2014

  View details for DOI 10.1118/1.4888567

  View details for Web of Science ID 000436931100003

• Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Atalar, B., Modlin, L. A., Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Nagpal, S., Hanlon, A., Soltys, S. G. 2013; 87 (4): 713-718

  Abstract

  We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients.We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other).With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004).In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  View details for DOI 10.1016/j.ijrobp.2013.07.034

  View details for Web of Science ID 000325763300022

  View details for PubMedID 24054875

• Brain Metastases and Resection Cavities From Colorectal Carcinoma Treated With Stereotactic Radiosurgery Have Poor Local Control Compared to Noncolorectal Histology Pai, J., Wang, Z., Shaffer, J. L., Gibbs, I. C., Chang, D. T., Koong, A. C., Chang, S. D., Harsh, G. R., Li, G., Soltys, S. G. ELSEVIER SCIENCE INC. 2013: S161

  View details for DOI 10.1016/j.ijrobp.2013.06.415

  View details for Web of Science ID 000324503600398

• Evaluation of Tumor Expansion Following 3-Fraction Stereotactic Radiosurgery for Vestibular Schwannomas Shah, J. L., Shaffer, J. L., Gibbs, I. C., Chang, S. D., Harsh, G. R., Choi, C. Y., Hanlon, A., Soltys, S. G., Hanlon, A., Soltys, S. G. ELSEVIER SCIENCE INC. 2013: S263

  View details for DOI 10.1016/j.ijrobp.2013.06.685

  View details for Web of Science ID 000324503601072

• Cochlea radiation dose correlates with hearing loss after stereotactic radiosurgery of vestibular schwannoma. World neurosurgery Hayden Gephart, M. G., Hansasuta, A., Balise, R. R., Choi, C., Sakamoto, G. T., Venteicher, A. S., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Adler, J. R., Chang, S. D. 2013; 80 (3-4): 359-363

  Abstract

  OBJECTIVE: For multisession radiosurgery, no published data relate the volume and dose of cochlear irradiation to quantified risk of hearing loss. We conducted a retrospective, dosimetric study to evaluate the relationship between hearing loss after stereotactic radiosurgery (SRS) and the dose-volume of irradiated cochlea. METHODS: Cochlear dose data were retrospectively collected on consecutive patients who underwent SRS (18 Gy in 3 sessions) for vestibular schwanoma between 1999 and 2005 at Stanford University Hospital. Inclusion criteria included Gardner-Robertson (GR) grade I or II hearing prior to radiosurgical treatment, complete audiograms, and magnetic resonance imaging (MRI) follow-up. A cochlea dose-volume histogram was generated for each of the 94 patients who qualified for this study. RESULTS: GR grade I-II hearing posttreatment was maintained in 74% of patients (70/94). Median time to last follow-up audiogram was 2.4 years (range 0.4-8.9) and to last MRI was 3.6 years (range 0.5-9.4). Each higher level of cochlear irradiation was associated with increased risk of hearing loss. Larger cochlear volume was associated with lower risk of hearing loss. Controlling for differences in cochlear volume among subjects, each additional mm(3) of cochlea receiving 10 to 16 Gy (single session equivalent doses of 6.6-10.1 Gy3) significantly increased the odds of hearing loss by approximately 5%. CONCLUSIONS: Larger cochlear volume is associated with lower risk of hearing loss following trisession SRS for vestibular schwannoma. Controlling for this phenomenon, higher radiation dose and larger irradiated cochlear volume are significantly associated with higher risk of hearing loss. This study confirms and quantifies the risk of hearing loss following trisession SRS for vestibular schwannoma.

  View details for DOI 10.1016/j.wneu.2012.04.001

  View details for PubMedID 22484770

• CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas. Journal of neuro-oncology Jiang, B., Veeravagu, A., Feroze, A. H., Lee, M., Harsh, G. R., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2013; 114 (2): 209-218

  Abstract

  The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.

  View details for DOI 10.1007/s11060-013-1172-9

  View details for PubMedID 23748573

• Probabilities of Radiation Myelopathy Specific to Stereotactic Body Radiation Therapy to Guide Safe Practice INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sahgal, A., Weinberg, V., Ma, L., Chang, E., Chao, S., Muacevic, A., Gorgulho, A., Soltys, S., Gerszten, P. C., Ryu, S., Angelov, L., Gibbs, I., Wong, C. S., Larson, D. A. 2013; 85 (2): 341-347

  Abstract

  Dose-volume histogram (DVH) results for 9 cases of post spine stereotactic body radiation therapy (SBRT) radiation myelopathy (RM) are reported and compared with a cohort of 66 spine SBRT patients without RM.DVH data were centrally analyzed according to the thecal sac point maximum (Pmax) volume, 0.1- to 1-cc volumes in increments of 0.1 cc, and to the 2 cc volume. 2-Gy biologically equivalent doses (nBED) were calculated using an α/β = 2 Gy (units = Gy(2/2)). For the 2 cohorts, the nBED means and distributions were compared using the t test and Mann-Whitney test, respectively. Significance (P<.05) was defined as concordance of both tests at each specified volume. A logistic regression model was developed to estimate the probability of RM using the dose distribution for a given volume.Significant differences in both the means and distributions at the Pmax and up to the 0.8-cc volume were observed. Concordant significance was greatest for the Pmax volume. At the Pmax volume the fit of the logistic regression model, summarized by the area under the curve, was 0.87. A risk of RM of 5% or less was observed when limiting the thecal sac Pmax volume doses to 12.4 Gy in a single fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions.We report the first logistic regression model yielding estimates for the probability of human RM specific to SBRT.

  View details for DOI 10.1016/j.ijrobp.2012.05.007

  View details for Web of Science ID 000313642000020

  View details for PubMedID 22713832

• Cavity Volume Dynamics After Resection of Brain Metastases and Timing of Postresection Cavity Stereotactic Radiosurgery NEUROSURGERY Atalar, B., Choi, C. Y., Harsh, G. R., Chang, S. D., Gibbs, I. C., Adler, J. R., Soltys, S. G. 2013; 72 (2): 180-185

  Abstract

  An alternative treatment option to whole-brain irradiation after surgical resection of brain metastases is resection cavity stereotactic radiosurgery (SRS).To review the dynamics of cavity volume change after surgical resection with the goal of determining the optimal timing for cavity SRS.Preresection tumor, postresection/pre-SRS cavity, and post-SRS cavity volumes were measured for 68 cavities in 63 patients treated with surgery and postresection cavity SRS. Percent differences between volumes were calculated and correlation analyses were performed to assess volume changes before and after SRS.For the majority of tumors, the postresection cavity volume was smaller than the preresection tumor volume by a median percent volume change of -29% (range, -82% to 1258%), with larger preresection tumors resulting in greater cavity shrinkage (P < .001). To determine the optimal timing for cavity SRS, we examined cavity volume dynamics by comparing the early postresection (postoperative days 0-3) and treatment planning magnetic resonance imaging scans (median time to magnetic resonance imaging, 20 days; range, 9-33 days) and found no association between the postresection day number and volume change (P = .75). The volume decrease resulting from tumor resection was offset by the addition of a 2-mm clinical target volume margin, which is our current technique.The greatest volume change occurs immediately after surgery (postoperative days 0-3) with no statistically significant volume change occurring up to 33 days after surgery for most patients. Therefore, there is no benefit of cavity shrinkage in waiting longer than the first 1 to 2 weeks to perform cavity SRS.

  View details for DOI 10.1227/NEU.0b013e31827b99f3

  View details for Web of Science ID 000313734400028

  View details for PubMedID 23149969

• Impact of receptor status on prognosis among breast cancer patients with brain metastases treated with Cyberknife radiosurgery Fasola, C. E., Gibbs, I. C., Soltys, S. G., Horst, K. C. AMER ASSOC CANCER RESEARCH. 2012

  View details for DOI 10.1158/0008-5472.SABCS12-P4-16-11

  View details for Web of Science ID 000209704901068

• What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Atalar, B., Lieberson, R. E., Soltys, S. G. 2012; 84 (3): 688-693

  Abstract

  Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity.We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method.The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status (≥80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity.Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

  View details for DOI 10.1016/j.ijrobp.2012.01.028

  View details for Web of Science ID 000309560600051

  View details for PubMedID 22445007

• IGRT for Optic Nerve Sheath Meningioma Lo, A. T., Gibbs, I. C., Soltys, S. G., Wang, L. ELSEVIER SCIENCE INC. 2012: S763

  View details for DOI 10.1016/j.ijrobp.2012.07.2042

  View details for Web of Science ID 000310542902447

• Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Lieberson, R. E., Soltys, S. G. 2012; 84 (2): 336-342

  Abstract

  Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity.We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests.The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients.Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  View details for DOI 10.1016/j.ijrobp.2011.12.009

  View details for Web of Science ID 000308062700035

  View details for PubMedID 22652105

• Esophageal tolerance to high-dose stereotactic ablative radiotherapy DISEASES OF THE ESOPHAGUS Abelson, J. A., Murphy, J. D., Loo, B. W., Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q., Soltys, S. G., Gibbs, I. C. 2012; 25 (7): 623-629

  Abstract

  Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

  View details for DOI 10.1111/j.1442-2050.2011.01295.x

  View details for PubMedID 22168251

• Volumetric modulated arc therapy planning method for supine craniospinal irradiation JOURNAL OF RADIATION ONCOLOGY Chen, J., Chen, C., Atwood, T. F., Gibbs, I. C., Soltys, S. G., Fasola, C., Xing, L. 2012; 1 (3): 291–97

  View details for DOI 10.1007/s13566-012-0028-9

  View details for Web of Science ID 000218719700012

• CyberKnife stereotactic radiosurgery for the treatment of intramedullary spinal cord metastases JOURNAL OF CLINICAL NEUROSCIENCE Veeravagu, A., Lieberson, R. E., Mener, A., Chen, Y., Soltys, S. G., Gibbs, I. C., Adler, J. R., Tian, A. G., Chang, S. D. 2012; 19 (9): 1273-1277

  Abstract

  Spinal cord intramedullary metastases are uncommon and treatment options are limited. We reviewed our experience treating these lesions with radiosurgery to assess safety and efficacy, and to define preliminary treatment recommendations. With Institutional Review Board approval, we identified nine patients with 11 metastases treated with radiosurgery at Stanford University Hospital, between 2000 and 2010. We also reviewed all available published series discussing the treatment of spinal cord metastases. Our patients ranged in age from 33 years to 77 years (median 63 years) and included seven women and two men. Tumors ranged in size from 0.12 cm(3) to 6.4 cm(3) (median 0.48 cm(3)). Five were from breast cancer, two were non-small cell lung cancers, one was a cystic adenocarcinoma, and one was from an epithelioid hemangioepithelioma. All patients had neurologic deficits and multiple other metastases. We delivered 14 Gy to 27 Gy (median 21 Gy) in one to five (median 3) fractions. Complete follow-up was available for all nine patients. One patient remains alive 14 months after therapy. Of the eight deceased patients, survival ranged from one month and two days to nine months and six days (median four months and four days). There were no local recurrences or worsened neurological deficits. To our knowledge this is the largest reported series of spinal cord intramedullary metastases treated with radiosurgery. Survival was poor due to systemic disease, but radiosurgery appears to be safe and prevented local recurrences. With fewer sessions than conventional radiation and less morbidity than surgery, we feel radiosurgery is appropriate for the palliative treatment of these lesions.

  View details for DOI 10.1016/j.jocn.2012.02.002

  View details for Web of Science ID 000308730900014

  View details for PubMedID 22766103

• International Spine Radiosurgery Consortium Consensus Guidelines for Target Volume Definition in Spinal Stereotactic Radiosurgery INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Cox, B. W., Spratt, D. E., Lovelock, M., Bilsky, M. H., Lis, E., Ryu, S., Sheehan, J., Gerszten, P. C., Chang, E., Gibbs, I., Soltys, S., Sahgal, A., Deasy, J., Flickinger, J., Quader, M., Mindea, S., Yamada, Y. 2012; 83 (5): E597-E605

  Abstract

  Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery.Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines.Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic disease along the circumference of the epidural space.This report provides consensus guidelines for target volume definition for spinal metastases receiving upfront SRS in common clinical situations.

  View details for DOI 10.1016/j.ijrobp.2012.03.009

  View details for Web of Science ID 000306128100006

  View details for PubMedID 22608954

• Management of intracranial and extracranial chordomas with CyberKnife stereotactic radiosurgery JOURNAL OF CLINICAL NEUROSCIENCE Jiang, B., Veeravagu, A., Lee, M., Harsh, G. R., Lieberson, R. E., Bhatti, I., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2012; 19 (8): 1101-1106

  Abstract

  Chordomas are rare, malignant bone tumors of the axial skeleton, occurring particularly at the cranial base or in the sacro-coccygeal region. Although slow growing, chordomas are locally aggressive and challenging to treat. We evaluate the outcomes of skull base and spinal chordomas in 20 patients treated with CyberKnife (CK) stereotactic radiosurgery (SRS) (Accuray, Sunnyvale, CA, USA) between 1994 and 2010 at Stanford Hospital. There were 12 males and eight females (10-78 years; median age: 51.5 years). Eleven patients received CK as primary adjuvant therapy and nine patients received CK for multiple recurrences. The average tumor volume treated was 16.1cm(3) (2.4-45.9 cm(3)), with a mean marginal dose of 32.5 Gy (18-50 Gy). Median follow-up was 34 months (2-131 months). Overall, tumor control was achieved in 11 patients (55%), with eight patients showing tumor size reduction. However, nine patients showed progression and eventually succumbed to the disease (mean time from CK to death was 26.3 months). Of the patients treated with CK as the primary adjuvant therapy, 81.8% had stable or improved outcomes. Only 28.6% of those treated with CK for recurrences had stable or improved outcomes. The overall Kaplan-Meyer survival at five years from the first CK treatment was 52.5%. Moderate tumor control rates can be achieved with few complications with CK SRS. Poor control is associated with complex multiple surgical resections, long delay between initial resection and CK therapy, and recurrently aggressive disease uncontrolled by prior radiation.

  View details for DOI 10.1016/j.jocn.2012.01.005

  View details for Web of Science ID 000306500400009

  View details for PubMedID 22727205

• A Planned Neck Dissection Is Not Necessary in All Patients With N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Choi, C. Y., Fee, W. E., Pinto, H. A., Le, Q. 2012; 83 (3): 994-999

  Abstract

  To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease.We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed.The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04).In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.

  View details for DOI 10.1016/j.ijrobp.2011.07.042

  View details for Web of Science ID 000305256000055

  View details for PubMedID 22137026

• Stereotactic Radiosurgery as the Primary Treatment for New and Recurrent Paragangliomas: Is Open Surgical Resection Still the Treatment of Choice? WORLD NEUROSURGERY Lieberson, R. E., Adler, J. R., Soltys, S. G., Choi, C., Gibbs, I. C., Chang, S. D. 2012; 77 (5-6): 745-761

  Abstract

  Paragangliomas (PGs) or glomus tumors are rare, and publications comparing treatment alternatives are few. We sought to analyze our experience with stereotactic radiosurgery (SRS), review the literature, and develop treatment guidelines.We retrospectively examined the outcomes of 41 PGs in 36 patients treated with SRS at Stanford. Our data from medical records, telephone interviews, and imaging studies were combined with previously reported SRS data and compared to results following other treatments.With a median clinical follow-up of 4.8 years (3.9 years radiographic), local control was 100%. Complications included increase in preexistent vertigo in one patient and transient cranial neuropathies in two patients. Published surgical series describe a lower local control rate as well as more frequent and severe complications. Published radiation therapy (RT) series document a slightly lower local control rate than SRS, but SRS can be delivered more quickly and conveniently. Open surgery and other combinations of treatments appear to be required for several subpopulations of PG patients.We feel that SRS should be the primary treatment for most new and recurrent PGs. Even some very large PGs are appropriate for SRS. RT remains an appropriate option in some centers, especially those where SRS is not available. PGs occurring in the youngest patients, catecholamine secreting PGs, and PGs causing rapidly progressing neurologic deficits may be more appropriate for open resection. Metastatic PGs may benefit from combinations of chemotherapy and SRS or RT. Treatment guidelines are proposed.

  View details for DOI 10.1016/j.wneu.2011.03.026

  View details for Web of Science ID 000307523800038

  View details for PubMedID 22818172

• NORMAL TISSUE COMPLICATION PROBABILITY ESTIMATION BY THE LYMAN-KUTCHER-BURMAN METHOD DOES NOT ACCURATELY PREDICT SPINAL CORD TOLERANCE TO STEREOTACTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Luxton, G., Choi, C. Y., Gibbs, I. C., Chang, S. D., Adler, J. R., Soltys, S. G. 2012; 82 (5): 2025-2032

  Abstract

  To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear-quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS).From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18-30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8-30.9 Gy) and 22.0 Gy (range, 20.2-26.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD(50), and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n.In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy.The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP may not apply to the dosimetry of SRS. Further research with additional NTCP models is needed.

  View details for DOI 10.1016/j.ijrobp.2011.03.004

  View details for Web of Science ID 000301891300082

  View details for PubMedID 21531516

• Trigeminal neuralgia treatment dosimetry of the Cyberknife MEDICAL DOSIMETRY Ho, A., Lo, A. T., Dieterich, S., Soltys, S. G., Gibbs, I. C., Chang, S. G., Adler, J. R. 2012; 37 (1): 42-46

  Abstract

  There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patient's right, whereas the second is on the patient's left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculation algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.

  View details for DOI 10.1016/j.meddos.2010.12.012

  View details for Web of Science ID 000301035000009

  View details for PubMedID 21723113

• Impact of Dose Hot Spots on Spinal Cord Tolerance Following Stereotactic Body Radiotherapy: A Generalized Biological Effective Dose Analysis TECHNOLOGY IN CANCER RESEARCH & TREATMENT Sahgal, A., Ma, L., Fowler, J., Weinberg, V., Gibbs, I., Gerszten, P. C., Ryu, S., Soltys, S., Chang, E., Wong, C. S., Larson, D. A. 2012; 11 (1): 35-40

  Abstract

  The purpose of this study was to investigate the effects of high-dose inhomogeneous irradiation to small volumes of spinal cord with a new generalized biological effective dose (gBED) analysis for spine stereotactic body radiotherapy (SBRT). The gBED was applied to spinal cord dosimetric data (contoured per the thecal sac) at specified volumes for a cohort of five patients with radiation-induced myelopathy (RM) and compared to nineteen patients without RM post-SBRT. The spinal cord gBED was calculated and normalized to a conventional 2-Gy equivalent dose fraction scheme (α/β = 2 Gy for late toxicity). Differences between the conventional BED and those gBED calculations by accounting for small-volume dosing within the spinal cord was observed. Statistically significant differences in the mean gBED between the RM group and the non-RM group was observed both at the maximum point volume (gBED of 66 Gy vs. 37 Gy (p = 0.01), respectively) and at the 0.1 cm(3) volume (gBED of 53 Gy vs. 28 Gy (p = 0.01), respectively). No significant difference at the 0.1 cm(3) volume was observed based on the mean BED comparisons. No significant differences were observed at the larger 1 cm(3), 2 cm(3) or 5 cm(3) volumes for either BED or gBED comparisons. We conclude that differences in dose hot spots characteristics within small inhomogenously irradiated volumes of spinal cord can affect spinal cord tolerance following SBRT treatments.

  View details for Web of Science ID 000298867500005

  View details for PubMedID 22181329

• REIRRADIATION HUMAN SPINAL CORD TOLERANCE FOR STEREOTACTIC BODY RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sahgal, A., Ma, L., Weinberg, V., Gibbs, I. C., Chao, S., Chang, U., Werner-Wasik, M., Angelov, L., Chang, E. L., Sohn, M., Soltys, S. G., Letourneau, D., Ryu, S., Gerszten, P. C., Fowler, J., Wong, C. S., Larson, D. A. 2012; 82 (1): 107-116

  Abstract

  We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM).Spinal cord dose-volume histograms (DVHs) for 5 RM patients (5 spinal segments) and 14 no-RM patients (16 spine segments) were based on thecal sac contours at retreatment. Dose to a point within the thecal sac that receives the maximum dose (P(max)), and doses to 0.1-, 1.0-, and 2.0-cc volumes within the thecal sac were reviewed. The biologically effective doses (BED) using α/β = 2 Gy for late spinal cord toxicity were calculated and normalized to a 2-Gy equivalent dose (nBED = Gy(2/2)).The initial conventional radiotherapy nBED ranged from ~30 to 50 Gy(2/2) (median ~40 Gy(2/2)). The SBRT reirradiation thecal sac mean P(max) nBED in the no-RM group was 20.0 Gy(2/2) (95% confidence interval [CI], 10.8-29.2), which was significantly lower than the corresponding 67.4 Gy(2/2) (95% CI, 51.0-83.9) in the RM group. The mean total P(max) nBED in the no-RM group was 62.3 Gy(2/2) (95% CI, 50.3-74.3), which was significantly lower than the corresponding 105.8 Gy(2/2) (95% CI, 84.3-127.4) in the RM group. The fraction of the total P(max) nBED accounted for by the SBRT P(max) nBED for the RM patients ranged from 0.54 to 0.78 and that for the no-RM patients ranged from 0.04 to 0.53.SBRT given at least 5 months after conventional palliative radiotherapy with a reirradiation thecal sac P(max) nBED of 20-25 Gy(2/2) appears to be safe provided the total P(max) nBED does not exceed approximately 70 Gy(2/2), and the SBRT thecal sac P(max) nBED comprises no more than approximately 50% of the total nBED.

  View details for DOI 10.1016/j.ijrobp.2010.08.021

  View details for Web of Science ID 000298526100018

  View details for PubMedID 20951503

• Multisession Stereotactic Radiosurgery for Vestibular Schwannomas: Single-Institution Experience With 383 Cases NEUROSURGERY Hansasuta, A., Choi, C. Y., Gibbs, I. C., Soltys, S. G., Tse, V. C., Lieberson, R. E., Hayden, M. G., Sakamoto, G. T., Harsh, G. R., Adler, J. R., Chang, S. D. 2011; 69 (6): 1200-1209

  Abstract

  Single-session stereotactic radiosurgery (SRS) treatment of vestibular schwannomas results in excellent tumor control. It is not known whether functional outcomes can be improved by fractionating the treatment over multiple sessions.To examine tumor control and complication rates after multisession SRS.Three hundred eighty-three patients treated with SRS from 1999 to 2007 at Stanford University Medical Center were retrospectively reviewed. Ninety percent were treated with 18 Gy in 3 sessions, targeting a median tumor volume of 1.1 cm3 (range, 0.02-19.8 cm3).During a median follow-up duration of 3.6 years (range, 1-10 years), 10 tumors required additional treatment, resulting in 3- and 5-year Kaplan-Meier tumor control rates of 99% and 96%, respectively. Five-year tumor control rate was 98% for tumors < 3.4 cm3. Neurofibromatosis type 2-associated tumors were associated with worse tumor control (P = .02). Of the 200 evaluable patients with pre-SRS serviceable hearing (Gardner-Robertson grade 1 and 2), the crude rate of serviceable hearing preservation was 76%. Smaller tumor volume was associated with hearing preservation (P = .001). There was no case of post-SRS facial weakness. Eight patients (2%) developed trigeminal dysfunction, half of which was transient.Multisession SRS treatment of vestibular schwannomas results in an excellent rate of tumor control. The hearing, trigeminal nerve, and facial nerve function preservation rates reported here are promising.

  View details for DOI 10.1227/NEU.0b013e318222e451

  View details for Web of Science ID 000296794500024

  View details for PubMedID 21558974

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spinal Tumors NEUROSURGERY Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L., Gibbs, I. C. 2011; 69 (3): 533-539

  Abstract

  The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Although a growing body of evidence supports its role in the treatment of malignant spinal lesions, a much less extensive dataset exists for treatment of benign spinal tumors.To examine the safety and efficacy of stereotactic radiosurgery for treatment of benign, intradural extramedullary spinal tumors.From 1999 to 2008, 87 patients with 103 benign intradural extramedullary spinal tumors (32 meningiomas, 24 neurofibromas, and 47 schwannomas) were treated with stereotactic radiosurgery at Stanford University Medical Center. Forty-three males and 44 females had a median age of 53 years (range, 12-86). Twenty-five patients had neurofibromatosis. Treatment was delivered in 1 to 5 sessions (median, 2) with a mean prescription dose of 19.4 Gy (range, 14-30 Gy) to an average tumor volume of 5.24 cm (range, 0.049-54.52 cm).After a mean radiographic follow-up period of 33 months (range, 6-87), including 21 lesions followed for ≥ 48 months, 59% were stable, 40% decreased in size, and a single tumor (1%) increased in size. Clinically, 91%, 67%, and 86% of meningiomas, neurofibromas, and schwannomas, respectively, were symptomatically stable to improved at last follow-up. One patient with a meningioma developed a new, transient myelopathy at 9 months, although the tumor was smaller at last follow-up.As a viable alternative to microsurgical resection, stereotactic radiosurgery provides safe and efficacious long-term control of benign intradural, extramedullary spinal tumors with a low rate of complication.

  View details for DOI 10.1227/NEU.0b013e318218db23

  View details for Web of Science ID 000293586200003

  View details for PubMedID 21832967

• CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas JOURNAL OF HEMATOLOGY & ONCOLOGY Veeravagu, A., Jiang, B., Patil, C. G., Lee, M., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2011; 4

  Abstract

  Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas.In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively.Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%.CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.

  View details for DOI 10.1186/1756-8722-4-26

  View details for Web of Science ID 000291817100001

  View details for PubMedID 21645367

  View details for PubMedCentralID PMC3118387

• Stereotactic Radiosurgery of Cranial Nonvestibular Schwannomas: Results of Single- and Multisession Radiosurgery NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Sakamoto, G. T., Patel, D. A., Lieberson, R. E., Chang, S. D., Adler, J. R. 2011; 68 (5): 1200-1208

  Abstract

  Surgical resection of nonvestibular cranial schwannomas carries a considerable risk of postoperative complications. Stereotactic radiosurgery (SRS) offers a non-invasive treatment alternative. The efficacy and safety of multi-session SRS of nonvestibular cranial schwannomas has not been well studied.To analyze the results of single- and multi-session SRS of nonvestibular cranial schwannomas.From 2001 to 2007, 42 lesions in 40 patients were treated with SRS at Stanford University Medical Center, targeting schwannomas of cranial nerves IV (n = 1), V (n = 18), VII (n = 6), X (n = 5), XII (n = 2), jugular foramen (n = 8), and cavernous sinus (n = 2). SRS was delivered to a median marginal dose of 18 Gy (range, 15-33 Gy) in 1 to 3 sessions, targeting a median tumor volume of 3.2 cm (range, 0.1-23.7 cm). The median doses for treatments in 1 (n = 18), 2 (n = 9), and 3 (n = 15) sessions were 17.5, 20, and 18 Gy, respectively.With a median follow-up of 29 months (range, 6-84 months), tumor control was achieved in 41 of the 42 lesions. Eighteen of 42 lesions (43%) decreased in size; 23 tumors (55%) remained stable. There were 2 cases of new or worsening cranial nerve deficits in patients treated in single session; no patient treated with multi-session SRS experienced any cranial nerve toxicity (P = 0.18).SRS of nonvestibular cranial schwannomas provides excellent tumor control with minimal risk of complications. There was a trend towards decreased complications with multi-session SRS.

  View details for DOI 10.1227/NEU.0b013e31820c0474

  View details for Web of Science ID 000289230300033

  View details for PubMedID 21273918

• TOLERANCE OF THE SPINAL CORD TO STEREOTACTIC RADIOSURGERY: INSIGHTS FROM HEMANGIOBLASTOMAS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Choi, C. Y., Gibbs, I. C., Adler, J. R., Chang, S. D., Lieberson, R. E., Soltys, S. G. 2011; 80 (1): 213-220

  Abstract

  To evaluate spinal cord dose-volume effects, we present a retrospective review of stereotactic radiosurgery (SRS) treatments for spinal cord hemangioblastomas.From November 2001 to July 2008, 27 spinal hemangioblastomas were treated in 19 patients with SRS. Seventeen tumors received a single fraction with a median dose of 20 Gy (range, 18-30 Gy). Ten lesions were treated using 18-25 Gy in two to three sessions. Cord volumes receiving 8, 10, 12, 14, 16, 18, 20, 22, and 24 Gy and dose to 10, 100, 250, 500, 1000, and 2000 mm(3) of cord were determined. Multisession treatments were converted to single-fraction biologically effective dose (SFBED).Single-fraction median cord D(max) was 22.7 Gy (range, 17.8-30.9 Gy). Median V10 was 454 mm(3) (range, 226-3543 mm(3)). Median dose to 500 mm(3) cord was 9.5 Gy (range, 5.3-22.5 Gy). Fractionated median SFBED(3) cord D(max) was 14.1 Gy(3) (range, 12.3-19.4 Gy(3)). Potential toxicities included a Grade 2 unilateral foot drop 5 months after SRS and 2 cases of Grade 1 sensory deficits. The actuarial 3-year local tumor control estimate was 86%.Despite exceeding commonly cited spinal cord dose constraints, SRS for spinal hemangioblastomas is safe and effective. Consistent with animal experiments, these data support a partial-volume tolerance model for the human spinal cord. Because irradiated cord volumes were generally small, application of these data to other clinical scenarios should be made cautiously. Further prospective studies of spinal radiosurgery are needed.

  View details for DOI 10.1016/j.ijrobp.2010.01.040

  View details for Web of Science ID 000290006300031

  View details for PubMedID 21481724

• CyberKnife radiosurgery can control recurrent epidermoid cysts of the central nervous system. Journal of radiosurgery and SBRT Lieberson, R. E., Mener, A. n., Choi, C. n., Kalani, M. A., Soltys, S. G., Gibbs, I. C., Heit, G. n., Adler, J. R., Chang, S. D. 2011; 1 (3): 247–52

  Abstract

  Epidermoid cysts of the central nervous system may be difficult to resect and recurrent lesions may be impossible to control with open surgery. We identified three patients with recurrent epidermoids treated with radiosurgery at Stanford. One patient with a middle fossa lesion that had been resected twice in six years, presented with a 4.5 cubic centimeter recurrence and was treated with radiosurgery. Follow-up scans over three years showed no additional growth. Two patients had spinal lesions. One had undergone numerous, unsuccessful procedures in the three years before the radiosurgical treatment and subsequent open resection of a 3.8 cubic centimeter recurrence. His scans remain unremarkable eight years after treatment. The other, with acaudaequina mass, had required five open resections in 11 years. Following the last resection, the residual was treated radiosurgically. The lesion eventually increased in size, but became symptomatic only after seven years. A second course of radiosurgery was delivered. We believe that stereotactic radiosurgery can be safe for some epidermoid cysts of the central nervous system, decreases their growth rate, and may facilitate subsequent open surgery. It should be considered for select individuals with recurrent or unresectable lesions.

  View details for PubMedID 29296323

• Cyberknife Stereotactic Radiosurgery for Treatment of Atypical (Who Grade II) Cranial Meningiomas NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Jackson, P. S., Lieberson, R. E., Chang, S. D., Adler, J. R. 2010; 67 (5): 1180-1188

  Abstract

  The optimal management of subtotally resected atypical meningiomas is unknown.To perform a retrospective review of patients with residual or recurrent atypical meningiomas treated with stereotactic radiosurgery (SRS).Twenty-five patients were treated, either immediately after surgery (n = 15) or at the time of radiographic progression or treatment failure (n = 10). SRS was delivered to with a median marginal dose of 22 Gy (range, 16-30) in 1 to 4 fractions (median, 1), targeting a median tumor volume of 5.3 cm³ (range, 0.3-26.0).With a median follow-up time of 28 months (range, 3-67), the 12-, 24-, and 36-month actuarial local and regional control rates for all patients were 94%, 94%, 74%, and 90%, 90%, 62%, respectively. There were 2 cases of radiation toxicity. On univariate analysis, the number of recurrences before SRS (P = .046), late SRS (ie, waiting until tumor progression to initiate treatment) (P = .03), and age at treatment ≥ 60 years (P = .01) were significant predictors of recurrence. Of the 20 radiation-naïve patients, 2 patients failed with the targeted lesion and 3 elsewhere in the resection bed, resulting in 12-, 24- and 36-month actuarial local and regional control rates of 100%, 100%, 73% and 93%, 93%, 75%, respectively. The overall locoregional control rates at 12, 24, and 36 months were 93%, 93%, and 54%, respectively.Irradiation of the entire postoperative tumor bed may not be necessary for the majority of patients with subtotally resected atypical meningiomas. Patients in this series achieved outcomes comparable to that of historical control rates for larger volume, conventionally fractionated radiotherapy.

  View details for DOI 10.1227/NEU.0b013e3181f2f427

  View details for Web of Science ID 000283479500003

  View details for PubMedID 20871435

• STEREOTACTIC RADIOSURGERY FOR TREATMENT OF SPINAL METASTASES RECURRING IN CLOSE PROXIMITY TO PREVIOUSLY IRRADIATED SPINAL CORD INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Jackson, P. S., Minn, A. Y., Lieberson, R. E., Soltys, S. G. 2010; 78 (2): 499-506

  Abstract

  As the spinal cord tolerance often precludes reirradiation with conventional techniques, local recurrence within a previously irradiated field presents a treatment challenge.We retrospectively reviewed 51 lesions in 42 patients treated from 2002 to 2008 whose spinal metastases recurred in a previous radiation field (median previous spinal cord dose of 40 Gy) and were subsequently treated with stereotactic radiosurgery (SRS).SRS was delivered to a median marginal dose of 20 Gy (range, 10-30 Gy) in 1-5 fractions (median, 2), targeting a median tumor volume of 10.3 cm(3) (range, 0.2-128.6 cm(3)). Converting the SRS regimens with the linear quadratic model (α/β = 3), the median spinal cord maximum single-session equivalent dose (SSED) was 12.1 Gy(3) (range, 4.7-19.3 Gy(3)). With a median follow-up of 7 months (range, 2-47 months), the Kaplan-Meier local control and overall survival rates at 6/12 months were 87%/73% and 81%/68%, respectively. A time to retreatment of ≤12 months and the combination of time to retreatment of ≤12 months with an SSED of <15 Gy(10) were significant predictors of local failure on univariate and multivariate analyses. In patients with a retreatment interval of <12 months, 6/12 month local control rates were 88%/58%, with a SSED of >15 Gy(10), compared to 45%/0% with <15 Gy(10), respectively. One patient (2%) experienced Grade 4 neurotoxicity.SRS is safe and effective in the treatment of spinal metastases recurring in previously irradiated fields. Tumor recurrence within 12 months may correlate with biologic aggressiveness and require higher SRS doses (SSED >15 Gy(10)). Further research is needed to define the partial volume retreatment tolerance of the spinal cord and the optimal target dose.

  View details for DOI 10.1016/j.ijrobp.2009.07.1727

  View details for Web of Science ID 000282147000028

  View details for PubMedID 20133079

• SPINAL CORD TOLERANCE FOR STEREOTACTIC BODY RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sahgal, A., Ma, L., Gibbs, I., Gerszten, P. C., Ryu, S., Soltys, S., Weinberg, V., Wong, S., Chang, E., Fowler, J., Larson, D. A. 2010; 77 (2): 548-553

  Abstract

  Dosimetric data are reported for five cases of radiation-induced myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis per the biologically effective dose (BED) model was performed.Five patients with radiation myelopathy were compared to a subset of 19 patients with no radiation myelopathy post-SBRT. In all patients, the thecal sac was contoured to represent the spinal cord, and doses to the maximum point, 0.1-, 1-, 2-, and 5-cc volumes, were analyzed. The mean normalized 2-Gy-equivalent BEDs (nBEDs), calculated using an alpha/beta value of 2 for late toxicity with units Gy 2/2, were compared using the t test and analysis of variance test.Radiation myelopathy was observed at the maximum point with doses of 25.6 Gy in two fractions, 30.9 Gy in three fractions, and 14.8, 13.1, and 10.6 Gy in one fraction. Overall, there was a significant interaction between patient subsets and volume based on the nBED (p = 0.0003). Given individual volumes, a significant difference was observed for the mean maximum point nBED (p = 0.01).The maximum point dose should be respected for spine SBRT. For single-fraction SBRT 10 Gy to a maximum point is safe, and up to five fractions an nBED of 30 to 35 Gy 2/2 to the thecal sac also poses a low risk of radiation myelopathy.

  View details for DOI 10.1016/j.ijrobp.2009.05.023

  View details for Web of Science ID 000278167500033

  View details for PubMedID 19765914

• Esophageal Dose Tolerance in Stereotactic Body Radiotherapy Abelson, J. A., Murphy, J., Chang, S. D., Soltys, S. G., Le, Q., Loo, B. W., Gibbs, I. C. ELSEVIER SCIENCE INC. 2010: S267

  View details for DOI 10.1016/j.ijrobp.2010.07.636

  View details for Web of Science ID 000288775700576

• MULTISESSION CYBERKNIFE STEREOTACTIC RADIOSURGERY OF LARGE, BENIGN CRANIAL BASE TUMORS: PRELIMINARY STUDY NEUROSURGERY Tuniz, F., Soltys, S. G., Choi, C. Y., Chang, S. D., Gibbs, I. C., Fischbein, N. J., Adler, J. R. 2009; 65 (5): 898-907

  Abstract

  Although radiosurgery plays an important role in managing benign cranial base lesions, the potential for increased toxicity with single-session treatment of large tumors is a concern. In this retrospective study, we report the intermediate-term rate of local control, morbidity, and clinical outcomes of patients with large cranial base tumors treated with multisession stereotactic radiosurgery with the CyberKnife (Accuray, Inc., Sunnyvale, CA).Between 1999 and 2008, 34 consecutive patients with large (>15 cm), benign cranial base tumors (21 meningiomas, 9 schwannomas, 4 glomus jugulare tumors) underwent primary or postoperative radiosurgical treatment using a multisession approach at Stanford University and were considered in this retrospective study. Forty-four percent of these patients had undergone previous subtotal surgical resection or radiotherapy. CyberKnife radiosurgery was delivered in 2 to 5 sessions (median, 3 sessions) to a median tumor volume of 19.3 cm (range, 15.8-69.3 cm). The median marginal dose was 24 Gy (range, 18-25 Gy) prescribed to a median 78% isodose line.After a median clinical follow-up of 31 months (range, 12-77 months), 21% of patients experienced clinical improvement of neurological symptoms, whereas neurological status remained unchanged among the rest. Four patients experienced prolonged use of glucocorticoids owing to transient neurological worsening and radiographic signs of radiation injury. No permanent neurotoxicity was seen. To date, all tumors remain locally controlled.Over our modest length of follow-up, multisession radiosurgery appears to be a safe and effective option for selected large, benign brain and cranial base lesions.

  View details for DOI 10.1227/01.NEU.0000359316.34041.A8

  View details for Web of Science ID 000270876100013

  View details for PubMedID 19834402

• STEREOTACTIC RADIOSURGICAL TREATMENT OF CRANIAL AND SPINAL HEMANGIOBLASTOMAS NEUROSURGERY Moss, J. M., Choi, C. Y., Adler, J. R., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2009; 65 (1): 79-85

  Abstract

  Stereotactic radiosurgery has been used for nearly 2 decades to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. There is a paucity of long-term published radiosurgical treatment outcomes, particularly for spinal lesions, in a large patient population. The purpose of this study was to provide a long-term retrospective evaluation of radiosurgical hemangioblastoma treatment effectiveness, with a special emphasis on the relatively recent use of frameless, image-guided radiosurgery in the treatment of spinal lesions.From 1991 to 2007, 92 hemangioblastomas in 31 patients, 26 with von Hippel-Lindau disease, were treated with radiosurgery (27 tumors treated with frame-based linear accelerator radiosurgery, and 67 tumors were treated with CyberKnife radiosurgery). The mean patient age was 41 years (range, 18-81 years). The radiation dose to the tumor periphery averaged 23.4 Gy (range, 12-40 Gy). The mean tumor volume was 1.8 cm (range, 0.058-65.4 cm). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic, and magnetic resonance imaging scans.Clinical and radiographic follow-up data were available for 82 hemangioblastoma tumors. Only 13 (16%) of the treated hemangioblastomas progressed, whereas 18 tumors (22%) showed radiographic regression, and 51 tumors (62%) remained unchanged in size. With median follow-up of 69 months (range, 5-164 months), the actuarial local control rates at 36 and 60 months were 85% and 82%, respectively. Radiosurgery improved lesion-associated symptoms in 36 of 41 tumors. During the follow-up period, 9 patients died of causes unrelated to the progression of their treated hemangioblastomas, and 5 patients developed radiation necrosis.Stereotactic radiosurgery is safe and effective in the treatment of hemangioblastomas and is an attractive alternative to surgery for patients, including those with von Hippel-Lindau disease.

  View details for DOI 10.1227/01.NEU.0000348015.51685.D2

  View details for Web of Science ID 000268265600010

  View details for PubMedID 19574828

• CYBERKNIFE FOR BRAIN METASTASES OF MALIGNANT MELANOMA AND RENAL CELL CARCINOMA NEUROSURGERY Hara, W., Tran, P., Li, G., Su, Z., Puataweepong, P., Adler, J. R., Soltys, S. G., Chang, S. D., Gibbs, I. C. 2009; 64 (2): A26-A32

  Abstract

  To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma.We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified.The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%).CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.

  View details for DOI 10.1227/01.NEU.0000339118.55334.EA

  View details for Web of Science ID 000262797700009

  View details for PubMedID 19165071

• NONISOCENTRIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA NEUROSURGERY Adler, J. R., Bower, R., Gupta, G., Lim, M., Efron, A., Gibbs, I. C., Chang, S. D., Soltys, S. G. 2009; 64 (2): A84-A90

  Abstract

  Although stereotactic radiosurgery is an established procedure for treating trigeminal neuralgia (TN), the likelihood of a prompt and durable complete response is not assured. Moreover, the incidence of facial numbness remains a challenge. To address these limitations, a new, more anatomic radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongated segment of the retrogasserian cisternal portion of the trigeminal sensory root. Because the initial experience with this approach resulted in an unacceptably high incidence of facial numbness, a gradual dose and volume de-escalation was performed over several years. In this single-institution prospective study, we evaluated clinical outcomes in a group of TN patients who underwent lesioning with seemingly optimized nonisocentric radiosurgical parameters.Forty-six patients with intractable idiopathic TN were treated between January 2005 and June 2007. Eligible patients were either poor surgical candidates or had failed previous microvascular decompression or destructive procedures. During a single radiosurgical session, a 6-mm segment of the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy. Monthly neurosurgical follow-up was performed until the patient became pain-free. Longer-term follow-up was performed both in the clinic and over the telephone. Outcomes were graded as excellent (pain-free and off medication), good (>90% improvement while still on medication), fair (50-90% improvement), or poor (no change or worse). Facial numbness was assessed using the Barrow Neurological Institute Facial Numbness Scale score.Symptoms disappeared completely in 39 patients (85%) after a mean latency of 5.2 weeks. In most of these patients, pain relief began within the first week. TN recurred in a single patient after a pain-free interval of 7 months; all symptoms abated after a second radiosurgical procedure. Four additional patients underwent a repeat rhizotomy after failing to respond adequately to the first operation. After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients (72%), good in 11 patients (24%), and poor/no improvement in 2 patients (4%). Significant ipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) was reported in 7 patients (15%).Optimized nonisocentric CyberKnife parameters for TN treatment resulted in high rates of pain relief and a more acceptable incidence of facial numbness than reported previously. Longer follow-up periods will be required to establish whether or not the durability of symptom relief after lesioning an elongated segment of the trigeminal root is superior to isocentric radiosurgical rhizotomy.

  View details for DOI 10.1227/01.NEU.0000341631.49154.62

  View details for Web of Science ID 000262797700016

  View details for PubMedID 19165079

• Tolerance of the Spinal Cord to Stereotactic Radiosurgery: Insights from Hemangioblastomas Daly, M. E., Gibbs, I. C., Choi, C. E., Moss, J., Lieberson, R. E., Chang, S. D., Adler, J. R., Soltys, S. G. ELSEVIER SCIENCE INC. 2009: S101

  View details for DOI 10.1016/j.ijrobp.2009.07.246

  View details for Web of Science ID 000270573600215

• Stereotactic radiosurgery for a cardiac sarcoma: A case report TECHNOLOGY IN CANCER RESEARCH & TREATMENT Soltys, S. G., Kalani, M. Y., Cheshier, S. H., Szabo, K. A., Lo, A., Chang, S. D. 2008; 7 (5): 363-367

  Abstract

  Pulmonary artery intimal sarcoma is an uncommon tumor with a poor prognosis. We report a case of a 75-year-old man with a pulmonary artery sarcoma, recurrent following surgical resection. To palliate symptoms of this recurrence, he underwent CyberKnife stereotactic radiosurgery with a clinical and radiographic response of his treated disease. No acute or sub-acute toxicity was seen until the patient's death due to metastatic disease 10 weeks following treatment. The feasibility and short-term safety of this technique are reviewed, with emphasis on the stereotactic planning considerations, such as mediastinal organ movement and radiation tolerance.

  View details for Web of Science ID 000259799000003

  View details for PubMedID 18783285

• Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas NEUROSURGERY Patil, C. G., Hoang, S., Borchers, D. J., Sakamoto, G., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Chang, S. D., Adler, J. R. 2008; 63 (3): 435-440

  Abstract

  Anecdotal evidence suggests that radiosurgical ablation of parasagittal meningiomas may be associated with increased risk of subsequent edema. Potential predictors of postradiosurgical peritumoral edema, including parasagittal tumor location, tumor size, and treatment dose, were evaluated.We retrospectively reviewed records of 102 patients with 111 supratentorial meningiomas treated with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS). A median marginal dose of 18.0 Gy (range, 11.3-25.0 Gy) was delivered in 1 to 5 sessions (fractions). Potential predictors of posttreatment symptomatic edema were evaluated using Fisher's exact test.Of the 102 patients followed for a mean of 20.9 months (range, 6-77 mo), 15 (14.7%) developed symptomatic edema after SRS. Nine of 31 with parasagittal meningiomas (29.0%) and 6 of 80 with nonparasagittal supratentorial meningiomas (7.5%) developed symptomatic edema (P = 0.0053). Compared with patients with meningiomas in nonmidline supratentorial locations, patients with parasagittal meningiomas were more than 4 times as likely to develop symptomatic edema after SRS (odds ratio, 4.1; 95% confidence interval, 1.5-11.5). The 6-, 12-, and 18-month actuarial rates of symptomatic edema development were significantly greater for patients with parasagittal meningiomas than for patients with nonparasagittal meningiomas (17.8 versus 1.3%, 25.4 versus 5.8%, and 35.2 versus 7.8%, respectively).Patients with parasagittal meningiomas are at greater risk of developing peritumoral symptomatic edema after SRS. Close follow-up after SRS may be particularly important in such patients. These results highlight the need to pursue strategies that could decrease the incidence of postradiosurgical edema in patients with parasagittal meningioma.

  View details for Web of Science ID 000259625600010

  View details for PubMedID 18812954

• PRELIMINARY GUIDELINES FOR AVOIDANCE OF RADIATION-INDUCED MYELOPATHY FOLLOWING SPINE STEROTACTIC BODY RADIOSURGERY (SBRS) Sehgal, A., Gibbs, I., Ryu, S., Ma, L., Gerszten, P., Chang, U., Soltys, S., Weinberg, V., Fowler, J., Chang, E., Chao, S., Wong, S., Larson, D. ELSEVIER IRELAND LTD. 2008: S24

  View details for Web of Science ID 000433279300075

• Survival following CyberKnife radiosurgery and hypofractionated radiotherapy for newly diagnosed glioblastoma multiforme TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lipani, J. D., Jackson, P. S., Soltys, S. G., Sato, K., Adler, J. R. 2008; 7 (3): 249-255

  Abstract

  Current therapeutic goals for treatment of Glioblastoma Multiforme (GBM) involve gross total resection followed by multifractionated focal external beam radiation therapy (EBRT). Patients treated with optimal therapy have a median survival of approximately 12-15 months. In the present study, we sought to determine whether a hypofractionated dosing schedule using CyberKnife is at least as effective as multifractionated focal EBRT. A retrospective analysis was conducted on 20 histopathologically confirmed GBM patients treated with CyberKnife at Okayama Kyokuto Hospital in Japan after gross total resection (n=11), subtotal resection (n=8), or biopsy (n=1). Eight patients also received adjuvant ACNU and Vincrisitine chemotherapy according to local protocol; however, no patient received any other form of radiation besides post surgical/biopsy CyberKnife treatment. The treated tumor volumes ranged from 9.62 cm(3)-185.81 cm(3) (mean: 86.08 cm(3)). The marginal dose (D90) ranged from 19.99 Gy-41.47 Gy (mean: 34.58 Gy) with a maximum mean dose of 43.99 Gy (range: 23.33 Gy-56.89 Gy). The prescribed isodose line ranged from 50.38%-85.68% with a mean of 79.25%. Treatment was delivered in 1-8 fractions (mean: 5.65). Patients were followed from 2-36 months (mean: 16.45 months). Overall median survival was 16 months with 55% of patients alive at 12 months and 34% of patients alive at 24 months. Median survival of patients in Recursive Partitioning Analysis (RPA) classes III or IV was 32 months versus 12 months for those in RPA class V. Median survival for patients who received gross total resection was 36 months versus 8 months for those who underwent subtotal resection or biopsy. The results of this study using CyberKnife stereotactic radiosurgery (SRS) and hypofractionated radiotherapy compared favorably to historic data using focal EBRT in newly diagnosed post surgical GBM patients. A larger prospective analysis that compares CyberKnife SRS and hypofractionated radiotherapy to focal EBRT is warranted.

  View details for Web of Science ID 000256746700011

  View details for PubMedID 18473497

• Stereotactic radiosurgery of the postoperative resection cavity for brain metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Adler, J. R., Lipani, J. D., Jackson, P. S., Choi, C. Y., Puataweepong, P., White, S., Gibbs, I. C., Chang, S. D. 2008; 70 (1): 187-193

  Abstract

  The purpose of this study was to analyze results of adjuvant stereotactic radiosurgery (SRS) targeted at resection cavities of brain metastases without whole-brain irradiation (WBI).Patients who underwent SRS to the tumor bed, deferring WBI after resection of a brain metastasis, were retrospectively identified.Seventy-two patients with 76 cavities treated from 1998 to 2006 met inclusion criteria. The SRS was delivered to a median marginal dose of 18.6 Gy (range, 15-30 Gy) targeting an average tumor volume of 9.8 cm(3) (range, 0.1-66.8 cm(3)). With a median follow-up of 8.1 months (range, 0.1-80.5 months), 65 patients had follow-up imaging assessable for control analyses. Actuarial local control rates at 6 and 12 months were 88% and 79%, respectively. On univariate analysis, increasing values of conformality indices were the only treatment variables that correlated significantly with improved local control; local control was 100% for the least conformal quartile compared with 63% for the remaining quartiles. Target volume, dose, and number of sessions were not statistically significant.In this retrospective series, SRS administered to the resection cavity of brain metastases resulted in a 79% local control rate at 12 months. This value compares favorably with historic results with observation alone (54%) and postoperative WBI (80-90%). Given the improved local control seen with less conformal plans, we recommend inclusion of a 2-mm margin around the resection cavity when using this technique.

  View details for DOI 10.1016/j.ijrobp.2007.06.068

  View details for Web of Science ID 000251867700026

  View details for PubMedID 17881139

• Central Nervous System Metastases RADIATION ONCOLOGY: AN EVIDENCE-BASED APPROACH Gibbs, I. C., Soltys, S. G., Lu, J. J., Brady, L. W. 2008: 611-622

  View details for DOI 10.1007/978-3-540-77385-6_44

  View details for Web of Science ID 000267130300045

• CyberKnife (R) robotic radiosurgery system for tumor treatment EXPERT REVIEW OF ANTICANCER THERAPY Hara, W., Soltys, S. G., Gibbs, I. C. 2007; 7 (11): 1507-1515

  Abstract

  Defined by its high level of accuracy and rapid radiation dose fall-off, radiosurgery has emerged as an effective radiation technique over the past few decades. Although it was once limited to conditions of the brain, head and neck regions, technological advances in computing and imaging have allowed the application of radiosurgery to conditions throughout the entire body. Using advanced imaging and robotics, the CyberKnife (Accuray, Inc., Sunnyvale, CA, USA) is one of few systems capable of delivering radiosurgery with exquisite accuracy to tumors, cancers and other conditions throughout the body. This review focuses on the development, technology, clinical efficacy and future directions of the CyberKnife.

  View details for DOI 10.1586/14737140.7-11.1507

  View details for Web of Science ID 000251444300009

  View details for PubMedID 18020920

• Efficacy and safety of CyberKnife radiosurgery for acromegaly. Pituitary Roberts, B. K., Ouyang, D. L., Lad, S. P., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G., Gibbs, I. C., Remedios, L., Katznelson, L. 2007; 10 (1): 17

  View details for DOI 10.1007/s11102-007-0024-z

  View details for PubMedID 27519534

• Efficacy and safety of CyberKnife radiosurgery for acromegaly (doi.org/10.1007/s11102-007-0004-3) PITUITARY Roberts, B. K., Ouyang, D. L., Lad, S. P., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G., Gibbs, I. C., Remedios, L., Katznelson, L. 2007; 10 (1): 17-25

  Abstract

  Acromegaly is a disease characterized by GH hypersecretion, and is typically caused by a pituitary somatotroph adenoma. The primary mode of therapy is surgery, and radiotherapy is utilized as an adjuvant strategy to treat persistent disease. The aim of this study was to determine the efficacy and tolerability of CyberKnife stereotactic radiosurgery in acromegaly.A retrospective review of biochemical and imaging data for subjects with acromegaly treated with CyberKnife stereotactic radiosurgery between 1998 and 2005 at Stanford University Hospital.Nine patients with active acromegaly were treated with radiosurgery using the CyberKnife (CK).Biochemical response based on serum insulin-like growth factor-1 (IGF-1), anterior pituitary hormone function, and tumor size with MRI scans were analyzed.After a mean follow up of 25.4 months (range, 6-53 months), CK radiosurgery resulted in complete biochemical remission in 4 (44.4%) subjects, and in biochemical control with the concomitant use of a somatostatin analog in an additional subject. Smaller tumor size was predictive of treatment success: baseline tumor volume was 1.28 cc (+/- 0.81, SD) vs. 3.93 cc (+/- 1.54) in subjects with a normal IGF-1 vs. those with persistent, active disease, respectively (P = 0.02). The mean biologically effective dose (BED) was higher in subjects who achieved a normal IGF-1 vs. those with persistent, active disease, 172 Gy(3) (+/-28) vs. 94 Gy(3) (+/-17), respectively (P < 0.01). At least one new anterior pituitary hormone deficiency was observed after CK in 3 (33%) patients: two developed hypogonadism, and one developed panhypopituitarism.CK radiosurgery may be a valuable adjuvant therapy for the management of acromegaly.

  View details for DOI 10.1007/s11102-007-0024-z

  View details for Web of Science ID 000252215800002

• CyberKnife rhizotomy for facetogenic back pain: a pilot study. Neurosurgical focus Li, G., Patil, C., Adler, J. R., Lad, S. P., Soltys, S. G., Gibbs, I. C., Tupper, L., Boakye, M. 2007; 23 (6): E2-?

  Abstract

  By targeting the medial branches of the dorsal rami, radiofrequency ablation and facet joint injections can provide temporary amelioration of facet joint-producing (or facetogenic) back pain. The authors used CyberKnife radiosurgery to denervate affected facet joints with the goal of obtaining a less invasive yet more thorough and durable antinociceptive rhizotomy.Patients with refractory low-back pain, in whom symptoms are temporarily resolved by facet joint injections, were eligible. The patients were required to exhibit positron emission tomography-positive findings at the affected levels. Radiosurgical rhizotomy, targeting the facet joint, was performed in a single session with a marginal prescription dose of 40 Gy and a maximal dose of 60 Gy.Seven facet joints in 5 patients with presumptive facetogenic back pain underwent CyberKnife lesioning. The median follow-up was 9.8 months (range 3-16 months). The mean planning target volume was 1.7 cm(3) (range 0.9-2.7 cm(3)). A dose of 40 Gy was prescribed to a mean isodose line of 79% (range 75-80%). Within 1 month of radiosurgery, improvement in pain was observed in 3 of the 5 patients with durable responses at 16, 12, and 6 months, respectively, of follow-up. Two patients, after 12 and 3 months of follow-up, have neither improved nor worsened. No patient has experienced acute or late-onset toxicity.These preliminary results suggest that CyberKnife radiosurgery could be a safe, effective, and non-invasive alternative to radiofrequency ablation for managing facetogenic back pain. No patient suffered recurrent symptoms after radiosurgery. It is not yet known whether pain relief due to such lesions will be more durable than that produced by alternative procedures. A larger series of patients with long-term follow-up is ongoing.

  View details for PubMedID 18081475

• Radiosurgery for spinal cord arteriovenous malformations Soltys, S. G., Adler, J. R., Borchers, J. D., Chang, S. D., Gibbs, I. C. ELSEVIER SCIENCE INC. 2007: S104-S105

  View details for DOI 10.1016/j.ijrobp.2007.07.192

  View details for Web of Science ID 000249950200188

• Efficacy and safety of CyberKnife radiosurgery for acromegaly. Pituitary Roberts, B. K., Ouyang, D. L., Lad, S. P., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G., Gibbs, I. C., Remedios, L., Katznelson, L. 2007; 10 (1): 19-25

  Abstract

  Acromegaly is a disease characterized by GH hypersecretion, and is typically caused by a pituitary somatotroph adenoma. The primary mode of therapy is surgery, and radiotherapy is utilized as an adjuvant strategy to treat persistent disease. The aim of this study was to determine the efficacy and tolerability of CyberKnife stereotactic radiosurgery in acromegaly.A retrospective review of biochemical and imaging data for subjects with acromegaly treated with CyberKnife stereotactic radiosurgery between 1998 and 2005 at Stanford University Hospital.Nine patients with active acromegaly were treated with radiosurgery using the CyberKnife (CK).Biochemical response based on serum insulin-like growth factor-1 (IGF-1), anterior pituitary hormone function, and tumor size with MRI scans were analyzed.After a mean follow up of 25.4 months (range, 6-53 months), CK radiosurgery resulted in complete biochemical remission in 4 (44.4%) subjects, and in biochemical control with the concomitant use of a somatostatin analog in an additional subject. Smaller tumor size was predictive of treatment success: baseline tumor volume was 1.28 cc (+/- 0.81, SD) vs. 3.93 cc (+/- 1.54) in subjects with a normal IGF-1 vs. those with persistent, active disease, respectively (P = 0.02). The mean biologically effective dose (BED) was higher in subjects who achieved a normal IGF-1 vs. those with persistent, active disease, 172 Gy(3) (+/-28) vs. 94 Gy(3) (+/-17), respectively (P < 0.01). At least one new anterior pituitary hormone deficiency was observed after CK in 3 (33%) patients: two developed hypogonadism, and one developed panhypopituitarism.CK radiosurgery may be a valuable adjuvant therapy for the management of acromegaly.

  View details for PubMedID 17273921

• Image guided radiosurgery for spinal cord hemangioblastomas Soltys, S. G., Lipani, J. D., Adler, J. R., Chang, S. D., Gibbs, I. C. ELSEVIER SCIENCE INC. 2006: S247

  View details for DOI 10.1016/j.ijrobp.2006.07.471

  View details for Web of Science ID 000241221601014

• Sample classification from protein mass spectrometry, by 'peak probability contrasts' BIOINFORMATICS Tibshirani, R., Hastie, T., Narasimhan, B., Soltys, S., Shi, G. Y., Koong, A., Le, Q. T. 2004; 20 (17): 3034-3044

  Abstract

  Early cancer detection has always been a major research focus in solid tumor oncology. Early tumor detection can theoretically result in lower stage tumors, more treatable diseases and ultimately higher cure rates with less treatment-related morbidities. Protein mass spectrometry is a potentially powerful tool for early cancer detection. We propose a novel method for sample classification from protein mass spectrometry data. When applied to spectra from both diseased and healthy patients, the 'peak probability contrast' technique provides a list of all common peaks among the spectra, their statistical significance and their relative importance in discriminating between the two groups. We illustrate the method on matrix-assisted laser desorption and ionization mass spectrometry data from a study of ovarian cancers.Compared to other statistical approaches for class prediction, the peak probability contrast method performs as well or better than several methods that require the full spectra, rather than just labelled peaks. It is also much more interpretable biologically. The peak probability contrast method is a potentially useful tool for sample classification from protein mass spectrometry data.

  View details for DOI 10.1093/bioinformatics/bth357

  View details for Web of Science ID 000225361400017

  View details for PubMedID 15226172

• The use of plasma surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic patterns for detection of head and neck squamous cell cancers 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Soltys, S. G., Le, Q. T., Shi, G. Y., Tibshirani, R., Giaccia, A. J., Koong, A. C. AMER ASSOC CANCER RESEARCH. 2004: 4806–12

  Abstract

  Our study was undertaken to determine the utility of plasma proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry for the detection of head and neck squamous cell carcinomas (HNSCCs).Pretreatment plasma samples from HNSCC patients or controls without known neoplastic disease were analyzed on the Protein Biology System IIc SELDI-TOF mass spectrometer (Ciphergen Biosystems, Fremont, CA). Proteomic spectra of mass:charge ratio (m/z) were generated by the application of plasma to immobilized metal-affinity-capture (IMAC) ProteinChip arrays activated with copper. A total of 37356 data points were generated for each sample. A training set of spectra from 56 cancer patients and 52 controls were applied to the "Lasso" technique to identify protein profiles that can distinguish cancer from noncancer, and cross-validation was used to determine test errors in this training set. The discovery pattern was then used to classify a separate masked test set of 57 cancer and 52 controls. In total, we analyzed the proteomic spectra of 113 cancer patients and 104 controls.The Lasso approach identified 65 significant data points for the discrimination of normal from cancer profiles. The discriminatory pattern correctly identified 39 of 57 HNSCC patients and 40 of 52 noncancer controls in the masked test set. These results yielded a sensitivity of 68% and specificity of 73%. Subgroup analyses in the test set of four different demographic factors (age, gender, and cigarette and alcohol use) that can potentially confound the interpretation of the results suggest that this model tended to overpredict cancer in control smokers.Plasma proteomic profiling with SELDI-TOF mass spectrometry provides moderate sensitivity and specificity in discriminating HNSCC. Further improvement and validation of this approach is needed to determine its usefulness in screening for this disease.

  View details for Web of Science ID 000222840700027

  View details for PubMedID 15269156

• Is a planned neck dissection necessary after chemoradiotherapy in head and neck cancer patients with advanced nodal stage Soltys, S. G., Suen, A., Fee, W., Pinto, H., Sivanandan, R., Goode, R., Goffinet, D., Le, Q. ELSEVIER SCIENCE INC. 2004: S495

  View details for DOI 10.1016/S0360-3016(04)01732-8

  View details for Web of Science ID 000223854700608

• Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Sisk, E. A., Soltys, S. G., ZHU, S. B., Fisher, S. G., Carey, T. E., Bradford, C. R. 2002; 24 (9): 841-849

  Abstract

  Mutations of the p53 tumor-suppressor gene are common in squamous cell carcinoma of the head and neck (SCCHN) and may portend a worse prognosis. Human papillomavirus (HPV) represents another potential prognostic factor for SCCHN. The oncogenic potential of HPV may be due to the ability of its E6 oncoprotein to promote degradation of wild-type p53 protein. We wish to determine whether there is a lower incidence of p53 mutations in HPV-positive versus HPV-negative tumors, and if HPV and/or p53 status has an impact on survival.Thirty-two SCCHN specimens were analyzed for mutations of the p53 gene using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing. The HPV status of all specimens was evaluated by use of polymerase chain reaction with HPV consensus primers and Southern blot hybridization. Pertinent clinical information was obtained from chart review.Nonsilent p53 mutations were present in 2 of 15 (13%) of HPV-positive tumors compared with 6 of 17 (35%) of HPV-negative tumors (p =.229; Fisher's exact test, odds ratio.28). A survival advantage was found between HPV-positive compared with HPV-negative specimens (p =.0264) and between p53 wild type compared with p53 mutant specimens (p =.01) by univariate log rank analysis. When stratified according to both HPV and p53 status, a statistically significant survival difference was observed largely because of a 100% survival for the HPV-positive/p53 wild-type group (p =.003).This preliminary study supports the notion that the presence of HPV confers a survival advantage among HNSCC patients, particularly when p53 is wild type.

  View details for DOI 10.1002/hed.10146

  View details for Web of Science ID 000177651400003

  View details for PubMedID 12211048

• Facial Nerve Paralysis Occurring 4 Days following Stereotactic Radiosurgery for a Vestibular Schwannoma. Asian journal of neurosurgery Chow, K. K., Ajlan, A. n., Ho, A. L., Li, G. n., Soltys, S. G. ; 14 (1): 262–65

  Abstract

  Stereotactic radiosurgery (SRS) is commonly used for the treatment of vestibular schwannomas given its high rate of tumor control and low rate of complications. Facial nerve palsy has been reported several months after treatment as a rare late complication of SRS. Here, we report a case of facial weakness occurring only 4 days after treatment and discuss potential etiology and management considerations.

  View details for PubMedID 30937049

  View details for PubMedCentralID PMC6417297