John R. Adler, MD

All Publications

• Experimental and Monte Carlo based dosimetric investigation of a novel 3 mm radiosurgery 3 MV beam using the microSilicon detector. Journal of applied clinical medical physics Saße, K., Albers, K., Klassen, P. D., Marianyagam, N. J., Weidlich, G., Schneider, M. B., Chang, S., Adler, J., Poppe, B., Looe, H. K., Eulenstein, D. 2024: e14388

  Abstract

  The ZAP-X system is a novel gyroscopic radiosurgical system based on a 3 MV linear accelerator and collimator cones with a diameter between 4 and 25 mm. Advances in imaging modalities to detect small and early-stage pathologies allow for an early and less invasive treatment, where a smaller collimator matching the anatomical target could provide better sparing of surrounding healthy tissue.A novel 3 mm collimator cone for the ZAP-X was developed. This study aims to investigate the usability of a commercial diode detector (microSilicon) for the dosimetric characterization of this small collimator cone; and to investigate the underlying small field perturbation effects.Profile measurements in five depths as well as PDD and output ratio measurements were performed with a microSilicon detector and radiochromic EBT3 films. In addition, comprehensive Monte Carlo simulations were performed to validate the measurement observations and to quantify the perturbation effects of the microSilicon detector in these extremely small field conditions.It is shown that the microSilicon detector enables an accurate dosimetric characterization of the 3 mm beam. The profile parameters, such as the FWHM and 20%-80% penumbra width, agree within 0.1 to 0.2 mm between film and detector measurements. The output ratios agree within the measurement uncertainty between microSilicon detector and films, whereas the comparisons of the PDD results show good agreement with the Monte Carlo simulations. The analysis of the perturbation factors of the microSilicon detector reveals a small field correction factor of approximately 3% for the 3 mm circular beam and a correction factor smaller than 1.5% for field diameters above 3 mm.It could be shown that the microSilicon detector is well-suitable for the characterization of the new 3 mm circular beam of the ZAP-X system.

  View details for DOI 10.1002/acm2.14388

  View details for PubMedID 38762906

• Treatment of Refractory Bipolar Depression With Stereotactic Radiosurgery Targeting the Subgenual Cingulate Cortex CUREUS JOURNAL OF MEDICAL SCIENCE 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)

  View details for DOI 10.7759/cureus.57904

  View details for Web of Science ID 001209664200022

• 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

• Dosimetric Comparison of Dedicated Radiosurgery Platforms for the Treatment of Essential Tremor: Technical Report. Cureus Marianayagam, N. J., Paddick, I., Persad, A. R., Hori, Y. S., Maslowski, A., Thirunarayanan, I., Khanna, A. R., Park, D. J., Buch, V., Chang, S. D., Schneider, M. B., Yu, H., Weidlich, G. A., Adler, J. R. 2024; 16 (4): e57452

  Abstract

  Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing. Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being "reversible", deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by high-intensity focused ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a "second look". While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this brief technical report we compare the dosimetric profiles of three major radiosurgical platforms (Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS)) for the treatment of ET. In general, the GRS and Gamma Knife were shown to have the best theoretical dosimetric profiles for VIM lesioning. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

  View details for DOI 10.7759/cureus.57452

  View details for PubMedID 38699125

  View details for PubMedCentralID PMC11064878

• Commentary on "Navigation-Guided/Robot-Assisted Spinal Surgery: A Review Article". Neurospine Adler, J. R. 2024; 21 (1): 18-19

  View details for DOI 10.14245/ns.2448256.128

  View details for PubMedID 38569628

  View details for PubMedCentralID PMC10992666

• Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors ACTA NEUROCHIRURGICA Haider, G., Dadey, D. A., Rodrigues, A., Pollom, E. L., Adler, J. R., Veeravagu, A. 2023

  View details for DOI 10.1007/s00701-023-05826

  View details for Web of Science ID 001087777900004

• Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors. Acta neurochirurgica Haider, G., Dadey, D. Y., Rodrigues, A., Pollom, E. L., Adler, J. R., Veeravagu, A. 2023

  Abstract

  PURPOSE: Irradiating the surgical bed of resected brain metastases improves local and distant disease control. Over time, stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as the treatment standard of care because it minimizes long-term damage to neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access can result in sub-standard care for some patient populations. We aimed to analyze the clinical and socio-economic characteristics of patients who did not receive radiation after surgical resection of brain metastasis.METHODS: Our sample was obtained from Clinformatics Data Mart Database and included all patients from 2004 to 2021 who did or did not receive radiation treatment within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment.RESULTS: Of 8362 patients identified who had undergone craniotomy for resection of metastatic brain tumors, 3430 (41%) patients did not receive any radiation treatment. Compared to patients who did receive some form of radiation treatment (SRS or WBRT), patients who did not get any form of radiation were more likely to be older (p = 0.0189) and non-white (p = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (p < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (p < 0.01).CONCLUSION: Age, race, household income, and comorbidity status were associated with differential likelihood to receive post-operative radiation treatment.

  View details for DOI 10.1007/s00701-023-05826-w

  View details for PubMedID 37816918

• 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

• Impact of socio-economic factors on radiation treatment after resection of metastatic brain tumors: trends from a private insurance database. Journal of neuro-oncology Dadey, D. Y., Rodrigues, A., Haider, G., Pollom, E. L., Adler, J. R., Veeravagu, A. 2022

  Abstract

  BACKGROUND: Stereotactic radiosurgery (SRS) to the surgical bed of resected brain metastases is now considered the standard of care due to its advantages over whole brain radiation therapy (WBRT). Despite the upward trend in SRS adoption since the 2000s, disparities have been reported suggesting that socio-economic factors can influence SRS utilization.OBJECTIVE: To analyze recent trends in SRS use and identify factors that influence treatment.METHODS: We conducted a retrospective cohort study with the Optum Commercial Claims and Encounters Database and included all patients from 2004 to 2021 who received SRS or WBRT within 60days after resection of tumors metastatic to the brain.RESULTS: A total of 3495 patients met the inclusion and exclusion criteria. There were 1998 patients in the SRS group and 1497 patients in the WBRT group. SRS use now supersedes WBRT by a wide margin. Lung, breast and colon were the most common sites of primary tumor. Although we found no significant differences based on race among the treatment groups, patients with annual household income greater than $75,000 and those with some college or higher education are significantly more likely to receive SRS (OR 1.44 and 1.30; 95% CI 1.18-1.76 and 1.08-1.56; P=0.001 and 0.005, respective). Patients with Elixhauser Comorbidity Index of three or more were significantly more likely to receive SRS treatment.CONCLUSION: The use of post-surgical SRS for brain metastasis has increased significantly over time, however education and income were associated with differential SRS utilization.

  View details for DOI 10.1007/s11060-022-04031-6

  View details for PubMedID 35596873

• Non-ablative doses of focal ionizing radiation alters function of central neural circuits. Brain stimulation Zaer, H., Fan, W., Orlowski, D., Glud, A. N., Jensen, M. B., Worm, E. S., Lukacova, S., Mikkelsen, T. W., Fitting, L. M., Jacobsen, L. M., Portmann, T., Hsieh, J. Y., Noel, C., Weidlich, G., Chung, W., Riley, P., Jenkins, C., Adler, J. R., Schneider, M. B., Sørensen, J. C., Stroh, A. 2022

  Abstract

  Modulation of pathological neural circuit activity in the brain with a minimum of complications is an area of intense interest.The goal of the study was to alter neurons' physiological states without apparent damage of cellular integrity using stereotactic radiosurgery (SRS).We treated a 7.5 mm-diameter target on the visual cortex of Göttingen minipigs with doses of 40, 60, 80, and 100 Gy. Six months post-irradiation, the pigs were implanted with a 9 mm-wide, eight-shank multi-electrode probe, which spanned the radiation focus as well as the low-exposure neighboring areas.Doses of 40 Gy led to an increase of spontaneous firing rate, six months post-irradiation, while doses of 60 Gy and greater were associated with a decrease. Subjecting the animals to visual stimuli resulted in typical visual evoked potentials (VEP). At 40 Gy, a significant reduction of the P1 peak time, indicative of higher network excitability was observed. At 80 Gy, P1 peak time was not affected, while a minor reduction at 60 Gy was seen. No distance-dependent effects on spontaneous firing rate, or on VEP were observed. Post-mortem histology revealed no evidence of necrosis at doses below 60 Gy. In an in vitro assay comprising of iPS-derived human neuron-astrocyte co-cultures, we found a higher vulnerability of inhibitory neurons than excitatory neurons with respect to radiation, which might provide the cellular mechanism of the disinhibitory effect observed in vivo.We provide initial evidence for a rather circuit-wide, long-lasting disinhibitory effect of low sub-ablative doses of SRS.

  View details for DOI 10.1016/j.brs.2022.04.001

  View details for PubMedID 35395424

• Letter: The Path to Surgical Robotics in Neurosurgery. Operative neurosurgery (Hagerstown, Md.) Walcott, B. P., Spetzler, R. F., Chang, S. D., Muacevic, A., Moll, F., Adler, J. R. 2021

  View details for DOI 10.1093/ons/opab291

  View details for PubMedID 34409994

• Neuromodulation via Focal Radiation: Radiomodulation Update. Cureus Schneider, M. B., Walcott, B., Adler, J. R. 2021; 13 (4): e14700

  Abstract

  When radiation is focally delivered to brain tissue at sub-ablative doses, neural activity may be altered. When done at a specific brain circuit node or connection, this is referred to as "radiomodulation."Radiation-induced effects on brain tissue, basic science, and clinical research that supports the radiomodulation hypothesis are reviewed in this article. We review progress in defining the necessary parameters in terms of dose, volumes, and anatomical location.It may be possible to deliver therapeutic neuromodulation that is non-invasive, non-destructive, and durable.

  View details for DOI 10.7759/cureus.14700

  View details for PubMedID 33927960

• 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

• In Reply: The Zap-X Radiosurgical System in the Treatment of Intracranial Tumors: A Technical Case Report. Neurosurgery Adler, J. R., Weidlich, G. 2021

  View details for DOI 10.1093/neuros/nyab081

  View details for PubMedID 33733674

• Self-Shielding for the ZAP-X (R): Revised Characterization and Evaluation CUREUS Weidlich, G. A., Schneider, M., Simcic, V., Oostman, Z., Adler, J. R. 2021; 13 (3)

  View details for DOI 10.7759/cureus.13660

  View details for Web of Science ID 000625173800013

• Self-Shielding for the ZAP-X®: Revised Characterization and Evaluation. Cureus Weidlich, G. A., Schneider, M. B., Simcic, V., Oostman, Z., Adler, J. R. 2021; 13 (3): e13660

  Abstract

  The ZAP-X® is a newly designed, self-contained, and first-of-its-kind self-shielded therapeutic radiation therapy device dedicated to brain and head and neck stereotactic radiosurgery (SRS). By using an S-band linear accelerator (linac) and employing integrated minimal but sufficient shielding, the ZAP-X does not typically require a radiation bunker. At the same time, the self-shielded features of the ZAP-X are designed for more consistency of radiation protection, reducing the risk to radiation workers and others potentially exposed from a poorly designed or constructed radiotherapy vault. This study postulates that a radiosurgical system can be self-shielded, such that it produces radiation exposure levels deemed safe to the public while operating under a full clinical workload. The goal of self-shielding is achieved under all but the most exceptional clinical conditions. This work is intended to serve as guidance for the radiation safety evaluations of future ZAP-X treatment operations, following local or regional applicable regulatory requirements, and utilizing the unique provision of all or most of the required shielding material as an integral part of the device.

  View details for DOI 10.7759/cureus.13660

  View details for PubMedID 33824811

  View details for PubMedCentralID PMC8017256

• Lichenoid Keratosis Skin Biopsy: A Case Report of Malignant Hospital Charges CUREUS Adler, J. R., Do, H., Pfeffer, J. 2021; 13 (2): e13292

  Abstract

  Skin cancers are the most common malignancy and are especially common among light-skinned individuals in sun-exposed areas. While in many cases, a characteristic or classic appearance of the lesion is sufficient to make a definitive diagnosis, shave biopsy remains an important procedure when diagnosing many such raised lesions. Over the span of two months, a 66-year-old Caucasian male noted the appearance of a small, raised pruritic scaly lesion over his right upper chest. The differential diagnosis included both cancerous and benign lesions. During a 15-minute clinic visit, a simple shave biopsy was performed, and additionally, 10 small actinic keratoses on the patient's arms, legs, and back were treated with cryotherapy using liquid nitrogen. Later, a histologic examination of the biopsied lesion revealed a benign lichenoid keratosis. The patient was billed $10,187 for this outpatient experience.

  View details for DOI 10.7759/cureus.13292

  View details for Web of Science ID 000619512900020

  View details for PubMedID 33732557

  View details for PubMedCentralID PMC7956009

• Effects of Focal Ionizing Radiation of the Squid Stellate Ganglion on Synaptic and Axonal Transmission in the Giant-Fiber Pathway. Cureus Gilly, W. F., Teal, P., Graves, E. E., Lo, J., Schneider, M. B., Zasio, R., Adler, J. R. 2021; 13 (2): e13110

  Abstract

  Ionizing radiation is clinically used to treat neurological problems and reduce pathological levels of neural activity in the brain, but its cellular-level mechanisms are not well understood. Although spontaneous and stimulated synaptic activity has been produced in rodents by clinically and environmentally relevant doses of radiation, the effects on basic excitability properties of neurons have seldom been reported. This study examined the effects of focused ionizing radiation on synaptic transmission and action potential generation in the squid giant-fiber system, which includes the giant synapse between a secondary interneuron and the tertiary giant motor axons. Radiation of 140-300 Gy was delivered to a stellate ganglion of a living squid over several minutes, with the contralateral stellate ganglion serving as an internal control. No qualitative changes in the efficacy of synaptic transmission were noted in conjunction with stimulation of the input to the giant synapse, although in one irradiated ganglion, the refractory period increased from about 5 ms to more than 45 seconds. Small but significant changes in the action potential recorded from the giant motor axon in response to electrical stimulation were associated with an increased maximum rate of fall and a shortened action potential duration. Other action-potential parameters, including resting potential, overshoot, the maximum rate of the rise, and the refractory period were not significantly changed. Attempts to account for the observed changes in the action potential were carried through a Hodgkin-Huxley model of the action potential. This approach suggests that an increase in the maximum voltage-gated potassium conductance of about 50% mimics the action potential shortening and increased rate of fall that was experimentally observed. We propose that such an effect could result from phosphorylation of squid potassium channels.

  View details for DOI 10.7759/cureus.13110

  View details for PubMedID 33692914

  View details for PubMedCentralID PMC7938441

• Effects of Focal Ionizing Radiation of the Squid Stellate Ganglion on Synaptic and Axonal Transmission in the Giant-Fiber Pathway CUREUS Gilly, W. F., Teal, P., Graves, E. E., Lo, J., Schneider, M., Zasio, R., Adler, J. R. 2021; 13 (2)

  View details for DOI 10.7759/cureus.13110

  View details for Web of Science ID 000616643700021

• The Zap-X Radiosurgical System in the Treatment of Intracranial Tumors: A Technical Case Report. Neurosurgery Pan, L., Qu, B., Bai, J., Huang, L., Wang, J., Wang, C., Dai, X., Weidlich, G., Adler, J. R. 2021

  Abstract

  BACKGROUND AND IMPORTANCE: The Zap-X system (Zap Surgical Systems Inc, San Carlos, California) is a radically new surgical robot designed for brain and head and neck radiosurgery. It represents the first new dedicated brain stereotactic radiosurgery platform in almost half a century optimizing the goals of safety, speed, and accuracy. The Zap-X system was used in a required Chinese National Medical Products Administration clinical study. In early January 2020, 2 patients were treated with the Zap-X robot prior to a national COVID-19 lockdown. Both were closely followed via clinical exam and magnetic resonance imaging (MRI) imaging. Prospectively collected data were used to generate this report.CLINICAL PRESENTATION: Two female patients, each harboring either a trigeminal schwannoma or petroclival meningioma, were treated with the Zap-X robot. Respective tumor volumes were 2.60 and 4.02 cm3. A radiation dose of 13Gy was prescribed to the 50% isodose line. At 8 mo of follow-up, preoperative symptoms were either resolved or stable and MRI imaging demonstrated a 31% and 56% reduction in lesion volume, respectively. In both patients, symptoms improved, and tumor volumes decreased, whereas no major complication was observed.CONCLUSION: Given only 2 patients and short-term follow-up, any conclusions about the safety and efficacy of the Zap-X radiosurgery robot are preliminary. However, in the absence of any other published outcomes to date, this small case series may be of interest to many radiosurgical specialists.

  View details for DOI 10.1093/neuros/nyaa550

  View details for PubMedID 33442727

• An Intracortical Implantable Brain-Computer Interface for Telemetric Real-Time Recording and Manipulation of Neuronal Circuits for Closed-Loop Intervention. Frontiers in human neuroscience Zaer, H., Deshmukh, A., Orlowski, D., Fan, W., Prouvot, P., Glud, A. N., Jensen, M. B., Worm, E. S., Lukacova, S., Mikkelsen, T. W., Fitting, L. M., Adler, J. R., Schneider, M. B., Jensen, M. S., Fu, Q., Go, V., Morizio, J., Sorensen, J. C., Stroh, A. 2021; 15: 618626

  Abstract

  Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces (BCIs) should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Gottingen minipig model. The animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions.

  View details for DOI 10.3389/fnhum.2021.618626

  View details for PubMedID 33613212

• 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

• 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

• Vestibular Migraine Following Radiosurgery for Vestibular Schwannoma CUREUS Chae, R., McDermott, M., Muacevic, A., Adler, J. R., Sharon, J. D. 2020; 12 (6)

  View details for DOI 10.7759/cureus.8569

  View details for Web of Science ID 000539968700014

• Vestibular Migraine Following Radiosurgery for Vestibular Schwannoma. Cureus Chae, R., McDermott, M., Muacevic, A., Adler, J. R., Sharon, J. D. 2020; 12 (6): e8569

  Abstract

  Vestibular schwannoma (VS) is associated with dizziness and vertigo during all stages of treatment. This report describes a patient who presented with a one-year history of intermittent motion sickness, dizziness, headache, imbalance, and nausea. MRI showed a right-side VS in the cerebellopontine angle and internal auditory canal. The patient elected to undergo Gamma Knife radiosurgery for treatment. Within two to three months, she continued to experience recurring dizziness, vertigo, neck stiffness, and head pressure. She was referred for neurotology evaluation, which led to a diagnosis of vestibular migraine (VM). Her vestibular reflexes were intact. Subsequently, she was treated with diet modification and low-dose venlafaxine. She reported dramatically improved dizziness and vertigo symptoms at six-month follow-up. VM is a very common cause of dizziness that should always be included in the differential diagnosis, even in VS patients.

  View details for DOI 10.7759/cureus.8569

  View details for PubMedID 32670705

  View details for PubMedCentralID PMC7358935

• ZAP-X: A Novel Radiosurgical Device for the Treatment of Trigeminal Neuralgia. Cureus Romanelli, P., Chuang, C., Meola, A., Bodduluri, R. M., Adler, J. R. 2020; 12 (5): e8324

  Abstract

  Introduction The treatment of trigeminal neuralgia (TN) is one of the most demanding of all radiosurgery procedures, requiring accurate delivery and sharp dose fall off. ZAP-X®, a new, innovative frameless radiosurgical device, maybe an attractive platform for the treatment of TN and other functional brain disorders. Here, we compared the dosimetry of ZAP-X plans for a single patient to that generated by a well-established dedicated radiosurgery device, the CyberKnife. Methods Radiosurgery plans that delineated the cranial nerve from a single patient's fused computed tomography and magnetic resonance imaging (CT-MR) data set were planned on both the ZAP-X and CyberKnife, with the latter serving as a validated benchmark. The same target and treatment planning constraints were applied. Plans were evaluated by a physician with experience treating TN and a medical physicist. The ZAP-X treatment plan used two isocenters delivered through 4-mm collimators based on a non-isocentric plan that delivered 29,441 MU through 81 beams. The CyberKnife plans used a 5-mm collimator for a non-isocentric plan that delivered 17,880 MU through 88 beams. Results Based on visual inspection, the isodose volumes covered by ZAP-X and CyberKnife were similar at the prescription isodose (70% and 80%, respectively, with a maximum dose (Dmax) of 7500 cGy. The conformality index was better for the CyberKnife as compared to ZAP-X. However, the irradiated volumes were smaller at the 50%, 20%, and 10% isodoses for ZAP-X (0.12 cc, 0.57 cc, and 1.69 for ZAP-X; 0.18 cc, 0.91 cc, and 3.41 cc for CyberKnife). In particular, the 20% and 10% isodose volumes were much smaller for ZAP-X, especially on the axial and sagittal planes. Conclusions ZAP-X treatment planning for TN compares favorably with equivalent planning on CyberKnife. The brain volumes containing the 20% and 10% isodoses are smaller using ZAP-X, thus relatively sparing critical structures close to the target, including the Gasserian ganglion and brainstem. This feature could be of clinical relevance by potentially reducing treatment-related complications.

  View details for DOI 10.7759/cureus.8324

  View details for PubMedID 32617203

  View details for PubMedCentralID PMC7325335

• ZAP-X: A Novel Radiosurgical Device for the Treatment of Trigeminal Neuralgia CUREUS Romanelli, P., Chuang, C., Meola, A., Bodduluri, R. M., Adler, J. R. 2020; 12 (5)

  View details for DOI 10.7759/cureus.8324

  View details for Web of Science ID 000535877300003

• Clinical Considerations in Neurosurgical Radiosurgery in the Time of COVID-19. Cureus Pannullo, S. C., Chidambaram, S., Brandmaier, A., Knisely, J., Adler, J. R. 2020; 12 (4): e7671

  Abstract

  The COVID-19 pandemic is affecting all aspects of the healthcare ecosystem, including administration of stereotactic radiosurgery (SRS). The clinical and logistical challenges created by the COVID-19 public health crisis are clear, but the solutions to these issues are less readily apparent. The goal of this work is to use our experience at a large, academic medical center as a lens for interpreting the many looming issues specific to radiosurgery and its role in the treatment of brain and spine disorders. While the full impact of the pandemic remains to be seen, the aim of this paper is to provide a structural framework to optimize delivery of neurosurgically oriented radiosurgery with proposed clinical workflow strategies. Innovative solutions to the current pandemic crisis affecting the healthcare ecosystem will be driven by increased interdisciplinary and global dialogue.

  View details for DOI 10.7759/cureus.7671

  View details for PubMedID 32419998

  View details for PubMedCentralID PMC7226655

• Clinical Considerations in Neurosurgical Radiosurgery in the Time of COVID-19 CUREUS Pannullo, S. C., Chidambaram, S., Brandmaier, A., Knisely, J., Adler, J. 2020; 12 (4)

  View details for DOI 10.7759/cureus.7671

  View details for Web of Science ID 000525466100008

• Effects of Focal Radiation on [18 F]-Fluoro-D-Glucose Positron Emission Tomography in the Brains of Miniature Pigs: Preliminary Findings on Local Metabolism. Neuromodulation : journal of the International Neuromodulation Society Yeh, C., Cheng, M., Xiao, F., Chen, Y., Liu, C., Chen, H., Yen, R., Ju, Y., Chen, Y., Bodduluri, M., Yu, P., Chi, C., Chong, N. S., Wu, L., Adler, J. R., Schneider, M. B. 2020

  Abstract

  OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process.MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across ninemonths.RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60Gy or higher, with the effect persisting at ninemonths after radiosurgery. Only at 120Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation.CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.

  View details for DOI 10.1111/ner.13147

  View details for PubMedID 32270579

• A Novel Approach for Treatment of Uterine Fibroids: Stereotactic Radiosurgery as a Proposed Treatment Modality CURRENT OBSTETRICS AND GYNECOLOGY REPORTS Nezhat, C., Vang, N., Vu, M., Grossman, J., Skinner, J., Robinson, K., Saini, K., Vaid, A., Maule, L., Adler, J. R., Jang, J. W., Gibbs, I. C. 2020; 9 (1): 1–6

  View details for DOI 10.1007/s13669-020-00277-x

  View details for Web of Science ID 000525469300001

• Remote Robotic Spine Surgery. Neurospine Adler, J. R. 2020; 17 (1): 121–22

  View details for DOI 10.14245/ns.2040088.044

  View details for PubMedID 32252161

• Patents and Innovation Among Neurosurgeons from the American Association of Neurological Surgeons. Cureus Baron, R. B., Kessler, R. A., Bhammar, A., Boulis, N., Adler, J. R., Kohli, K., Hadjipanayis, C. 2020; 12 (2): e7031

  Abstract

  Objective Neurosurgeons have taken on the role of innovators, continuing to move the field forward over the centuries. More recently, innovation has taken the form of new technological devices and therapeutics, which require patenting. The aim of this study is to identify major areas of innovation in the field of neurosurgery by evaluating patent records. Methods This study quantifies the number of patents the American Association of Neurological Surgeons (AANS) neurosurgeons hold across different subspecialties. The United States Patent and Trademark Office (USPTO) patent database was queried using the names of 7,293 AANS members who filed patents between 1976 and 2019. Results A total of 346 (4.7%) AANS neurosurgeons hold a total of 1,025 patents. The number of patents held by each neurosurgeon ranged from one to 109. The areas that patents were filed under include cellular and genetic science (40), drug delivery (45), image guidance (82), neuromodulation (52), pain (7), peripheral nerve stimulation (24), spine (398), surgical devices (148), trauma (16), tumor (78), vascular (67), and other (68). No patents were filed under pediatrics (0). The fields with the greatest number of filed patents are spine, instruments/devices, and image guidance. Conclusion Given the technical nature of the field of neurosurgery, instruments and devices that improve localization, visualization, targeting, and spinal reconstruction are often in demand. Furthermore, since the rates of spinal procedures and implants continue to increase, higher patenting may be motivated by the opportunity to develop new products that can result in royalty payments to neurosurgeons. The advent of new technologies undoubtedly continues to push the field of neurosurgery forward.

  View details for DOI 10.7759/cureus.7031

  View details for PubMedID 32211264

  View details for PubMedCentralID PMC7082787

• Patents and Innovation Among Neurosurgeons from the American Association of Neurological Surgeons CUREUS Baron, R. B., Kessler, R. A., Bhammar, A., Boulis, N., Adler, J. R., Kohli, K., Hadjipanayis, C. 2020; 12 (2)

  View details for DOI 10.7759/cureus.7031

  View details for Web of Science ID 000514292500007

• 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

• A Perspective of International Collaboration Through Web-Based Telecommunication-Inspired by COVID-19 Crisis. Frontiers in human neuroscience Zaer, H., Fan, W., Orlowski, D., Glud, A. N., Andersen, A. S., Schneider, M. B., Adler, J. R., Stroh, A., Sorensen, J. C. 2020; 14: 577465

  Abstract

  The tsunami effect of the COVID-19 pandemic is affecting many aspects of scientific activities. Multidisciplinary experimental studies with international collaborators are hindered by the closing of the national borders, logistic issues due to lockdown, quarantine restrictions, and social distancing requirements. The full impact of this crisis on science is not clear yet, but the above-mentioned issues have most certainly restrained academic research activities. Sharing innovative solutions between researchers is in high demand in this situation. The aim of this paper is to share our successful practice of using web-based communication and remote control software for real-time long-distance control of brain stimulation. This solution may guide and encourage researchers to cope with restrictions and has the potential to help expanding international collaborations by lowering travel time and costs.

  View details for DOI 10.3389/fnhum.2020.577465

  View details for PubMedID 33328931

• Potential Clinical Significance of Overall Targeting Accuracy and Motion Management in the Treatment of Tumors That Move With Respiration: Lessons Learnt From a Quarter Century of Stereotactic Body Radiotherapy From Dose Response Models. Frontiers in oncology Mahadevan, A., Emami, B., Grimm, J., Kleinberg, L. R., Redmond, K. J., Welsh, J. S., Rostock, R., Kemmerer, E., Forster, K. M., Stanford, J., Shah, S., Asbell, S. O., LaCouture, T. A., Scofield, C., Butterwick, I., Xue, J., Muacevic, A., Adler, J. R. 2020; 10: 591430

  Abstract

  Objective: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking vs. compression or gating).Methods: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator.Results: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range.Conclusion: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.

  View details for DOI 10.3389/fonc.2020.591430

  View details for PubMedID 33634020

• Radionecrosis and cellular changes in small volume stereotactic brain radiosurgery in a porcine model. Scientific reports Zaer, H. n., Glud, A. N., Schneider, B. M., Lukacova, S. n., Vang Hansen, K. n., Adler, J. R., Høyer, M. n., Jensen, M. B., Hansen, R. n., Hoffmann, L. n., Worm, E. S., Sørensen, J. C., Orlowski, D. n. 2020; 10 (1): 16223

  Abstract

  Stereotactic radiosurgery (SRS) has proven an effective tool for the treatment of brain tumors, arteriovenous malformation, and functional conditions. However, radiation-induced therapeutic effect in viable cells in functional SRS is also suggested. Evaluation of the proposed modulatory effect of irradiation on neuronal activity without causing cellular death requires the knowledge of radiation dose tolerance at very small tissue volume. Therefore, we aimed to establish a porcine model to study the effects of ultra-high radiosurgical doses in small volumes of the brain. Five minipigs received focal stereotactic radiosurgery with single large doses of 40-100 Gy to 5-7.5 mm fields in the left primary motor cortex and the right subcortical white matter, and one animal remained as unirradiated control. The animals were followed-up with serial MRI, PET scans, and histology 6 months post-radiation. We observed a dose-dependent relation of the histological and MRI changes at 6 months post-radiation. The necrotic lesions were seen in the grey matter at 100 Gy and in white matter at 60 Gy. Furthermore, small volume radiosurgery at different dose levels induced vascular, as well as neuronal cell changes and glial cell remodeling.

  View details for DOI 10.1038/s41598-020-72876-w

  View details for PubMedID 33004849

  View details for PubMedCentralID PMC7529917

• 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

• Characterization of a Novel 3 Megavolt Linear Accelerator for Dedicated Intracranial Stereotactic Radiosurgery. Cureus Weidlich, G. A., Bodduluri, M., Achkire, Y., Lee, C., Adler, J. R. 2019; 11 (3): e4275

  Abstract

  The purpose of this article is to investigate and characterize from a physics perspective the Zap-X (ZAP Surgical Systems, Inc., San Carlos, CA), a new, dedicated self-contained and self-shielded radiosurgery system, focusing on beam energy and performance, leakage, radiation safety, dose delivery accuracy, regulations, quality assurance, and treatment planning. This investigation is required to establish the mechanical and overall performance specifications of the system and to establish baseline parameters for future clinical usage. The applied methods include measurements of energy, focal spot size, beam performance, dosimetry, beam data, treatment planning system, leakage radiation, acceptance testing, and commissioning. The results of the characterization reveal a 3 megavolt (MV) linear accelerator (linac) with a focal spot size of 2 mm, a dose rate of 1,500 MU/min at the isocenter with a dose linearity of 3%, a beam penumbra of less than 3 mm, and beam symmetry of less than 2%. Beam performance, as well as dosimetry characteristics, are suitable for intracranial radiosurgery. It can be concluded that the system was found to meet safety, accuracy, and performance requirements widely accepted in the radiation oncology and radiosurgery industry. Furthermore, the system was shown to meet the practical, clinical needs of the radiosurgery community.

  View details for DOI 10.7759/cureus.4275

  View details for PubMedID 31183264

  View details for PubMedCentralID PMC6538235

• Characterization of a Novel 3 Megavolt Linear Accelerator for Dedicated Intracranial Stereotactic Radiosurgery CUREUS Weidlich, G. A., Bodduluri, M., Achkire, Y., Lee, C., Adler, J. R. 2019; 11 (3)

  View details for DOI 10.7759/cureus.4275

  View details for Web of Science ID 000462083400009

• 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

• Milestones in stereotactic radiosurgery for the central nervous system. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Mitrasinovic, S., Zhang, M., Appelboom, G., Sussman, E., Moore, J. M., Hancock, S. L., Adler, J. R., Kondziolka, D., Steinberg, G. K., Chang, S. D. 2019; 59: 12–19

  Abstract

  INTRODUCTION: Since Lars Leksell developed the first stereotactic radiosurgery (SRS) device in 1951, there has been growth in the technologies available and clinical indications for SRS. This expansion has been reflected in the medical literature, which is built upon key articles and institutions that have significantly impacted SRS applications. Our aim was to identify these prominent works and provide an educational tool for training and further inquiry.METHOD: A list of search phrases relating to central nervous system applications of stereotactic radiosurgery was compiled. A topic search was performed using PubMed and Scopus databases. The journal, year of publication, authors, treatment technology, clinical subject, study design and level of evidence for each article were documented. Influence was proposed by citation count and rate.RESULTS: Our search identified a total of 10,211 articles with the top 10 publications overall on the study of SRS spanning 443-1313 total citations. Four articles reported on randomized controlled trials, all of which evaluated intracranial metastases. The most prominent subtopics included SRS for arteriovenous malformation, glioblastoma, and acoustic neuroma. Greatest representation by treatment modality included Gamma Knife, LINAC, and TomoTherapy.CONCLUSIONS: This systematic reporting of the influential literature on SRS for intracranial and spinal pathologies underscores the technology's rapid and wide reaching clinical applications. Moreover the findings provide an academic guide to future health practitioners and engineers in their study of SRS for neurosurgery.

  View details for PubMedID 30595165

• Milestones in stereotactic radiosurgery for the central nervous system JOURNAL OF CLINICAL NEUROSCIENCE Mitrasinovic, S., Zhang, M., Appelboom, G., Sussman, E., Moore, J. M., Hancock, S. L., Adler, J. R., Kondziolka, D., Steinberg, G. K., Chang, S. D. 2019; 59: 12–19

  View details for DOI 10.1016/j.jocn.2018.09.029

  View details for Web of Science ID 000457660200003

• Clinical efficacy of frameless stereotactic radiosurgery in the management of spinal metastases from thyroid carcinoma. Spine Hariri, O. n., Takayanagi, A. n., Lischalk, J. n., Desai, K. n., Florence, T. J., Yazdian, P. n., Chang, S. D., Vrionis, F. n., Adler, J. R., Quadri, S. A., Desai, A. n. 2019

  Abstract

  MINI: Study evaluates the efficacy of CyberKnife® (CK) SRS for thyroid spinal metastases (SM). Patients with SMs from thyroid carcinoma that were treated with CK SRS between 2003 and 2013were identified. CK can be safely used to treat SMs from thyroid cancer with a high rate of local control.A retrospective data review.To evaluate the efficacy of CyberKnife® SRS for thyroid SMs.Thyroid carcinoma is an infrequent cause of spinal metastasis (SM). The absolute efficacy of stereotactic radiosurgery (SRS) generally and CyberKnife® (CK) in particular remains poorly characterized for thyroid SM. The current study is the first to specifically evaluate the efficacy of CyberKnife® SRS for thyroid SMs.A retrospective review of patients at our institution between 2003 and 2013 was done. Details about tumor location, radiographic findings before and after CK SRS, tumor recurrence, prescription isodose level, total and maximum dose, number of fractions, and gross tumor volume coverage were similarly collected. For comparison with other studies, the biologically effective dose (BED) and the equivalent total dose in 2Gy fractions (EQD2) were calculated. Each patient was assessed for survival and local disease control from the time of the first CK session and survival analysis was carried out using the Kaplan-Meier method. Risk factors for local failure were assessed using multivariate logistic regression.A total of 12 patients with 32 spinal metastases from thyroid carcinoma that were treated with CK SRS were identified. Survival for 1, 2, and 3 years was 55%, 44%, and 33%, and local control was 67%, 56%, and 34% respectively. The study found that the single strongest factor associated with local control was prior radiotherapy (β-coefficient -27.72, p = 0.01). No complications occurred in the immediate or late follow-up period.This was the first study to specifically investigate the efficacy of CK for treatment of thyroid SMs. Our findings suggest that CK can be safely used to treat spinal SMs from thyroid cancer and is associated with a high rate of local control.4.

  View details for DOI 10.1097/BRS.0000000000003087

  View details for PubMedID 31261273

• #OpenAccess: Free online, open-access crowdsource-reviewed publishing is the future; traditional peer-reviewed journals are on the way out. CJEM Adler, J. R., Chan, T. M., Blain, J. B., Thoma, B., Atkinson, P. 2019; 21 (1): 11–14

  View details for PubMedID 30686272

• Correction: Characterization of a Novel Revolving Radiation Collimator. Cureus Weidlich, G. A., Schneider, M. B., Adler, J. R. 2019; 11 (5): c21

  Abstract

  [This corrects the article DOI: 10.7759/cureus.2146.].

  View details for DOI 10.7759/cureus.c21

  View details for PubMedID 31149411

  View details for PubMedCentralID PMC6527427

• Correction: Self-Shielding Analysis of the Zap-X System. Cureus Weidlich, G. A., Schneider, M. B., Adler, J. R. 2019; 11 (5): c22

  Abstract

  [This corrects the article DOI: 10.7759/cureus.1917.].

  View details for DOI 10.7759/cureus.c22

  View details for PubMedID 31149412

  View details for PubMedCentralID PMC6527428

• #OpenAccess: Free online, open-access crowdsource-reviewed publishing is the future; traditional peer-reviewed journals are on the way out CANADIAN JOURNAL OF EMERGENCY MEDICINE Adler, J. R., Chan, T. M., Blain, J., Thoma, B., Atkinson, P. 2019; 21 (1): 11–14

  View details for DOI 10.1017/cem.2018.481

  View details for Web of Science ID 000458526900005

• 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

• 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

• 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

• Characterization of a Novel Revolving Radiation Collimator CUREUS Weidlich, G. A., Schneider, M., Adler, J. R. 2018; 10 (2): e2146

  Abstract

  Introduction The ZAP-X is a novel self-contained and first-of-its-kind self-shielded therapeutic radiation device dedicated to brain and head and neck radiosurgery. By utilizing a 2.7-MV linear accelerator and incorporating a design in which a beam stop and major mechanical elements serve a radiation shielding function, the Zap-X does not typically require a radiation bunker. The unique collimator design of the Zap-X is especially critical to the performance of the overall system. The collimator consists of a shielded tungsten wheel oriented with its rotational axis perpendicular to the beam's central axis; the goal of this design is to minimize radiation leakage. Beam selection is accomplished by rotating the wheel within its tungsten-shielded housing. We investigated radiation leakage from the Zap-X collimator to determine its compliance with internationally accepted standards using direct radiation measurements. Materials and methods To measure collimator leakage in the plane of the patient, equidistant measurement stations were defined in a plane perpendicular to the central beam axis (cax) 1 m from this axis (1 m from the radiation focal spot). To measure leakage alongside and adjacent to the accelerator, equidistant measurement stations were located 1 m from the cax along a line parallel to the cax in the plane of the collimator wheel and along a line parallel to the cax 90 degrees offset from the first line of stations. Results Radiation leakage emanating from the collimating head of the linear accelerator in the patient plane ranged between 4.0 and 10.4 mR. Radiation along the linear accelerator (1000 R delivered in the primary beam) varied between 1.7 and 6.8 mR and constituted between 0.00017% to 0.00068% of the primary beam. The former radiation originated from X-ray target leakage, while the latter is produced directly by the linear accelerator and both contributed to the overall leakage radiation that would reach a patient. Discussion Due to the large diameter of the Zap-X tungsten collimator wheel and the massive Zap-X tungsten cylindrical collimator shield, the overall patient leakage is 0.00104% of the primary beam at a 1-m distance from the beam central axis in the patient plane. Leakage radiation in the patient plane is limited by the International Electrotechnical Commission (IEC) to 0.1% of the total primary radiation. Radiation leakage along the linear accelerator and the collimator housing was determined to be 0.00068% of primary radiation intensity. This leakage value is lower than the 0.1% leakage limit stipulated by IEC by more than a factor of 100. Conclusions Typically, an MV radiation therapy system minimizes exposure by utilizing a combination of device and structural shielding. However, the Zap-X has been uniquely designed to minimize the need for structural shielding. Our results indicate radiation leakage from the collimator meets internationally accepted standards as defined by the IEC.

  View details for PubMedID 29632755

• Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery Chin, A. L., Fujimoto, D. n., Kumar, K. A., Tupper, L. n., Mansour, S. n., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R. n., Li, G. n., Gephart, M. H., Ratliff, J. K., Tse, V. n., Usoz, M. n., Sachdev, S. n., Soltys, S. G. 2018

  Abstract

  Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data.To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors.We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy.Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with >5 yr and 24 courses with >10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed.Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

  View details for PubMedID 30445557

• Impact of CyberKnife Radiosurgery on Median Overall Survival of Various Parameters in Patients with 1-12 Brain Metastases. Cureus Murovic, J., Ding, V., Han, S. S., Adler, J. R., Chang, S. D. 2017; 9 (12): e1926

  Abstract

  Introduction This study's objective is to assessvarious patient, tumor and imaging characteristics andto compare median overall survival(OS)of 150 patients with 1-12 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray, Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014, treated with only CKRS for brain metastases were reviewed retrospectively for patient, tumor, and imaging characteristics. Parameters included demographics, Eastern Cooperative Oncology Group (ECOG) performance scores, number and control of extracranial disease (ECD) sites, cause of death (COD), histology, tumor volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging characteristics assessed were time of complete response (CR), partial response (PR), stable imaging or local failure (LF), and distal brain failure (DBF). The primary tumor Ki-67s of the breast carcinoma brain metastasis patients, who had the longest median OS of any group, were recorded when available. Results The predominant age group for the 150-patient cohort was the younger 17-65 years of age category, which was represented by 94 (62.7%). The 150-patient group had slightly more males, 79 (52.7%). The majority of 111 (74%) patients had an ECOG score of 1, 39 (26%) had 1 ECD site and uncontrolled ECD occurred in 112 (74.7%). The main COD was ECD in 106 (70.7%). The prevalent tumor histology was non-small cell lung carcinoma (88 of 150, 58.7%). The most common TV was 0-0.5 ccs (48 of 150, 32%). The majority of 125 (83.3%) patients did not undergo post-CKRS WBRT. Imaging outcomes were local control (LC) (CR, PR, or stable imaging) in 119 (79.3%), of whom 38 (25.3%) had CR, 56 (37.3%)PR and 25 (16.7%)stable imaging; LF was the outcome in 31 (20.7%) and DBF occured in 83 (55.3%). The median OS was 13 months. Patients17-65 years of age had a median OS of 13 months, while those 66-88 years, had 12 months. Females versus males had median OSof 15 versus 12 months. The most prolonged median OS of 21.5 months occurred in those with an ECOG score of 0. Patients with two ECD sites had a median OS of 14.5 months, while those with controlled ECD, 20.5 months. Patients with breast cancer brain metastases had the longest median OS of 23 months. The median OS for each of three (0-0.5 ccs, 0.6-1.5 ccs, 1.6-4.0 ccs) of four CKRS TV quartiles was 13 months and for those with 4.1-28.5 ccs, 10 months. Median OSfor patients with versus without post-CKRS WBRT was 23 versus 12 months. The longest median OS of 18.5 months for post-CKRS imaging outcomes was in patients with CR; those with LF had a median OS of 11.5 months. Of nine patients with breast carcinoma brain metastases with available Ki-67s from primary tumor resections, the Ki-67 values were ≥ 34% for four patients with CR, PR and stable imaging outcomes, and < 34% for five patients with LF. Conclusions An ECOG score of 0, ECD control, breast carcinoma brain metastasis histology. undergoing WBRT post-CKRS and CR imaging outcomes, each resulted in a longer median OS. The Ki-67 proliferation indices from primary breast carcinoma resection correlated well with the brain imaging outcomes in a small preliminary study in the present study's breast carcinoma patients with brain metastases.

  View details for PubMedID 29464135

• Self-Shielding Analysis of the Zap-X System. Cureus Weidlich, G. A., Schneider, M. B., Adler, J. R. 2017; 9 (12): e1917

  Abstract

  The Zap-X is a self-contained and first-of-its-kind self-shielded therapeutic radiation device dedicated to brain as well as head and neck stereotactic radiosurgery (SRS). By utilizing an S-band linear accelerator (linac) with a 2.7 megavolt (MV) accelerating potential and incorporating radiation-shielded mechanical structures, the Zap-X does not typically require a radiation bunker, thereby saving SRS facilities considerable cost. At the same time, the self-shielded features of the Zap-X are designed for more consistency of radiation protection, reducing the risk to radiation workers and others potentially exposed from a poorly designed or constructed radiotherapy vault. The hypothesis of the present study is that a radiosurgical system can be self-shielded such that it produces radiation exposure levels deemed safe to the public while operating under a full clinical workload. This study summarizes the Zap-X system shielding and found that the overall system radiation leakage values are reduced by a factor of 50 compared to the occupational radiation limit stipulated by the Nuclear Regulatory Commission (NRC) or agreement states. The goal of self-shielding is achieved under all but the most exceptional conditions for which additional room shielding or a larger restricted area in the vicinity of the Zap-X system would be required.

  View details for DOI 10.7759/cureus.1917

  View details for PubMedID 29441251

  View details for PubMedCentralID PMC5800761

• Impact of CyberKnife Radiosurgery on Median Overall Survival of Various Parameters in Patients with 1-12 Brain Metastases CUREUS Murovic, J., Ding, V., Han, S. S., Adler, J. R., Chang, S. D. 2017; 9 (12)

  View details for DOI 10.7759/cureus.1926

  View details for Web of Science ID 000453652000024

• Self-Shielding Analysis of the Zap-X System CUREUS Weidlich, G. A., Schneider, M., Adler, J. R. 2017; 9 (12)

  View details for DOI 10.7759/cureus.1917

  View details for Web of Science ID 000453652000016

• Radiosurgical Treatment Verification Using Removable Megavoltage Radiation Detectors CUREUS Jenkins, C. H., Kahn, R., Weidlich, G. A., Adler, J. R. 2017; 9 (11): e1889

  Abstract

  Introduction Accurate dose delivery is critical to the success of stereotactic radiosurgery. Unfortunately, verification of the accuracy of treatment delivery remains a challenging problem. Existing radiosurgery delivery paradigms are limited in their ability to verify the accurate delivery of radiation beams using data sampled from the beam after it has traversed the patient. The Zap-X Radiosurgery System (Zap Surgical Systems, San Carlos, CA) addresses this issue by implementing a fully integrated treatment delivery system that utilizes a factory commissioned megavoltage (MV) imager to measure the transmitted beam. The measured intensity is then compared with an expected value in order to confirm that treatment is proceeding as expected. The purpose of this study was to evaluate a prototype system and investigate the accuracy of an attenuation model used in generating the expected transmitted intensity values. Methods A prototype MV imager was used to measure transmitted beam intensities at various exposure levels and through several thicknesses of solid water. The data were used to evaluate imager linearity and model accuracy. Results Experimental results indicate that a quadratic attenuation model is appropriate for predicting beam attenuation and that the imager exhibits excellent dose linearity. Conclusions The MV imager system is shown to be capable of accurately acquiring the data needed to confirm treatment validity.

  View details for PubMedID 29392101

• Impact of CyberKnife Radiosurgery on Overall Survival and Various Parameters of Patients with 1-3 versus >= 4 Brain Metastases CUREUS Murovic, J., Ding, V., Han, S. S., Adler, J. R., Chang, S. D. 2017; 9 (10)

  View details for DOI 10.7759/cureus.1798

  View details for Web of Science ID 000453650800064

• Treatment Planning for Self-Shielded Radiosurgery. Cureus Adler, J. R., Schweikard, A., Achkire, Y., Blanck, O., Bodduluri, M., Ma, L., Zhang, H. 2017; 9 (9): e1663

  Abstract

  A five degreeof freedom, robotic,radiosurgical system dedicated to the brain is currently under development. In the proposed design, the machine is entirely self-shielded. The main advantage of a self-shielded system is the simplification of the system's installation, which can reduce the cost of radiosurgery. In this way, more patients can benefit from this minimally invasive and highly effective type of procedure. For technical reasons, space inside the shielded region is limited, which leads to constraints on the design. Here,two axes of rotation move a 3-megavolt linear accelerator around the patient's head at a source axis distance of 400 millimeters (mm), while the integrated patient table is characterized by two additional rotational, and one translational,degrees of freedom. Eight cone collimators of different diameters are available. The system can change the collimator automatically during treatment, using a collimator wheel. Since the linear accelerator can only move with two rotational axes, it is not possible to reposition the beam translationally (as it is in six degrees of freedom robotic radiosurgery). To achieve translational repositioning, it is necessary to move the patient couch. Thus, translational repositioning must be kept to a minimum during treatment. Our goal in this contribution is a preliminary investigation of dose distributions attainable with this type of design. Thus, we do not intend to design and evaluate the treatment planning system itself, but rather to establish that appropriate dose distributions can be achieved with this designunder realistic clinical circumstances. Our simulation suggests that dose gradients and conformity for complex target shapes, corresponding to state-of-the-art systems, can be achieved with this construction, althougha detailed evaluation of the system itself would be needed in the future.

  View details for PubMedID 29152420

• Treatment Planning for Self-Shielded Radiosurgery CUREUS Adler, J. R., Schweikard, A., Achkire, Y., Blanck, O., Bodduluri, M., Ma, L., Zhang, H. 2017; 9 (9)

  View details for DOI 10.7759/cureus.1663

  View details for Web of Science ID 000453625000029

• 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

• High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition. Cureus Dagne, B. A., Sunay, M. K., Cayla, N. S., Ouyang, Y., Knox, S. J., Giffard, R. G., Adler, J. R., Maciver, B. 2017; 9 (3)

  Abstract

  Studies on the effects of gamma radiation on brain tissue have produced markedly differing results, ranging from little effect to major pathology, following irradiation. The present study used control-matched animals to compare effects on a well characterized brain region following gamma irradiation. Male Sprague-Dawley rats were exposed to 60 Gy of whole brain gamma radiation and, after 24-hours, 48-hours, and one-week periods, hippocampal brain slices were isolated and measured for anatomical and physiological differences. There were no major changes observed in tissue appearance or evoked synaptic responses at any post-irradiation time point. However, exposure to 60 Gy of irradiation resulted in a small, but statistically significant (14% change; ANOVA p < 0.005; n = 9) reduction in synaptic inhibition seen at 100 ms, indicating a selective depression of the gamma-aminobutyric acid (GABAA) slow form of inhibition. Population spike (PS) amplitudes also transiently declined by ~ 10% (p < 0.005; n = 9) when comparing the 24-hour group to sham group. Effects on PS amplitude recovered to baseline 48 hour and one week later. There were no obvious negative pathological effects; however, a subtle depression in circuit level inhibition was observed and provides evidence for 'radiomodulation' of brain circuits.

  View details for DOI 10.7759/cureus.1076

  View details for PubMedID 28401026

• Embolization Followed by Radiosurgery for the Treatment of Brain Arteriovenous Malformations (AVMs) WORLD NEUROSURGERY Marks, M. P., Marcellus, M. L., Santarelli, J., Dodd, R. L., Do, H. M., Chang, S. D., Adler, J. R., Mlynash, M., Steinberg, G. K. 2017; 99: 471-476

  Abstract

  Embolization has been proposed to reduce the size of the arteriovenous malformation (AVM) nidus in advance of radiosurgical treatment. Embolization followed by radiosurgery for brain AVMs, however, is controversial.We assessed the impact of embolization on nidal size before radiosurgical treatment and evaluated cure rates and complications by using embolization followed by radiosurgery.A retrospective review of our institutional AVM database identified 91 patients treated from 1995 to 2009 with embolization followed by radiosurgery. Pre- and postembolization AVM volumes were measured with angiography, and the modified radiation-based AVM scores (RBAS) also were calculated pre- and postembolization. RBAS determined from pre-embolization volumes were correlated with postradiosurgical obliteration.Median AVM volume declined from 18.8 mL (interquartile range, 10.2-32.2 mL) to 9.9 mL (3.1-19.2 mL) after embolization, P < 0.00003. Median RBAS scores decreased from 2.6 mL (1.8-3.9 mL) to 1.8 mL (1.0-2.8 mL), P < 0.00003. Two of 91 (2.2%) had new fixed deficits after embolization; however, no patient had new disabling deficits (modified Rankin Scale score >2). A total of 71 of 91 (79%) have had >3 years' follow-up, and 40 (56%) had complete obliteration, with 38 (53%) having excellent outcomes (complete obliteration without neurologic decline). Excellent outcome was seen in 90% of patients with modified RBAS score <1, 66% of patients with score 1-1.5, 50% patients with score 1.5-2, and 43% of patients with score >2.These data suggest that embolization of brain AVMs can safely and effectively reduce the treatment volume before radiosurgery. Combined therapy with embolization and radiosurgery does not appear to adversely affect rates of excellent outcome.

  View details for DOI 10.1016/j.wneu.2016.12.059

  View details for Web of Science ID 000397190100066

• 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

• Alteration of Interneuron Immunoreactivity and Autophagic Activity in Rat Hippocampus after Single High-Dose Whole-Brain Irradiation. Cureus Ouyang, Y. B., Ning, S. n., Adler, J. R., Maciver, B. n., Knox, S. J., Giffard, R. n. 2017; 9 (6): e1414

  Abstract

  The effects of high dose gamma radiation on brain tissue are poorly understood, with both limited and major changes reported. The present study compared the effects of gamma irradiation on the expression of interneuron markers within the hippocampal cornu ammonis 1 (CA1) region with expression in control matched rats. This area was chosen for study because of its well-characterized circuitry. Male Sprague-Dawley rats were exposed to 60 Gy of whole brain gamma radiation and after 24 or 48 hours, the brains were removed, fixed and sectioned to quantitate expression of parvalbumin (PV), calbindin-D28K (CB), reelin, neuropeptide-Y (NPY), and somatostatin. All of these markers increased in expression over the first 48 hours, except NPY, which decreased. This provides novel information on changes in gene expression in the hippocampal interneurons following radiation. Staining for Beclin 1, a marker of autophagy, increased most strongly in the subgranular zone (SGZ) of the dentate gyrus (DG). Overall, the results are consistent with the hypothesis that increased intracellular calcium follows irradiation, leading to an increased expression of calcium binding proteins. Increased autophagy occurs in the neurogenic zone of the dentate hilus, consistent with reduced effective neurogenesis after irradiation.

  View details for PubMedID 28861331

  View details for PubMedCentralID PMC5576964

• 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

• High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition Cureus Dagne, B. A., Sunay, M. K., Cayla, N. S., Ouyang, Y., Knox, S. J., Giffard, R. G., Adler, J. D., MacIver, M. B. 2017: e1076

  Abstract

  Studies on the effects of gamma radiation on brain tissue have produced markedly differing results, ranging from little effect to major pathology, following irradiation. The present study used control-matched animals to compare effects on a well characterized brain region following gamma irradiation. Male Sprague-Dawley rats were exposed to 60 Gy of whole brain gamma radiation and, after 24-hours, 48-hours, and one-week periods, hippocampal brain slices were isolated and measured for anatomical and physiological differences. There were no major changes observed in tissue appearance or evoked synaptic responses at any post-irradiation time point. However, exposure to 60 Gy of irradiation resulted in a small, but statistically significant (14% change; ANOVA p < 0.005; n = 9) reduction in synaptic inhibition seen at 100 ms, indicating a selective depression of the gamma-aminobutyric acid (GABAA) slow form of inhibition. Population spike (PS) amplitudes also transiently declined by ~ 10% (p < 0.005; n = 9) when comparing the 24-hour group to sham group. Effects on PS amplitude recovered to baseline 48 hour and one week later. There were no obvious negative pathological effects; however, a subtle depression in circuit level inhibition was observed and provides evidence for 'radiomodulation' of brain circuits.

  View details for DOI 10.7759/cureus.1076

  View details for PubMedCentralID PMC5382012

• Impact of CyberKnife Radiosurgery on Overall Survival and Various Parameters of Patients with 1-3 versus ≥ 4 Brain Metastases. Cureus Murovic, J. n., Ding, V. n., Han, S. S., Adler, J. R., Chang, S. D. 2017; 9 (10): e1798

  Abstract

  Introduction This study's objective is to compare the overall survivals (OSs) and various parameters of patients with 1-3 versus ≥ 4 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray, Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014, treated with only CKRS for brain metastases were reviewed retrospectively for overall survival (OS) and patient, tumor, and imaging characteristics. Parameters included demographics, Eastern Cooperative Oncology Group (ECOG) performance scores, number and control of extracranial disease (ECD) sites, cause of death (COD), histology, tumor volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging characteristics assessed were time of complete response (CR), partial response (PR), stable imaging or local failure (LF), and distal brain failure (DBF). Patients and their data were divided into those with 1-3 (group 1) versus ≥ 4 brain metastases (group 2). For each CR and LF patient, absolute neutrophil count (ANC), absolute lymphocyte count (ALC)), and ANC/ALC ratio (NLR) were obtained, when available, at the time of CKRS. Results Both group 1 and group 2 had a median OS of 13 months. The patient median age for the 115 group 1 patients versus the 35 group 2 patients was 62 versus 56 years. Group 1 had slightly more males and group 2, females. The predominant ECOG score for each group was 1 and the number of ECD sites was one and two, respectively. Uncontrolled ECD occurred in the majority of both group 1 and group 2 patients. The main COD was ECD in both groups. The prevalent tumor histology for groups 1 and 2 was non-small cell lung carcinoma. Median TVs were 1.08 cc versus 1.42 cc for groups 1 and 2, respectively. The majority of patients in both groups did not undergo post-CKRS WBRT. Imaging outcomes were LC (CR, PR, or stable imaging) in 93 (80.9%) and 26 (74.3%) group 1 and 2 patients, of whom 32 (27.8%) and six (17.1%) had CR; 38 (33.0%) and 18 (51.4%), PR and 23 (20.0%) and two (5.7%), stable imaging; LF was the outcome in 22 (19.1%) and nine (25.7%) patients, and DBF occurred in 62 (53.9%) and 21 (60.0%), respectively. Uni- and multivariable analyses showed the independent parameters of a lower ECOG score, a greater number of ECD sites and uncontrolled ECD were significantly associated with greater mortality risk with and without accounting for other covariates. At CKRS, 19 group 1 and 2 CR patients had a mean ANC of 5.88 K/µL and a mean ALC of 1.31 K/µL and 13 (68%) of 19 had NLRs ≤ five, while 11 with LFs had a mean ANC of 5.22 K/µL and a mean ALC of 0.93 K/µL and seven (64%) had NLRs > five. An NLR ≤ five and high ALC was associated with a CR and an NLR > five and a low ALC with an LF. Conclusions Median OS post-CKRS was 13 months for both patients with 1-3 brain metastases and with ≥ 4. This is the only study in the literature to evaluate OS in patients with 1-3 and ≥ 4 brain metastases who were treated with CKRS alone. For groups 1 and 2 patients combined, 119 (79.3%) had LC and 38 (25.3%) had CR. The ANC, ALC, and NLR values are likely predictive of CR and LF outcomes.

  View details for PubMedID 29282442

  View details for PubMedCentralID PMC5741273

• Radiosurgical ablation of spinal cord arteriovenous malformations. Handbook of clinical neurology Sussman, E. S., Adler, J. R., Dodd, R. L. 2017; 143: 175-187

  Abstract

  Spinal cord arteriovenous malformations (SCAVMs) are rare entities that account for less than 20% of spinal masses. These lesions represent a unique clinical challenge, in that surgical or endovascular treatment is often associated with devastating functional consequences. Over the past few decades, radiosurgery has become a well-established treatment modality for SCAVMs, and may be a first-line treatment in many patients afflicted with this devastating disease. This chapter summarizes the data available regarding radiosurgical treatment of SCAVMs.

  View details for DOI 10.1016/B978-0-444-63640-9.00017-5

  View details for PubMedID 28552140

• Radiosurgical ablation of spinal cord arteriovenous malformations. Handbook of clinical neurology Sussman, E. S., Adler, J. R., Dodd, R. L. 2017; 143: 175-187

  Abstract

  Spinal cord arteriovenous malformations (SCAVMs) are rare entities that account for less than 20% of spinal masses. These lesions represent a unique clinical challenge, in that surgical or endovascular treatment is often associated with devastating functional consequences. Over the past few decades, radiosurgery has become a well-established treatment modality for SCAVMs, and may be a first-line treatment in many patients afflicted with this devastating disease. This chapter summarizes the data available regarding radiosurgical treatment of SCAVMs.

  View details for DOI 10.1016/B978-0-444-63640-9.00017-5

  View details for PubMedID 28552140

• Embolization followed by Radiosurgery for the Treatment of Brain Arteriovenous Malformations (AVMs). World neurosurgery Marks, M. P., Marcellus, M. L., Santarelli, J., Dodd, R. L., Do, H. M., Chang, S. D., Adler, J. R., Mlynash, M., Steinberg, G. K. 2016

  Abstract

  Embolization has been proposed to reduce the size of the arteriovenous malformation (AVM) nidus in advance of radiosurgical treatment. Embolization followed by radiosurgery for brain AVMs, however, is controversial.We assessed the impact of embolization on nidal size before radiosurgical treatment and evaluated cure rates and complications by using embolization followed by radiosurgery.A retrospective review of our institutional AVM database identified 91 patients treated from 1995 to 2009 with embolization followed by radiosurgery. Pre- and postembolization AVM volumes were measured with angiography, and the modified radiation-based AVM scores (RBAS) also were calculated pre- and postembolization. RBAS determined from pre-embolization volumes were correlated with postradiosurgical obliteration.Median AVM volume declined from 18.8 mL (interquartile range, 10.2-32.2 mL) to 9.9 mL (3.1-19.2 mL) after embolization, P < 0.00003. Median RBAS scores decreased from 2.6 mL (1.8-3.9 mL) to 1.8 mL (1.0-2.8 mL), P < 0.00003. Two of 91 (2.2%) had new fixed deficits after embolization; however, no patient had new disabling deficits (modified Rankin Scale score >2). A total of 71 of 91 (79%) have had >3 years' follow-up, and 40 (56%) had complete obliteration, with 38 (53%) having excellent outcomes (complete obliteration without neurologic decline). Excellent outcome was seen in 90% of patients with modified RBAS score <1, 66% of patients with score 1-1.5, 50% patients with score 1.5-2, and 43% of patients with score >2.These data suggest that embolization of brain AVMs can safely and effectively reduce the treatment volume before radiosurgery. Combined therapy with embolization and radiosurgery does not appear to adversely affect rates of excellent outcome.

  View details for DOI 10.1016/j.wneu.2016.12.059

  View details for PubMedID 28017742

• 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. 2016: -?

  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 PubMedID 27752881

• The Role of Stereotactic Radiosurgery in the Reirradiation of Metastatic Spinal Tumors. International journal of radiation oncology, biology, physics Ho, C. K., Kumar, K. A., White, E. C., Azoulay, M., Fujimoto, D. K., Aggarwal, S., Gensheimer, M. F., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-?

  View details for DOI 10.1016/j.ijrobp.2016.06.920

  View details for PubMedID 27673858

• A Phase I/II Trial of 5 Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme. International journal of radiation oncology, biology, physics Azoulay, M., Ho, C. K., Fujimoto, D. K., Modlin, L. A., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Nagpal, S., Thomas, R., Recht, L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-E132

  View details for DOI 10.1016/j.ijrobp.2016.06.921

  View details for PubMedID 27673859

• 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

• 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

• 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 Web of Science ID 000373242700012

• 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

• 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

• 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

• The History of CyberKnife Radiosurgery INTRACRANIAL STEREOTACTIC RADIOSURGERY, 2ND EDITION Iyer, A., Chang, S. D., Adler, J. R., Lunsford, L., Sheehan, J. 2016: 16–18

  View details for Web of Science ID 000561992400004

• Innovation in Radiation Oncology Reply INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Brown, J., Adler, J. R. 2015; 93 (4): 935–36

  View details for PubMedID 26530765

• 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 Equipment Development Stifling Innovation in Radiation Oncology? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Brown, J., Adler, J. R. 2015; 92 (4): 713–14

  View details for PubMedID 26104924

• Current Approaches and Recent Developments in the Management of Head and Neck Paragangliomas ENDOCRINE REVIEWS Taieb, D., Kaliski, A., Boedeker, C. C., Martucci, V., Fojo, T., Adler, J. R., Pacak, K. 2014; 35 (5): 795-819

  Abstract

  Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors belonging to the family of pheochromocytoma/paraganglioma neoplasms. Despite advances in understanding the pathogenesis of these tumors, the growth potential and clinical outcome of individual cases remains largely unpredictable. Over several decades, surgical resection has long been the treatment of choice for HNPGLs. However, increasing experience in various forms of radiosurgery has been reported to result in curative-like outcomes, even for tumors localized in the most inaccessible anatomical areas. The emergence of such new therapies challenges the traditional paradigm for the management of HNPGLs. This review will assist and guide physicians who encounter patients with such tumors, either from a diagnostic or therapeutic standpoint. This review will also particularly emphasize current and emerging knowledge in genetics, imaging, and therapeutic options as well as the health-related quality of life for patients with HNPGLs.

  View details for DOI 10.1210/er.2014-1026

  View details for Web of Science ID 000342346200004

  View details for PubMedID 25033281

  View details for PubMedCentralID PMC4167435

• 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

• 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

• 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

• 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

• The future of robotics in radiosurgery. Neurosurgery Adler, J. R. 2013; 72: 8-11

  Abstract

  After emerging from and transforming the practice of neurosurgery, stereotactic radiosurgery is increasingly affecting all surgical disciplines. The first generation of frame-based devices limited radiosurgery treatment to lesions of the brain where the rigidity of the skull provided adequate skeletal purchase. In an effort to surmount such anatomic limitations, robotic radiosurgery was developed. After almost 2 decades of existence, the technology and clinical application of image-guided robotic radiosurgery have evolved considerably, and today a range of treatments with such technology have become commonplace. Nevertheless, the timeless allure of a truly noninvasive, yet highly effective, therapy promises that further refinements in robotic radiosurgery will be forthcoming well into the future.

  View details for DOI 10.1227/NEU.0b013e318271ff20

  View details for PubMedID 23254817

• Untitled INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Ozyar, E., Adler, J. R. 2013; 85 (1): 12

  View details for DOI 10.1016/j.ijrobp.2012.09.011

  View details for Web of Science ID 000312204700026

  View details for PubMedID 23237004

• Long-Term Changes in the Personality and Psychopathological Profile of Opiate Addicts after Nucleus Accumbens Ablative Surgery Are Associated with Treatment Outcome STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Ge, S., Chang, C., Adler, J. R., Zhao, H., Chang, X., Gao, L., Wu, H., Wang, J., Li, N., Wang, X., Gao, G. 2013; 91 (1): 30-44

  Abstract

  To investigate the long-term outcome and changes of the personality and psychopathological profile of opiate addicts after bilateral stereotactic nucleus accumbens (NAc) ablative surgery.60 patients were followed up for 5 years and abstinent status and adverse events were evaluated. NAc lesion volumes and locations were obtained by postoperative MRI scans. The Chinese version of the Eysenck Personality Questionnaire (EPQ-RSC), the Symptom Checklist-90-Revised (SCL-90-R), the Beck Depression Inventory (BDI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the World Health Organization's Quality of Life Questionnaire - Brief Version (WHOQOL-BREF) were administered to the patients before and 5 years after the stereotactic surgery.The total abstinence rate of all patients in their 5th postoperative year was 47.4%. The abstinent patients had a significantly larger lesion volume than the relapsed ones, but a larger lesion volume also increased the risk of adverse events. 5 years after surgery, the abstinent patients showed significant decreases on the Psychoticism (EPQ-P) and Neuroticism (EPQ-N) scores by EPQ-RSC, a significant decline on the Global Severity Index and the subscores in all 10 dimensions by SCL-90-R, significant decreases on the BDI and Y-BOCS scores, and significant improvements on the scores of all domains by WHOQOL-BREF, while for the relapsed patients, only the subscores of obsessive-compulsive by SCL-90-R and the Y-BOCS scores significantly decreased. Postoperative analysis revealed that the abstinent patients had a significantly better score than the relapsed ones by various instruments, and NAc lesion volumes and locations did not correlate with the outcome of any of these instruments.The bilateral ablation of NAc by stereotactic neurosurgery was a feasible method for alleviating psychological dependence on opiate drugs and preventing a relapse. Long-term follow-up suggested that surgery can improve the personality and psychopathological profile of opiate addicts with a trend towards normal levels, provided persistent abstinence can be maintained; relapse, on the other hand, may ruin this effect.

  View details for DOI 10.1159/000343199

  View details for Web of Science ID 000314561100005

  View details for PubMedID 23154203

• The Future of Robotics in Radiosurgery NEUROSURGERY Adler, J. R. 2013; 72: A8-A11

  Abstract

  After emerging from and transforming the practice of neurosurgery, stereotactic radiosurgery is increasingly affecting all surgical disciplines. The first generation of frame-based devices limited radiosurgery treatment to lesions of the brain where the rigidity of the skull provided adequate skeletal purchase. In an effort to surmount such anatomic limitations, robotic radiosurgery was developed. After almost 2 decades of existence, the technology and clinical application of image-guided robotic radiosurgery have evolved considerably, and today a range of treatments with such technology have become commonplace. Nevertheless, the timeless allure of a truly noninvasive, yet highly effective, therapy promises that further refinements in robotic radiosurgery will be forthcoming well into the future.

  View details for DOI 10.1227/NEU.0b013e318271ff20

  View details for Web of Science ID 000315848100003

• A recommendation for training in stereotactic radiosurgery for US neurosurgery residents JOURNAL OF NEUROSURGERY Lunsford, L., Chiang, V., Adler, J. R., Sheehan, J., Friedman, W., Kondziolka, D. 2012; 117: 2–4

  View details for DOI 10.3171/2012.6.GKS12838

  View details for Web of Science ID 000311465300002

  View details for PubMedID 23205781

• 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

• Stereotactic Radiosurgery for the Treatment of Spinal Metastases: Analysis of Tumor Control and Patterns of Failure 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Modlin, L. A., Choi, C. Y. ELSEVIER SCIENCE INC. 2012: S195–S195

  View details for Web of Science ID 000310542900488

• Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Modlin, L. A., Atalar, B., Choi, C. Y., Gibbs, I. C., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G. ELSEVIER SCIENCE INC. 2012: S116–S117

  View details for Web of Science ID 000310542900291

• 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

• 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

• 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

• 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

• A new age of peer reviewed scientific journals. Surgical neurology international Adler, J. R. 2012; 3: 145-?

  Abstract

  The principles of peer reviewed scientific publications date back two and one-half centuries to the origins of Medical Essays and Observations published by the Royal Society of Edinburgh (1731). This year (2012) is notable in that perhaps the most prestigious and best-known medical journal, the New England Journal of Medicine, crossed the second century mark. The methodologies of peer review have undeniably served medicine well and helped to usher in unimaginable advances in human health. Despite such illustrious history, the winds of change are in the air.

  View details for DOI 10.4103/2152-7806.103889

  View details for PubMedID 23230526

  View details for PubMedCentralID PMC3515965

• 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

• Management of Pediatric Intracranial Arteriovenous Malformations: Experience With Multimodality Therapy NEUROSURGERY Darsaut, T. E., Guzman, R., Marcellus, M. L., Edwards, M. S., Tian, L., Do, H. M., Chang, S. D., Levy, R. P., Adler, J. R., Marks, M. P., Steinberg, G. K. 2011; 69 (3): 540-556

  Abstract

  Successful management of pediatric arteriovenous malformations (AVMs) often requires a balanced application of embolization, surgery, and radiosurgery.To describe our experience treating pediatric AVMs.We analyzed 120 pediatric patients (< 18 years of age) with AVMs treated with various combinations of radiosurgery, surgery, and endovascular techniques.Between 1985 and 2009, 76 children with low Spetzler-Martin grade (1-3) and 44 with high-grade (4-5) AVMs were treated. Annual risk of hemorrhage from presentation to initial treatment was 4.0%, decreasing to 3.2% after treatment initiation until confirmed obliteration. Results for AVM obliteration were available in 101 patients. Initial single-modality therapy led to AVM obliteration in 51 of 67 low-grade (76%) and 3 of 34 high-grade (9%) AVMs, improving to 58 of 67 (87%) and 9 of 34 (26%), respectively, with further treatment. Mean time to obliteration was 1.8 years for low-grade and 6.4 years for high-grade AVMs. Disabling neurological complications occurred in 4 of 77 low-grade (5%) and 12 of 43 high-grade (28%) AVMs. At the final clinical follow-up (mean, 9.2 years), 48 of 67 patients (72%) with low-grade lesions had a modified Rankin Scale score (mRS) of 0 to 1 compared with 12 of 34 patients (35%) with high-grade AVMs. On multivariate analysis, significant risk factors for poor final clinical outcome (mRS ≥ 2) included baseline mRS ≥ 2 (odds ratio, 9.51; 95% confidence interval, 3.31-27.37; P < .01), left-sided location (odds ratio, 3.03; 95% confidence interval, 1.11-8.33; P = .03), and high AVM grade (odds ratio, 4.35; 95% confidence interval, 1.28-14.28; P = .02).Treatment of pediatric AVMs with multimodality therapy can substantially improve obliteration rates and may decrease AVM hemorrhage rates. The poor natural history and risks of intervention must be carefully considered when deciding to treat high-grade pediatric AVMs.

  View details for DOI 10.1227/NEU.0b013e3182181c00

  View details for PubMedID 21430584

• 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

• 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

• TECHNIQUE FOR TARGETING ARTERIOVENOUS MALFORMATIONS USING FRAMELESS IMAGE-GUIDED ROBOTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hristov, D., Liu, L., Adler, J. R., Gibbs, I. C., Moore, T., Sarmiento, M., Chang, S. D., Dodd, R., Marks, M., Do, H. M. 2011; 79 (4): 1232-1240

  Abstract

  To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs).DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process.DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm × 145-mm × 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated.The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and technical staff, and possibly reduce the number of cerebral angiograms needed for a particular patient.

  View details for DOI 10.1016/j.ijrobp.2010.05.015

  View details for PubMedID 20801584

• 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

• Frameless image guided robotic radiosurgery of arteriovenous malformation localized on spatially correlated digital subtraction and C-arm CT angiography images JOURNAL OF NEUROINTERVENTIONAL SURGERY Hristov, D., Adler, J. R., Gibbs, I. C., Dodd, R., Marks, M., Chang, S. D., Do, H. M. 2010; 2 (3): 252-254

  Abstract

  A case is reported of frameless image guided robotic radiosurgery for an arteriovenous malformation (AVM). C-arm CT (CACT) and concurrent digital subtraction angiography images were used for AVM localization within the CACT volume. Treatment planning was performed on CT images registered with the CACT dataset. During delivery, a robotic linear accelerator tracked the target based on localization with frequent stereoscopic x-ray imaging. This case demonstrates that a frameless approach to AVM radiosurgery is possible.

  View details for DOI 10.1136/jnis.2009.001941

  View details for PubMedID 21990637

• The 2009 devaluation of radiosurgery and its impact on the neurosurgery-radiation oncology partnership JOURNAL OF NEUROSURGERY Heilbrun, M. P., Adler, J. R. 2010; 113 (1): 10-15

  Abstract

  Neurosurgeons, radiation oncologists, and, increasingly, other surgical specialists recognize that radiosurgery is an important tool for managing selected disorders throughout the body. The partnership between neurosurgeons and radiation oncologists has resulted in collaborative studies that have established the clinical benefits of radiosurgery. Today, however, a range of political and financial issues is straining this relationship and thereby undermining the practice of radiosurgery. Neurosurgeons and radiation oncologists recently restricted the definition of radiosurgery to include only cranial- and spine-focused radiation treatments. Meanwhile, organized radiation oncology decided unilaterally that radiosurgery administered to other parts of the body would be termed stereotactic body radiation therapy. Finally, neurosurgical and radiation oncology coding experts developed new Current Procedural Terminology codes for cranial vault and spine radiosurgery, which were approved for use by the Relative Value Scale Update Committee as of 2009. The authors suggest that the neurosurgery strategy-which included 1) reasserting that all of the tasks of a radiosurgery procedure remain bundled, and 2) agreeing to limit the definition of radiosurgery to cranial vault and spine-has failed neurosurgeons who perform radiosurgery, and it may jeopardize patient access to this procedure in the future. The authors propose that all of the involved medical specialties recognize that the application of image-guided, focused radiation therapy throughout the body requires a partnership between radiation and surgical disciplines. They also urge surgeons to reexamine their coding methods, and they maintain that Current Procedural Terminology codes should be consistent across all of the different specialties involved in these procedures. Finally, surgeons should consider appropriate training in medical physics and radiobiology to perform the tasks involved in these specific procedures; ultimately all parties should receive equivalent reimbursement for similar assigned tasks, whether performed individually or jointly.

  View details for DOI 10.3171/2010.1.JNS09842

  View details for Web of Science ID 000279107300006

  View details for PubMedID 20170303

• Radiosurgery and radiation oncology Response JOURNAL OF NEUROSURGERY Heilbrun, M., Adler, J. R. 2010; 113 (1): 9

  View details for DOI 10.3171/2010.1.JNS091593

  View details for Web of Science ID 000279107300005

• Management of Pediatric Intracranial Arteriovenous Malformations: Experience With Multimodality Therapy Darsaut, T. E., Guzman, R., Marcellus, M. L., Edwards, M. S., Tian, L., Do, H. M., Chang, S. D., Levy, R. P., Adler, J. R., Marks, M. P., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2010: E220

  View details for Web of Science ID 000276106100136

• Can Temporal Lobe Necrosis be Prevented in Patients with Nasopharyngeal/Skull Base Tumors Undergoing a Stereotactic Radiosurgery Boost? A Dose Volume Analysis 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Hara, W., Yun, S., Hsu, A., Soltys, S., Adler, J., Le, Q., Loo, B. W. ELSEVIER SCIENCE INC. 2010: S431–S431

  View details for Web of Science ID 000288775701011

• Survival following Stereotactic Radiosurgery for Newly Diagnosed and Recurrent Glioblastoma Multiforme: A Multicenter Experience 8th Meeting of the International-Stereotactic-Radiosurgery-Society Villavicencio, A. T., Burneikiene, S., Romanelli, P., McNeely, L., Lipani, J. D., Fariselli, L., McIntyre, M., Chang, S. D., Nelson, E. L., Broggi, G., Adler, J. R., Thramann, J. J. KARGER. 2010: 288–299

  View details for Web of Science ID 000288517800026

• Stereotactic Radiosurgery of the Post-operative Resection Cavity for Brain Metastases: Optimization of the Treatment Technique 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Chang, S. D., Adler, J. R., Harsh, G. R., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2010: S7–S7

  View details for Web of Science ID 000288775700015

• 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

• Survival following stereotactic radiosurgery for newly diagnosed and recurrent glioblastoma multiforme: a multicenter experience NEUROSURGICAL REVIEW Villavicencio, A. T., Burneikiene, S., Romanelli, P., Fariselli, L., McNeely, L., Lipani, J. D., Chang, S. D., Nelson, E. L., McIntyre, M., Broggi, G., Adler, J. R. 2009; 32 (4): 417-424

  Abstract

  Despite decades of clinical trials investigating new treatment modalities for glioblastoma multiforme (GBM), there have been no significant treatment advances since the 1980s. Reported median survival times for patients with GBM treated with current modalities generally range from 9 to 19 months. The purpose of the current study is to retrospectively review the ability of CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) radiosurgery to provide local tumor control of newly diagnosed or recurrent GBM. Twenty patients (43.5%) underwent CyberKnife treatment at the time of the initial diagnosis and/or during the first 3 months of their initial clinical management. Twenty-six patients (56.5%) were treated at the time of tumor recurrence or progression. CyberKnife was performed in addition to the traditional therapy. The median survival from diagnosis for the patients treated with CyberKnife as an initial clinical therapy was 11.5 months (range, 2-33) compared to 21 months (range, 8-96) for the patients treated at the time of tumor recurrence/progression. This difference was statistically significant (Kaplan-Meier analysis, P = 0.0004). The median survival from the CyberKnife treatment was 9.5 months (range, 0.25-31 months) and 7 months (range, 1-34 months) for patients in the newly diagnosed and recurrent GBM groups (Kaplan-Meier analysis, P = 0.79), respectively. Cox proportional hazards survival regression analysis demonstrated that survival time did not correlate significantly with treatment parameters (Dmax, Dmin, number of fractions) or target volume. Survival time and recursive partitioning analysis class were not correlated (P = 0.07). Patients with more extensive surgical interventions survived longer (P = 0.008), especially those who underwent total tumor resection vs. biopsy (P = 0.004). There is no apparent survival advantage in using CyberKnife in initial management of glioblastoma patients, and it should be reserved for patients whose tumors recur or progress after conventional therapy.

  View details for DOI 10.1007/s10143-009-0212-6

  View details for Web of Science ID 000269860300009

  View details for PubMedID 19633875

• 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

• Ethical and Scientific Implications of the Globalization of Clinical Research NEW ENGLAND JOURNAL OF MEDICINE Adler, J. R. 2009; 360 (26): 2792

  View details for Web of Science ID 000267286600029

  View details for PubMedID 19553657

• Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course NEUROSURGICAL FOCUS Achrol, A. S., Guzman, R., Varga, M., Adler, J. R., Steinberg, G. K., Chang, S. D. 2009; 26 (5)

  Abstract

  Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are lacking, and controversy exists over previous studies of natural history risk among predominantly ruptured BAVM cohorts. Recent studies have suggested that the majority of BAVMs are now diagnosed as unruptured lesions, and that the risk according to natural history among these lesions may be less than previously assumed. In the first part of this review, the authors discuss available data on the natural history of BAVMs and highlight the need for future studies that aim to develop surrogate biomarkers of disease progression that accurately predict future risk of ICH in BAVMs. The etiology of BAVM remains unknown. Recent studies have suggested a role for genetic factors in the pathogenesis of sporadic BAVM, which is further supported by reports of familial occurrence of BAVM and association with known systemic genetic disorders (such as Osler-Weber-Rendu disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular characterization of BAVM tissue demonstrates a highly angiogenic milieu with evidence of increased endothelial cell turnover. Taken together with a number of reports of de novo BAVM formation, radiographic growth after initial BAVM diagnosis, and regrowth after successful treatment of BAVM, these findings challenge the long-held assumption that BAVMs are static lesions of congenital origin. In the second part of this review, the authors discuss available data on the origins of BAVM and offer insights into future investigations into genetics and endothelial progenitor cell involvement in the pathogenesis of BAVM. Current treatment options for BAVM focus on removal or obliteration of the lesion in an attempt to protect against future ICH risk, including microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS). In the third part of this review, the authors discuss available data on SRS in BAVMs and highlight the need for future studies on the radiobiology of BAVMs, especially in regard to biomarker detection for tracking SRS response during the latency period. Insights from future investigations in BAVM may not only prove important for the development of novel therapies and relevant biomarkers for BAVM, but could also potentially benefit a variety of other disorders involving new vessel formation in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular malformations.

  View details for DOI 10.3171/2009.2.FOCUS0926

  View details for Web of Science ID 000265656800009

  View details for PubMedID 19409010

• 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

• CYBERKNIFE RADIOSURGERY FOR TRIGEMINAL SCHWANNOMAS NEUROSURGERY Sakarnoto, G. T., Borchers, D. J., Xiao, F., Yang, H., Chang, S. D., Adler, J. R. 2009; 64 (2): A14-A18

  Abstract

  Trigeminal schwannomas (TS) are benign tumors that are managed by surgical resection and/or stereotactic radiosurgery. Most radiosurgical series report results using the gamma knife. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is a frameless, robotic stereotactic radiosurgical system. In this series, we report our experience using the CyberKnife in the treatment of TS.We retrospectively reviewed the medical records and diagnostic imaging in 13 consecutive patients with TS who were treated with the CyberKnife from 2003 to 2007. Seven patients had a previous surgical resection. The mean tumor volume was 6.3 mL (range, 0.39-19.98 mL), and the mean marginal dose was 18.5 Gy. Six of the tumors were treated in a single session. The mean clinical follow-up period was 21.8 months (range, 7-53 months).In this series, the tumor control rate was 100%. The average reduction in tumor volume was 45% (range, 14-98%). A modest improvement in facial pain was noted in 4 of the 6 patients who presented with this symptom. One patient had improvement in facial numbness, and another had improvement in pretreatment headaches. One patient developed jaw weakness and facial dysesthesia, and another patient developed asymptomatic radiation necrosis.Although the length of follow-up is limited, we report our initial experience with CyberKnife treatment of TS. Our results demonstrate tumor control rates and clinical outcomes that parallel those of previous reports using gamma knife radiosurgery; however, long-term follow-up studies are needed.

  View details for DOI 10.1227/01.NEU.0000341629.57676.DB

  View details for Web of Science ID 000262797700007

  View details for PubMedID 19165068

• CYBERKNIFE STEREOTACTIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA: ANATOMIC AND MORPHOLOGICAL CONSIDERATIONS NEUROSURGERY Borchers, J. D., Yang, H., Sakamoto, G. T., Howes, G. A., Gupta, G., Chang, S. D., Adler, J. R. 2009; 64 (2): A91-A95

  Abstract

  To search for correlations between specific anatomic, geometric, and morphological properties of the trigeminal nerve and the success of radiosurgical treatment and elimination of facial hypesthesia as a complication.Forty-six patients with at least 6 months of follow-up after CyberKnife (Accuray, Inc., Sunnyvale, CA) rhizotomy were retrospectively reviewed. Patients treated after 2004 were entered into the study after congruity in treatment parameters was established. Anatomic variations regarding the length of each nerve segment and angle of trigeminal nerve takeoff from brainstem to Meckel's cave in the axial and sagittal planes were studied. Dose distribution to surrounding critical structures (brainstem and trigeminal ganglion) was measured. After spatial relationships of involved structures and dose distributions were recorded, their relationship to treatment success, failure, or complication (primarily facial numbness) was tabulated.Forty-five patients (97.2%) experienced pain relief immediately or within weeks. Thirty-four patients maintained excellent outcome. Some degree of facial numbness developed in 18 patients (39.1%) and was mild in 11 of them (Grade II on the Barrow Neurological Institute scale). Patients with a sagittal-angle trigeminal nerve takeoff from the brainstem in the range of 150 to 170 degrees measured from the horizontal plane had a more favorable outcome (P = 0.03) than patients with less obtuse relationships to the proximal nerve origin. Patients who received higher doses of radiation to the brainstem/dorsal root entry zone of the trigeminal nerve experienced a higher rate of posttreatment facial anesthesia.There may be important anatomic and geometric relationships between the treated trigeminal nerve and surrounding critical structures that warrant pretreatment target volume placement and dose distribution considerations.

  View details for DOI 10.1227/01.NEU.0000340795.87734.70

  View details for Web of Science ID 000262797700017

  View details for PubMedID 19165080

• DELAYED RADIATION-INDUCED MYELOPATHY AFTER SPINAL RADIOSURGERY NEUROSURGERY Gibbs, I. C., Patil, C., Gerszten, P. C., Adler, J. R., Burton, S. A. 2009; 64 (2): A67-A72

  Abstract

  Spinal cord injury is arguably the most feared complication in radiotherapy and has historically limited the aggressiveness of spinal tumor treatment. We report a case series of 6 patients treated with radiosurgery who developed delayed myelopathy.Between 1996 and 2005, 1075 patients with benign or malignant spinal tumors were treated by CyberKnife (Accuray, Inc., Sunnyvale, CA) robotic radiosurgery at Stanford University Medical Center and the University of Pittsburgh Medical Center. Patients were followed prospectively with clinical and radiographic assessments at 1- to 6-month intervals. A retrospective review identified patients who developed delayed radiation-induced myelopathy. Six patients (5 women, 1 man) with a mean age of 48 years (range, 25-61 years) developed delayed myelopathy at a mean of 6.3 months (range, 2-9 months) after spinal radiosurgery. Three tumors were metastatic; 3 were benign. The metastases were in the upper to midthoracic spine, whereas the benign tumors were partially in the cervical region. Three cases involved previous radiation therapy.Dose volume histograms were generated for target and critical structures. Clinical and dosimetric factors were analyzed for factors predictive of spinal cord injury. Specific dosimetric factors contributing to this complication could not be identified, but one-half of the patients with myelopathy received spinal cord biological equivalent doses exceeding 8 Gy.Delayed myelopathy after radiosurgery is uncommon with the dose schedules used in this case series. Radiation injury to the spinal cord occurred over a spectrum of dose parameters that prevented identification of specific dosimetric factors contributing to this complication. Primarily, biological equivalent dose estimates were not usable for defining spinal cord tolerance to hypofractionated dose schedules. We recommend limiting the volume of spinal cord treated above an 8-Gy equivalent dose, because half of the complications occurred beyond this level.

  View details for DOI 10.1227/01.NEU.0000341628.98141.86

  View details for Web of Science ID 000262797700014

  View details for PubMedID 19165076

• FORAMINAL NERVE SHEATH TUMORS: INTERMEDIATE FOLLOW-UP AFTER CYBERKNIFE RADIOSURGERY NEUROSURGERY Murovic, J. A., Gibbs, I. C., Chang, S. D., Mobley, B. C., Park, J., Adler, J. R. 2009; 64 (2): A33-A43

  Abstract

  To conduct a retrospective review of outcomes in 15 patients with 18 foraminal tumors, including 17 benign peripheral nerve sheath tumors and 1 malignant peripheral nerve sheath tumor, who underwent CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery at Stanford University Medical Center from 1999 to 2006.Symptoms and findings, neurofibromatosis (NF) association, previous radiation, imaging, dosimetry, tumor volume, central necrosis, and the relation of these factors to outcomes were evaluated.Before treatment, 1 asymptomatic patient had radiculopathic findings, 3 patients experienced local pain with intact neurological examinations, and 7 patients had radiculopathic complaints with intact (1 patient), radiculopathic (4 patients), or radiculomyelopathic examinations (2 patients). Five patients had myelopathic complaints and findings. Three patients had NF1-associated neurofibromas, 1 patient with NF2 had a schwannoma, and 1 patient had a schwannomatosis-related lesion. Two likely radiation-induced lesions, a neurofibroma and a malignant peripheral nerve sheath tumor, were observed. Prescribed doses ranging from 16 to 24 Gy, delivered in 1 to 3 fractions of 6 to 20 Gy, resulted in maximum tumor doses ranging from 20.9 to 30 Gy. Target volumes ranged from 1.36 to 16.9 mL. After radiosurgery, the asymptomatic case remained asymptomatic, and neurological findings improved. Thirteen of 15 symptomatic patients with (12 patients) or without (3 patients) neurological findings improved (3 cases after resection) or remained stable, and 2 patients worsened. Symptoms and examinations remained stable or improved in 8 (80%) of 10 patients with schwannomas and 3 (60%) of 5 patients with neurofibromas. Tumor volumes decreased in 12 (67%) of 18 tumors and increased in 3 tumors. Tumor volumes decreased in 8 of 10 schwannomas and 3 of 7 neurofibromas. Central necrosis developed in 8 (44%) of 18 tumors.CyberKnife radiosurgery resulted in pain relief and functional preservation in selected foraminal peripheral nerve sheath tumors and a malignant peripheral nerve sheath tumor. Symptomatic and neurological improvements were more noticeable with schwannomas. Myelopathic symptoms may necessitate surgical debulking before radiosurgery.

  View details for DOI 10.1227/01.NEU.0000341632.39692.9E

  View details for Web of Science ID 000262797700010

  View details for PubMedID 19165072

• 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

• Spinal Stereotactic Radiosurgery for Metastatic Tumor Recurrence within a Prior External Beam Irradiation Field 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Jackson, P. S., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2009: S126–S126

  View details for Web of Science ID 000270573600270

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spine Tumors 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L. A., Gibbs, I. C. ELSEVIER SCIENCE INC. 2009: S101–S101

  View details for Web of Science ID 000270573600216

• 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

• Technology insight: image-guided robotic radiosurgery - a new approach for noninvasive ablation of spinal lesions NATURE CLINICAL PRACTICE ONCOLOGY Romanelli, P., Adler, J. R. 2008; 5 (7): 405-414

  Abstract

  The need for an effective noninvasive tool to ablate spinal lesions reflects the limitations of traditional surgical and radiotherapeutic approaches. Open surgery is invasive and carries a risk of neurological injury and vertebral column dysfunction. Conventional radiotherapy often has poor clinical efficacy and a risk of neurologic complications. Spinal radiosurgery has been developed to overcome these limitations. This technique consists of precise delivery of high-dose radiation to a spinal target. To spare the delicate and radiation-sensitive spinal cord and to avoid potentially devastating neurological complications, it is essential that the radiation dose decreases rapidly outside of the target. This is accomplished by use of advanced, image-guidance technology, treatment planning software, and robotics. Preliminary data indicate that this approach can achieve high rates of tumor control of spinal and paraspinal lesions and durable reduction of associated vertebral pain without neurological complications. Although spinal radiosurgery is not yet widely practiced, the benefits of this new therapeutic approach are likely to encourage its widespread adoption in coming years.

  View details for DOI 10.1038/ncponc1131

  View details for Web of Science ID 000257138500009

  View details for PubMedID 18477993

• Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma 87th Annual Meeting of the American-Radium-Society Hara, W., Loo, B. W., Goffinet, D. R., Chang, S. D., Adler, J. R., Pinto, H. A., Fee, W. E., Kaplan, M. J., Fischbein, N. J., Le, Q. ELSEVIER SCIENCE INC. 2008: 393–400

  Abstract

  To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

  View details for DOI 10.1016/j.ijrobp.2007.10.027

  View details for Web of Science ID 000255971100013

  View details for PubMedID 18164839

• 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

• Multimodality treatment of posterior fossa arteriovenous malformations - Response JOURNAL OF NEUROSURGERY Kelly, M. E., Guzman, R., Marks, M. P., Do, H. M., Chang, S. D., Adler, J. R., Steinberg, G. K. 2008; 108 (6): 1150-1151

  View details for Web of Science ID 000256245300023

• Multimodality treatment of posterior fossa arteriovenous malformations JOURNAL OF NEUROSURGERY Kelly, M. E., Guzman, R., Sinclair, J., Bell-Stephens, T. E., Bower, R., Hamilton, S., Marks, M. P., Do, H. M., Chang, S. D., Adler, J. R., Levy, R. P., Steinberg, G. K. 2008; 108 (6): 1152-1161

  Abstract

  Posterior fossa arteriovenous malformations (AVMs) are relatively uncommon and often difficult to treat. The authors present their experience with multimodality treatment of 76 posterior fossa AVMs, with an emphasis on Spetzler-Martin Grades III-V AVMs.Seventy-six patients with posterior fossa AVMs treated with radiosurgery, surgery, and endovascular techniques were analyzed.Between 1982 and 2006, 36 patients with cerebellar AVMs, 33 with brainstem AVMs, and 7 with combined cerebellar-brainstem AVMs were treated. Natural history data were calculated for all 76 patients. The risk of hemorrhage from presentation until initial treatment was 8.4% per year, and it was 9.6% per year after treatment and before obliteration. Forty-eight patients had Grades III-V AVMs with a mean follow-up of 4.8 years (range 0.1-18.4 years, median 3.1 years). Fifty-two percent of patients with Grades III-V AVMs had complete obliteration at the last follow-up visit. Three (21.4%) of 14 patients were cured with a single radiosurgery treatment, and 4 (28.6%) of 14 with 1 or 2 radiosurgery treatments. Twenty-one (61.8%) of 34 patients were cured with multimodality treatment. The mean Glasgow Outcome Scale (GOS) score after treatment was 3.8. Multivariate analysis performed in the 48 patients with Grades III-V AVMs showed radiosurgery alone to be a negative predictor of cure (p = 0.0047). Radiosurgery treatment alone was not a positive predictor of excellent clinical outcome (GOS Score 5; p > 0.05). Nine (18.8%) of 48 patients had major neurological complications related to treatment.Single-treatment radiosurgery has a low cure rate for posterior fossa Spetzler-Martin Grades III-V AVMs. Multimodality therapy nearly tripled this cure rate, with an acceptable risk of complications and excellent or good clinical outcomes in 81% of patients. Radiosurgery alone should be used for intrinsic brainstem AVMs, and multimodality treatment should be considered for all other posterior fossa AVMs.

  View details for DOI 10.3171/JNS/2008/108/6/1152

  View details for PubMedID 18518720

• Radiation therapy and CyberKnife radiosurgery in the management of craniopharyngiomas NEUROSURGICAL FOCUS Lee, M., Kalani, M. Y., Cheshier, S., Gibbs, I. C., Adler, J. R., Chang, S. D. 2008; 24 (5)

  Abstract

  Many benign intracranial tumors are amenable to radiotherapy treatment including meningiomas, schwannomas, pituitary tumors, and craniopharyngiomas. The authors present their experience in the treatment of craniopharyngiomas in 16 patients using frameless CyberKnife stereotactic radiosurgery (SRS). The authors discuss the role of radiation therapy in the management of these tumors, and more specifically, the role of CyberKnife SRS.Sixteen patients were treated for residual or recurrent craniopharyngioma between 2000 and 2007 with CyberKnife SRS at Stanford University Medical Center. All patients underwent magnetic resonance imaging and visual and neuroendocrine evaluations before and at regular intervals after SRS. A multisession treatment regimen and a nonisocentric treatment plan for each patient were used with a mean marginal dose of 21.6 Gy and a mean maximal dose of 29.9 Gy.There were adequate clinical data to assess outcomes in 11 of 16 patients. Evaluation of patients between 13 and 71 years of age (mean 34.5 years) with a mean follow-up period of 15.4 months revealed no deterioration in visual or neuroendocrine function. Tumor shrinkage was achieved in 7 of these 11 patients, and tumor control in another 3. One patient had cystic enlargement of the residual tumor.The authors' early experience with the application of CyberKnife SRS to residual or recurrent craniopharyngiomas has been positive; control or shrinkage of the tumor was achieved in 91% of patients, with no visual or neuroendocrine complications. Longer-term follow-up with a larger group of patients is required to fully evaluate the safety and effectiveness of this treatment modality.

  View details for DOI 10.3171/FOC/2008/24/5/E4

  View details for Web of Science ID 000256374300004

  View details for PubMedID 18447743

• The use of TLD and Gafchromic film to assure submillimeter accuracy for image-guided radiosurgery MEDICAL DOSIMETRY Ho, A. K., Gibbs, I. C., Chang, S. D., Main, B., Adler, J. R. 2008; 33 (1): 36-41

  Abstract

  The Cyberknife is an image-guided radiosurgical system. It uses a compact X-band 6-MV linear accelerator mounted on a robotic arm to deliver radiosurgical doses. While routine quality assurance (QA) is essential for any radiosurgery system, QA plays an even more vital role for the Cyberknife system, due to the complexity of the system and the wide range of applications. This paper presents a technique for performing quality assurance using thermoluminescence detectors (TLDs) and Gafchromic films that is intended to be specific for the Cyberknife. However, with minor modification, the proposed method can also be used for QA of other radiosurgery systems. Our initial QA procedure for the CyberKnife utilized a 30 x 30 x 11-cm solid water phantom containing a planar array of slots for 1x 1 x 1-mm TLDs on a 2-mm grid. With the objective of significantly simplifying CyberKnife QA, a new procedure for verification was developed, which uses much fewer TLDs than the prior solid water phantom technique. This new method requires only that the system target dose to the center of a cluster of 7 TLDs. In a prior study with Gafchromic films, conducted at 3 different Cyberknife facilities, the mean clinically relevant error was demonstrated to be 0.7 mm. A similar Gafchromic film analysis replicated these error measurements as part of the present investigation. It cannot be emphasized enough the importance of implementing routine QA to verify the accuracy of any radiosurgery system. Our quality assurance procedure tests the treatment planning system, as well as the entire treatment delivery including the image targeting system and the robot system. Either TLDs or Gafchromic films may be used for QA test of a radiosurgery system. Using both methods for measurement has the advantage independently verifying the accuracy of the system. This approach, which is routinely in used at our institution, has repeatedly confirmed the submillimeter targeting accuracy of our Cyberknife.

  View details for DOI 10.1016/j.meddos.2007.04.009

  View details for Web of Science ID 000253610200006

  View details for PubMedID 18262121

• Cyberknife radiosurgery for trigeminal neuralgia treatment: A preliminary multicenter experience NEUROSURGERY Villavicencio, A. T., Lim, M., Burneikiene, S., Romanelli, P., Adler, J. R., McNeely, L., Chang, S. D., Fariselli, L., McIntyre, M., Bower, R., Broggi, G., Thramann, J. J. 2008; 62 (3): 647-654

  Abstract

  Radiosurgery has gained acceptance as a treatment option for trigeminal neuralgia. We report our preliminary multicenter experience treating trigeminal neuralgia with the CyberKnife (Accuray, Inc., Sunnyvale, CA).A total of 95 patients were treated for idiopathic trigeminal neuralgia between May 2002 and October 2005. Radiosurgical dose and volume parameters were retrospectively analyzed in relation to pain response, complications, and recurrence of symptoms. Optimal treatment parameters were identified for patients who had excellent and sustained pain relief with no complications, including severe or moderate hypesthesia.Excellent pain relief was initially experienced by 64 out of 95 patients (67%). The median time to pain relief was 14 days (range, 0.3-180 d). Posttreatment numbness occurred in 45 (47%) of the patients treated. Using higher radiation doses and treating longer segments of the nerve led to both better pain relief and a higher incidence of hypesthesia. The presence of posttreatment numbness was predictive of better pain relief. The overall rate of complications was 18%. At the mean follow-up time of 2 years, 47 of the 95 patients (50%) had sustained pain relief, all of whom were completely off pain medications.The results of this study suggest the following optimal radiosurgical treatment parameters for treatment of idiopathic trigeminal neuralgia: a median maximal dose of 78 Gy (range, 70-85.4 Gy) and a median length of the nerve treated of 6 mm (range, 5-12 mm).

  View details for DOI 10.1227/01.NEU.0000297129.08066.137

  View details for Web of Science ID 000255268500023

  View details for PubMedID 18425011

• Visual field preservation after multisession cyberknife radiosurgery for perioptic lesions. Neurosurgery Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2008; 62: 733-743

  Abstract

  The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

  View details for DOI 10.1227/01.neu.0000316277.14748.63

  View details for PubMedID 18596432

• 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

• Treatment of intraorbital lesions using the Accuray CyberKnife system. Orbit (Amsterdam, Netherlands) Hirschbein, M. J., Collins, S., Jean, W. C., Chang, S. D., Adler, J. R. 2008; 27 (2): 97-105

  Abstract

  The goal of this study was to better understand the safety and efficacy of CyberKnife image-guided radiosurgery for lesions immediately adjacent to the optic nerves.This retrospective, non-comparative, interventional case series included 16 patients (6 women and 10 men) with lesions located wholly within the orbit. Thirteen cases involved tumors (31% benign and 69% malignant), two cases presented with chronic orbital inflammation and one patient had intraorbital tissue growth secondary to Graves disease. Staged radiosurgical ablation was performed using CyberKnife image-guided technology. The main outcome measures analyzed were change in tumor/neoplasm size, pain, visual field preservation and visual acuity, which were followed for up to 15 months.Twelve patients had a postoperative MRI, which revealed either a decrease or stabilization of tumor size. In the five lymphoma cases there was complete disappearance of the tumor. Pretreatment pain resolved in all 10 patients who reported it before the procedure; improvement in pain typically occurred within 1-2 weeks of radiosurgery. All 16 patients had a visual evaluation performed after the procedure: of these, 15 had no change in their visual field and one reported improvement. Visual acuity was preserved in 13 patients and improved in two, while one patient developed diplopia.Staged CyberKnife radiosurgery is an effective option for the treatment of intraorbital lesions that controls tumor size, relieves pain, and preserves vision. The long-term safety of this treatment remains to be confirmed.

  View details for DOI 10.1080/01676830601177471

  View details for PubMedID 18415869

• Radiosurgery for glomus Jugulare tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lim, M., Bower, R., Nangiana, J. S., Adler, J. R., Chang, S. D. 2007; 6 (5): 419-423

  Abstract

  Results for treating glomus jugulare tumors with radiosurgery have been limited by short follow-up and small number of patients. We report our experience using LINAC or CyberKnife in 21 tumors with a median follow-up of 66 months (Mean follow-up of 60 months). In addition, we have a subset of eight patients that were followed out for more than 10 years. Patients were treated with doses ranging from 1400 cGy to 2700 cGy. We retrospectively assessed patients for efficacy and post treatment side effects. All patients had stable neurological symptoms, and two patients experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this patient received previous external beam radiotherapy. All tumors remained stable or decreased in size by MRI exam. Our results support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors with low morbidity as evidenced by a larger number of patients and long term follow-up.

  View details for Web of Science ID 000250211600007

  View details for PubMedID 17877430

• Cyberknife radiosurgery for lesions of the foramen magnum TECHNOLOGY IN CANCER RESEARCH & TREATMENT Cheshier, S. H., Hanft, S. J., Adler, J. R., Chang, S. D. 2007; 6 (4): 329-335

  Abstract

  The region of the foramen magnum (FM) presents an especially difficult area for therapeutic intervention. Indeed, this location is challenging to access surgically, particularly in the case of intramedullary and anterior lesions. Therefore, the potential for morbidity associated with therapy to the foramen magnum, most frequently in the form of lower cranial nerve deficits, has encouraged the search for methods that can effectively treat lesions of this region while sparing the important neighboring structures. We report our experience in the use of Cyberknife radiosurgery as a treatment option for these lesions. Thirty-five patients (17 men, 18 women; mean age, 51 yr; range, 18-83) with 35 lesions either spanning or approximating the foramen magnum were treated with the CyberKnife radiosurgical system. Histologies were determined either by prior surgery or radiographic criteria and included 25 benign tumors (nine meningiomas, five schwannomas, four neurofibromas, three hemangioblastomas, two ependymomas, one chordomas, and one pilocytic astrocytoma) along with 10 malignant growths (nine metastases and one chondrosarcoma). Twenty-seven (77%) patients presented with at least one sign and/or symptom, while eight (23%) patients were completely asymptomatic. The most common symptoms were headache, limb numbness, and limb/truncal ataxia, all of which were reported by ten (29%) patients. Among cranial neuropathies, CN XII dysfunction was evident in four (11%) patients. The specific fractionation schedule (mean of 1.8 sessions; range, 1-5) was based on the size of the treated lesion. The mean dose utilized was 19 Gy. Radiographic follow-up was obtained for twenty-three (66%) patients. Nine of the twenty-three (39%) were stable in size, ten lesions decreased in size (43%), and four lesions increased in size (17%). In terms of symptom relief, follow-up was collected for twenty-four (69%) patients. Eleven (46%) of these patients experienced no change in their signs or symptoms, while seven (29%) patients experienced improvement. Six (25%) patients witnessed deterioration in their signs and symptoms. Overall, eighteen (75%) patients had their signs and symptoms either stabilize or improve. There were eleven (31%) deaths in our series, eight of which were related to the disease (though not directly related to CyberKnife treatment) and three of which were from unrelated causes. Complications directly related to CyberKnife radiosurgery were noted in four (11%) of the thirty-five patients. These included one case of temporary emesis immediately following treatment, one case of cystic enlargement two months out, and two cases of radiation necrosis (occurring 1.5 yrs and 2.5 yrs out from treatment). Cyberknife radiosurgery can be an effective treatment for many foramen magnum lesions.

  View details for Web of Science ID 000249073000010

  View details for PubMedID 17668941

• Stereotactic radiosurgery - Foreword TECHNOLOGY IN CANCER RESEARCH & TREATMENT Adler, J. R. 2007; 6 (3): 151

  View details for Web of Science ID 000247665500001

• Cyberknife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches. Neurosurgery Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): E580-?

  Abstract

  Cluster headache (CH) is a severe unilateral and periorbital facial pain syndrome that is often associated with autonomic symptoms, including ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, and eyelid edema. We evaluated the treatment of medically refractory CH with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery targeting the pterygopalatine ganglion.A 56-year-old man presented with a 20-year history of medically refractory CH. His symptoms were described as left-sided, severe, stabbing, burning, and often being associated with tearing and rhinorrhea. These headaches occurred virtually every morning and interfered with sleep, lifestyle, and work performance.The patient underwent two pterygopalatine nerve block trials, both of which resulted in the complete relief of headaches for a 24-hour period. Contrast-enhanced computed axial tomography and magnetic resonance imaging scans were fused for target identification and treatment planning. The target volume measured 0.296 cm3 and a single fraction of 45.50 Gy was delivered to the 78% isodose line with a maximum dose of 65 Gy. The patient kept a detailed diary of his headaches and was followed for 12 months after treatment.Results of CyberKnife targeting of the pterygopalatine ganglion in a patient with medically intractable CHs have revealed a significant decrease in the severity and frequency of headaches after a 12-month follow-up period. In addition, the patient has been able to reduce his medication intake, allowing for a significant decrease in medication-related side effects. Longer follow-up periods and additional studies are required to determine the long-term efficacy and late side effects of this treatment strategy.

  View details for PubMedID 17327771

• 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

• 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

• CyberKnife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches NEUROSURGERY Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): 580-581

  Abstract

  Cluster headache (CH) is a severe unilateral and periorbital facial pain syndrome that is often associated with autonomic symptoms, including ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, and eyelid edema. We evaluated the treatment of medically refractory CH with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery targeting the pterygopalatine ganglion.A 56-year-old man presented with a 20-year history of medically refractory CH. His symptoms were described as left-sided, severe, stabbing, burning, and often being associated with tearing and rhinorrhea. These headaches occurred virtually every morning and interfered with sleep, lifestyle, and work performance.The patient underwent two pterygopalatine nerve block trials, both of which resulted in the complete relief of headaches for a 24-hour period. Contrast-enhanced computed axial tomography and magnetic resonance imaging scans were fused for target identification and treatment planning. The target volume measured 0.296 cm3 and a single fraction of 45.50 Gy was delivered to the 78% isodose line with a maximum dose of 65 Gy. The patient kept a detailed diary of his headaches and was followed for 12 months after treatment.Results of CyberKnife targeting of the pterygopalatine ganglion in a patient with medically intractable CHs have revealed a significant decrease in the severity and frequency of headaches after a 12-month follow-up period. In addition, the patient has been able to reduce his medication intake, allowing for a significant decrease in medication-related side effects. Longer follow-up periods and additional studies are required to determine the long-term efficacy and late side effects of this treatment strategy.

  View details for DOI 10.1227/01.NEU.0000255348.33582.DE

  View details for Web of Science ID 000244797000041

• Image-guided robotic radiosurgery for spinal metastases RADIOTHERAPY AND ONCOLOGY Gibbs, I. C., Kamnerdsupaphon, P., Ryu, M., Dodd, R., Kiernan, M., Change, S. D., Adler, J. R. 2007; 82 (2): 185-190

  Abstract

  To determine the effectiveness and safety of image-guided robotic radiosurgery for spinal metastases.From 1996 to 2005, 74 patients with 102 spinal metastases were treated using the CyberKnife at Stanford University. Sixty-two (84%) patients were symptomatic. Seventy-four percent (50/68) of previously treated patients had prior radiation. Using the CyberKnife, 16-25 Gy in 1-5 fractions was delivered. Patients were followed clinically and radiographically for at least 3 months or until death.With mean follow-up of 9 months (range 0-33 months), 36 patients were alive and 38 were dead at last follow-up. No death was treatment related. Eighty-four (84%) percent of symptomatic patients experienced improvement or resolution of symptoms after treatment. Three patients developed treatment-related spinal injury. Analysis of dose-volume parameters and clinical parameters failed to identify predictors of spinal cord injury.Robotic radiosurgery is effective and generally safe for spinal metastases even in previously irradiated patients.

  View details for DOI 10.1016/j.radonc.2006.11.023

  View details for Web of Science ID 000245151400011

  View details for PubMedID 17257702

• A study of the accuracy of CyberKnife spinal radiosurgery using skeletal structure tracking NEUROSURGERY Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): 147-156

  View details for DOI 10.1227/01.NEU.0000249248.55923.EC

  View details for Web of Science ID 000244230600037

• A study of the accuracy of cyberknife spinal radiosurgery using skeletal structure tracking. Neurosurgery Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): ONS147-56

  Abstract

  New technology has enabled the increasing use of radiosurgery to ablate spinal lesions. The first generation of the CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery system required implanted radiopaque markers (fiducials) to localize spinal targets. A recently developed and now commercially available spine tracking technology called Xsight (Accuray, Inc.) tracks skeletal structures and eliminates the need for implanted fiducials. The Xsight system localizes spinal targets by direct reference to the adjacent vertebral elements. This study sought to measure the accuracy of Xsight spine tracking and provide a qualitative assessment of overall system performance.Total system error, which is defined as the distance between the centroids of the planned and delivered dose distributions and represents all possible treatment planning and delivery errors, was measured using a realistic, anthropomorphic head-and-neck phantom. The Xsight tracking system error component of total system error was also computed by retrospectively analyzing image data obtained from eleven patients with a total of 44 implanted fiducials who underwent CyberKnife spinal radiosurgery.The total system error of the Xsight targeting technology was measured to be 0.61 mm. The tracking system error component was found to be 0.49 mm.The Xsight spine tracking system is practically important because it is accurate and eliminates the use of implanted fiducials. Experience has shown this technology to be robust under a wide range of clinical circumstances.

  View details for PubMedID 17297377

• 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

• Stereotactic radiosurgery - an organized neurosurgery-sanctioned definition JOURNAL OF NEUROSURGERY Barnett, G. H., Linskey, M. E., Adler, J. R., Cozzens, J. W., Friedman, W. A., Heilbrun, M. P., Lunsford, L. D., Schulder, M., Sloan, A. E. 2007; 106 (1): 1-5

  View details for Web of Science ID 000243483300001

  View details for PubMedID 17240553

• Irradiation of glomus jugulare tumors: a historical perspective. Neurosurgical focus Li, G., Chang, S., Adler, J. R., Lim, M. 2007; 23 (6): E13-?

  Abstract

  Glomus jugulare tumors are rare, slow-growing vascular lesions that arise from the chief cells of the paraganglia within the jugular bulb. They can be associated with the tympanic branch of the glossopharyngeal nerve (Jacobsen nerve) or the auricular branch of the vagus nerve (Arnold nerve) and are also referred to as chemodectomas or nonchromaffin paragangliomas. Optimal treatment of these histologically benign tumors remains controversial. Surgery remains the treatment of choice, but can carry high morbidity rates. External-beam radiation was originally used for subtotal resections and in patients who were poor surgical candidates; however, radiosurgery has recently been introduced as an effective and safe treatment option for patients with these tumors. In this article the authors discuss the history of radiation therapy for glomus jugulare tumors, focusing on recent radiosurgical results.

  View details for PubMedID 18081478

• CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain. Neurosurgical focus Patil, C. G., Veeravagu, A., Bower, R. S., Li, G., Chang, S. D., Lim, M., Adler, J. R. 2007; 23 (6): E9-?

  Abstract

  Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS).Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy.Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient.The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

  View details for PubMedID 18081486

• 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

• Resampling: An optimization method for inverse planning in robotic radiosurgery MEDICAL PHYSICS Schweikard, A., Schlaefer, A., Adler, J. R. 2006; 33 (11): 4005-4011

  Abstract

  By design, the range of beam directions in conventional radiosurgery are constrained to an isocentric array. However, the recent introduction of robotic radiosurgery dramatically increases the flexibility of targeting, and as a consequence, beams need be neither coplanar nor isocentric. Such a nonisocentric design permits a large number of distinct beam directions to be used in one single treatment. These major technical differences provide an opportunity to improve upon the well-established principles for treatment planning used with GammaKnife or LINAC radiosurgery. With this objective in mind, our group has developed over the past decade an inverse planning tool for robotic radiosurgery. This system first computes a set of beam directions, and then during an optimization step, weights each individual beam. Optimization begins with a feasibility query, the answer to which is derived through linear programming. This approach offers the advantage of completeness and avoids local optima. Final beam selection is based on heuristics. In this report we present and evaluate a new strategy for utilizing the advantages of linear programming to improve beam selection. Starting from an initial solution, a heuristically determined set of beams is added to the optimization problem, while beams with zero weight are removed. This process is repeated to sample a set of beams much larger compared with typical optimization. Experimental results indicate that the planning approach efficiently finds acceptable plans and that resampling can further improve its efficiency.

  View details for DOI 10.1118/1.2357020

  View details for Web of Science ID 000242250800006

  View details for PubMedID 17153380

• Robotic radiosurgery for the treatment of radioresistant brain metastases 7th Congress of the European-Association-for-Neuro-Oncology (EANO) Hara, W., Li, G., Puataweepong, P., Adler, J., Chang, S., Gibbs, I. C. OXFORD UNIV PRESS INC. 2006: 486–86

  View details for Web of Science ID 000240877301365

• Image-guided robotic radiosurgery provides excellent palliation of new and recurrent spinal metastases Gibbs, I. C., Dodd, R., Chang, S., Tupper, L. A., Adler, J. DUKE UNIV PRESS. 2006: 486

  View details for Web of Science ID 000240877301364

• Carotid and vertebral rete mirabile in man presenting with intraparenchymal hemorrhage: a case report. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Li, G., Jayaraman, M. V., Lad, S. P., Adler, J., Do, H., Steinberg, G. K. 2006; 15 (5): 228-231

  Abstract

  Carotid and vertebral rete mirabile is an unusual segmental regression of both the cavernous carotid artery and transdural vertebral arteries with a network of collateral vessels seen rarely in human beings. We present a 57-year-old woman with carotid and vertebral rete mirabile who presented with an acute intraparenchymal hemorrhage. The majority of patients present with subarachnoid hemorrhage or ischemic stroke. This is the first case of a non-Asian patient presenting with an intraparenchymal hemorrhage. In this case report, we describe the clinical and angiographic features of this unusual entity.

  View details for PubMedID 17904080

• Visual field preservation after multisession CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2006; 59 (2): 244-253

  Abstract

  The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

  View details for DOI 10.1227/01.NEU.0000223512.09115.3E

  View details for Web of Science ID 000239763800017

  View details for PubMedID 16883165

• Image-guided radiosurgical ablation of intra- and extra-cranial lesions TECHNOLOGY IN CANCER RESEARCH & TREATMENT Romanelli, P., Schaal, D. W., Adler, J. R. 2006; 5 (4): 421-428

  Abstract

  For decades since its introduction, stereotactic radiosurgery (SRS) was used only to treat intracranial lesions because intracranial targets could be immobilized and located relative to a rigid metal frame affixed to the patient's head. Lesions outside the head were generally not treated with SRS because it is difficult to immobilize extracranial lesions and to attach stereotactic frames elsewhere on the body. Advances in computerized image guidance and robotics allowed the development of systems, such as the CyberKnife SRS System (Accuray, Inc, Sunnyvale, CA), that could target intracranial lesions without the stereotactic frame. Enhancements have resulted in a radiation delivery system that can accurately deliver high-dose, focal radiation to lesions in the spine, chest, and abdomen, even if they move during respiration. In this review we will describe the technical features of frameless SRS systems and briefly review their application to treating intracranial and extracranial lesions, focusing in particular on spinal lesions.

  View details for Web of Science ID 000240089900014

  View details for PubMedID 16866572

• Computer aided robotic radiosurgery. Computer aided surgery Romanelli, P., Schweikard, A., Schlaefer, A., Adler, J. 2006; 11 (4): 161-174

  Abstract

  Radiosurgery involves the precise delivery of sharply collimated high-energy beams of radiation to a distinct target volume along selected trajectories. Historically, accurate targeting required the application of a stereotactic frame, thus limiting the use of this procedure to single treatments of selected intracranial lesions. However, the scope of radiosurgery has undergone a remarkable broadening since the introduction of image-guided robotic radiosurgery. Recent developments in real-time image guidance provide an effective frameless alternative to conventional radiosurgery and allow both the treatment of lesions outside the skull and the possibility of performing hypofractionation. As a consequence, targets in the spine, chest and abdomen can now also be radiosurgically ablated with submillimetric precision. Meanwhile, the combination of image guidance, robotic beam delivery, and non-isocentric inverse planning can greatly enhance the conformality and homogeneity of radiosurgery. The aim of this article is to describe the technological basis of image-guided radiosurgery and provide a perspective on future developments. The current clinical usage of robotic radiosurgery will be reviewed with an emphasis on those applications that may represent a major shift in the therapeutic paradigm.

  View details for PubMedID 17060075

• Multisession cyberknife radiosurgery for intramedullary spinal cord arteriovenous malformations NEUROSURGERY Sinclair, J., Chang, S. D., Gibbs, I. C., Adler, J. R. 2006; 58 (6): 1081-1088

  Abstract

  Intramedullary spinal cord arteriovenous malformations (AVMs) have an unfavorable natural history that characteristically involves myelopathy secondary to progressive ischemia and/or recurrent hemorrhage. Although some lesions can be managed successfully with embolization and surgery, AVM size, location, and angioarchitecture precludes treatment in many circumstances. Given the poor outlook for such patients, and building on the successful experience with radiosurgical ablation of cerebral AVMs, our group at Stanford University has used CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) to treat selected spinal cord AVMs since 1997. In this article, we retrospectively analyze our preliminary experience with this technique.Fifteen patients with intramedullary spinal cord AVMs (nine cervical, three thoracic, and three conus medullaris) were treated by image-guided SRS between 1997 and 2005. SRS was delivered in two to five sessions with an average marginal dose of 20.5 Gy. The biologically effective dose used in individual patients was escalated gradually over the course of this study. Clinical and magnetic resonance imaging follow-up were carried out annually, and spinal angiography was repeated at 3 years.After a mean follow-up period of 27.9 months (range, 3-59 mo), six of the seven patients who were more than 3 years from SRS had significant reductions in AVM volumes on interim magnetic resonance imaging examinations. In four of the five patients who underwent postoperative spinal angiography, persistent AVM was confirmed, albeit reduced in size. One patient demonstrated complete angiographic obliteration of a conus medullaris AVM 26 months after radiosurgery. There was no evidence of further hemorrhage after CyberKnife treatment or neurological deterioration attributable to SRS.This description of CyberKnife radiosurgical ablation demonstrates its feasibility and apparent safety for selected intramedullary spinal cord AVMs. Additional experience is necessary to ascertain the optimal radiosurgical dose and ultimate efficacy of this technique.

  View details for DOI 10.1227/01.NEU.0000215891.25153.BA

  View details for Web of Science ID 000237785900023

  View details for PubMedID 16723887

• 3D target localization using 2D local displacements of skeletal structures in orthogonal X-ray images for image-guided spinal radiosurgery INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY Fu, D., Kuduvalli, G., Maurer, C. R., Allision, J. W., Adler, J. R. 2006; 1: 198-200

  View details for Web of Science ID 000208986900094

• Cyberknife radiosurgery for benign intradural extramedullary spinal tumors NEUROSURGERY Dodd, R. L., Ryu, M. R., Kamnerdsupaphon, P., Gibbs, I. C., Chang, S. D., Adler, J. R. 2006; 58 (4): 674-684

  Abstract

  Microsurgical resection of benign intradural extramedullary spinal tumors is generally safe and successful, but patients with neurofibromatosis, recurrent tumors, multiple lesions, or medical problems that place them at higher surgical risk may benefit from alternatives to surgery. In this prospective study, we analyzed our preliminary experience with image-guided radiosurgical ablation of selected benign spinal neoplasms.Since 1999, CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery was used to manage 51 patients (median age, 46 yr; range, 12-86 yr) with 55 benign spinal tumors (30 schwannomas, nine neurofibromas, 16 meningiomas) at Stanford University Medical Center. Total treatment doses ranged from 1600 to 3000 cGy delivered in consecutive daily sessions (1-5) to tumor volumes that varied from 0.136 to 24.6 cm.Less than 1 year postradiosurgery, three of the 51 patients in this series (one meningioma, one schwannoma, and one neurofibroma) required surgical resection of their tumor because of persistent or worsening symptoms; only one of these lesions was larger radiographically. However, 28 of the 51 patients now have greater than 24 months clinical and radiographic follow-up. After a mean follow-up of 36 months, all of these later lesions were either stable (61%) or smaller (39%). Two patients died from unrelated causes. Radiation-induced myelopathy appeared 8 months postradiosurgery in one patient.Although more patients studied over an even longer follow-up period are needed to determine the long-term efficacy of spinal radiosurgery for benign extra-axial neoplasms, short-term clinical benefits were observed in this prospective analysis. The present study demonstrates that CyberKnife radiosurgical ablation of such tumors is technically feasible and associated with low morbidity.

  View details for DOI 10.1227/01.NEU.0000204128.84742.8F

  View details for Web of Science ID 000237047200026

  View details for PubMedID 16575331

• Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia. Computer aided surgery Lim, M., Cotrutz, C., Romanelli, P., Schaal, D., Gibbs, I., Chang, S. D., Adler, J. R. 2006; 11 (1): 11-20

  Abstract

  Frame-based radiosurgical rhizotomy has been shown in clinical studies to be effective for managing trigeminal neuralgia (TN). To date, however, only a small pilot study has been published for the frameless, image-guided CyberKnife system. We present our preliminary experience with 29 trigeminal neuralgia patients treated with the frameless CyberKnife using X-ray image-guided targeting, a novel CT method for target definition, and non-isocentric planning.All 29 patients failed previous medical therapy and 14 had undergone prior surgical procedures. CT iohexal cisternography was used to identify the 6- to 8-mm segment of nerve to be lesioned. The marginal dose ranged from 60 to 70 Gy (median 66.4 Gy) as defined at an average 79th percentile. The corresponding Dmax varied from 71.4 to 86.4 Gy (median 77.91 Gy).After a median 10-month follow-up, 26 of 29 (90%) patients rated their pain control as excellent and 3 (10%) reported no improvement. Median time to improvement was 6 days. No or only minor progression in numbness was reported by 22 of 29 (76%) patients, 4 of 29 (14%) patients reported worsening, and 3 of 29 (10%) reported the onset of severe ipsilateral facial numbness. Two patients whose target volume inadvertently included the semi-lunar ganglion developed painful dysethesias in the distribution of their numbness.Although the optimal dose and length of nerve to be lesioned are still being refined, this preliminary experience suggests that image-guided robotic radiosurgery can effectively lesion the trigeminal nerve. Further follow-up is needed to determine whether our method has advantages over the more commonly used procedure for radiosurgical trigeminal rhizotomy.

  View details for PubMedID 16531338

• CyberKnife radiosurgery for extremity schwannomas: Technical note and case report STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Lim, M., Adler, J. R. 2006; 84 (2-3): 60-63

  Abstract

  Peripheral nerve sheath tumors are uncommon. Although surgical resection remains the treatment of choice for most symptomatic lesions, the potential for intraoperative injury to the nerve is not insignificant. This concern is of particular relevance in those patients with a genetic proclivity to develop multiple peripheral nerve sheath tumors. Here we report four symptomatic peripheral extremity schwannomas all in 1 patient who was treated with CyberKnife radiosurgery. The radiosurgical Dmax in each case was between 24.4 and 25.32 Gy. At 1-year follow-up, patient symptoms had been ameliorated, no tumor had increased in size and there was no compromise in neurological function. Although this experience is still very preliminary, it represents the first published description of a peripheral nerve sheath tumor being treated with stereotactic radiosurgery.

  View details for DOI 10.1159/000094033

  View details for Web of Science ID 000239562300002

  View details for PubMedID 16790987

• Fast generation of digitally reconstructed radiographs using attenuation fields with application to 2D-3D image registration Medical Imaging 2003 Conference Russakoff, D. B., Rohlfing, T., Mori, K., Rueckert, D., Ho, A., Adler, J. R., Maurer, C. R. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2005: 1441–54

  Abstract

  Generation of digitally reconstructed radiographs (DRRs) is computationally expensive and is typically the rate-limiting step in the execution time of intensity-based two-dimensional to three-dimensional (2D-3D) registration algorithms. We address this computational issue by extending the technique of light field rendering from the computer graphics community. The extension of light fields, which we call attenuation fields (AFs), allows most of the DRR computation to be performed in a preprocessing step; after this precomputation step, DRRs can be generated substantially faster than with conventional ray casting. We derive expressions for the physical sizes of the two planes of an AF necessary to generate DRRs for a given X-ray camera geometry and all possible object motion within a specified range. Because an AF is a ray-based data structure, it is substantially more memory efficient than a huge table of precomputed DRRs because it eliminates the redundancy of replicated rays. Nonetheless, an AF can require substantial memory, which we address by compressing it using vector quantization. We compare DRRs generated using AFs (AF-DRRs) to those generated using ray casting (RC-DRRs) for a typical C-arm geometry and computed tomography images of several anatomic regions. They are quantitatively very similar: the median peak signal-to-noise ratio of AF-DRRs versus RC-DRRs is greater than 43 dB in all cases. We perform intensity-based 2D-3D registration using AF-DRRs and RC-DRRs and evaluate registration accuracy using gold-standard clinical spine image data from four patients. The registration accuracy and robustness of the two methods is virtually identical whereas the execution speed using AF-DRRs is an order of magnitude faster.

  View details for DOI 10.1109/TMI.2005.856749

  View details for Web of Science ID 000232996200005

  View details for PubMedID 16279081

• Visual field preservation after curative multi-modality treatment of occipital lobe artemovenous malformations NEUROSURGERY Sinclair, J., Marks, M. P., Levy, R. P., Adler, J. R., Chang, S. D., Lopez, J. R., Do, H. M., Bell-Stephens, T. E., Lim, M., Steinberg, G. K. 2005; 57 (4): 655-666

  Abstract

  Occipital lobe arteriovenous malformations (AVMs) provide challenging management decisions because of their proximity to the visual cortex and optic radiations. Preservation of visual function throughout treatment is the mainstay of therapeutic planning. We reviewed visual field (VF) outcomes of all patients who received curative treatment for occipital AVMs at Stanford University to evaluate the efficacy of different treatment strategies.We conducted a retrospective review of 55 patients with occipital AVMs treated at Stanford University between 1984 and 2003. Clinical presentation, AVM morphology, and treatment modality were correlated with VF function before and after therapeutic intervention.Of 55 patients, 48 (87.3%) underwent multimodality AVM treatment (7 patients < 3 yr from radiosurgery were excluded from final analysis). One patient died from intracerebral hemorrhage 11 months post-radiosurgery, and five patients deferred further treatment. Forty-two patients (87.5%) were cured, with no residual AVM on final angiography. Curative therapeutic modalities used included embolization alone (2 patients), microsurgery alone (6 patients), microsurgery with radiosurgery (1 patient), microsurgery with embolization (23 patients), radiosurgery with embolization (4 patients), and embolization with radiosurgery and microsurgery (6 patients). Mean follow-up was 5.8 years including treatment. VF follow-up was available in all 42 patients. Twenty-eight (66.7%) patients experienced no change in VFs, six (14.3%) patients with previously abnormal VFs improved, and eight (19.0%) patients showed worsening of VFs (although none developed a new homonymous VF deficit). Duration of treatment was related to VF outcome in patients who presented without a history of AVM-related hemorrhage.Occipital AVMs can be safely cured using multimodality strategies with minimal risk to visual function despite the proximity of these lesions to the visual cortex and associated pathways.

  View details for DOI 10.1227/01.NEU.0000175547.05291.85

  View details for PubMedID 16239877

• Staged stereotactic irradiation for acoustic neuroma NEUROSURGERY Chang, S. D., Gibbs, I. C., Sakamoto, G. T., Lee, E., Oyelese, A., Adler, J. R. 2005; 56 (6): 1254-1261

  Abstract

  Stereotactic radiosurgery has proven effective in the treatment of acoustic neuromas. Prior reports using single-stage radiosurgery consistently have shown excellent tumor control, but only up to a 50 to 73% likelihood of maintaining hearing at pretreatment levels. Staged, frame-based radiosurgery using 12-hour interfraction intervals previously has been shown by our group to achieve excellent tumor control while increasing the rate of hearing preservation at 2 years to 77%. The arrival of CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery now makes it more practical to treat acoustic neuroma with a staged approach. We hypothesize that such factors may further minimize injury of adjacent cranial nerves. In this retrospective study, we report our experience with staged radiosurgery for managing acoustic neuromas.Since 1999, the CyberKnife has been used to treat more than 270 patients with acoustic neuroma at Stanford University. Sixty-one of these patients have now been followed up for a minimum of 36 months and form the basis for the present clinical investigation. Among the treated patients, the mean transverse tumor diameter was 18.5 mm, whereas the total marginal dose was either 18 or 21 Gy using three 6- or 7-Gy fractions. Audiograms and magnetic resonance imaging were obtained at 6-months intervals after treatment for the first 2 years and then annually thereafter.Of the 61 patients with a minimum of 36 months of follow-up (mean, 48 mo), 74% of patients with serviceable hearing (Gardner-Robinson Class 1-2) maintained serviceable hearing at the last follow-up, and no patient with at least some hearing before treatment lost all hearing on the treated side. Only one treated tumor (2%) progressed after radiosurgery; 29 (48%) of 61 decreased in size and 31 (50%) of the 61 tumors were stable. In no patients did new trigeminal dysfunction develop, nor did any patient experience permanent injury to their facial nerve; two patients experienced transient facial twitching that resolved in 3 to 5 months.Although still preliminary, these results indicate that improved tumor dose homogeneity and a staged treatment regimen may improve hearing preservation in acoustic neuroma patients undergoing stereotactic radiosurgery.

  View details for DOI 10.1227/01.NEU.0000159650.79833.2B

  View details for Web of Science ID 000229690300018

  View details for PubMedID 15918941

• CyberKnife radiosurgery for idiopathic trigeminal neuralgia. Neurosurgical focus Lim, M., Villavicencio, A. T., Burneikiene, S., Chang, S. D., Romanelli, P., McNeely, L., McIntyre, M., Thramann, J. J., Adler, J. R. 2005; 18 (5): E9-?

  Abstract

  Gamma knife surgery is an accepted treatment option for trigeminal neuralgia (TN). The safety and efficacy of CyberKnife radiosurgery as a treatment option for TN, however, has not been established.Forty-one patients were treated between May 2002 and September 2004 for idiopathic TN at Stanford University and the Rocky Mountain CyberKnife Center. Patients with atypical pain, multiple sclerosis, or previous radiosurgical treatment or a follow-up duration of less than 6 months were excluded. Patients were evaluated for the level of pain control, response rate, time to pain relief, occurrence of hypesthesia, and time to pain recurrence with respect to the length of the nerve treated and the maximum and the minimum dose to the nerve margin. Thirty-eight patients (92.7%) experienced initial pain relief at a median of 7 days after treatment (range, 24 hours-4 months). Pain control was ranked as excellent in 36 patients (87.8%), moderate in two (4.9%), and three (7.3%) reported no change. Six (15.8%) of the 38 patients with initial relief experienced a recurrence of pain at a median of 6 months (range 2-8 months). Long-term response after a mean follow-up time of 11 months was found in 32 (78%) of 41. Twenty-one patients (51.2%) experienced numbness after treatment.CyberKnife radiosurgery for TN has high rates of initial pain control and short latency to pain relief compared with those reported for other radiosurgery systems. The doses used for treatment were safe and effective. Higher prescribed doses were not associated with improvement in pain relief or recurrence rate. The hypesthesia rate was related to the length of the trigeminal nerve treated.

  View details for PubMedID 15913285

• Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia 14th Meeting of the World-Society-for-Stereotactic-and-Functional-Neurosurgery Romanelli, P., Lim, M., Isidori, A., Chang, S. D., Adler, J. R. MEDIMOND PUBLISHING CO. 2005: 219–223

  View details for Web of Science ID 000233855700038

• Respiration tracking in radiosurgery without fiducials INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY Schweikard, A., Shiomi, H., Adler, J. 2005; 1 (2): 19-27

  Abstract

  In robotic radiosurgery, a focused beam of radiation is moved by a robot arm. We investigated methods for soft-tissue navigation using robotic radiosurgery. In previous work we described a method for real-time tracking based on correlation between the motion of implanted fiducial markers and external skin markers. In this work we extend our method of correlation-based tracking to tracking without implanted fiducials. We propose to use deformation algorithms on CT data sets combined with registration of digitally reconstructed radiographs and intra-treatment X-ray images to obtain intermittent information on the target location. This information is then combined with our basic correlation method to achieve real-time tracking. Our study investigates the feasibility of this approach from the point of view of computing time and required level of user interaction. The term 7D registration is coined to describe the underlying method for performing this task.

  View details for DOI 10.1581/mrcas.2005.010202

  View details for Web of Science ID 000234624700004

  View details for PubMedID 17518375

• Accuray, incorporated: a neurosurgical business case study. Clinical neurosurgery Adler, J. R. 2005; 52: 87-96

  View details for PubMedID 16626058

• Intensity-based 2D-3D spine image registration incorporating a single fiducial marker ACADEMIC RADIOLOGY Russakoff, D. B., Rohlfing, T., Adler, J. R., Maurer, C. R. 2005; 12 (1): 37-50

  Abstract

  The two-dimensional (2D)-three dimensional (3D) registration of a computed tomography image to one or more x-ray projection images has a number of image-guided therapy applications. In general, fiducial marker-based methods are fast, accurate, and robust, but marker implantation is not always possible, often is considered too invasive to be clinically acceptable, and entails risk. There also is the unresolved issue of whether it is acceptable to leave markers permanently implanted. Intensity-based registration methods do not require the use of markers and can be automated because such geometric features as points and surfaces do not need to be segmented from the images. However, for spine images, intensity-based methods are susceptible to local optima in the cost function and thus need initial transformations that are close to the correct transformation.In this report, we propose a hybrid similarity measure for 2D-3D registration that is a weighted combination of an intensity-based similarity measure (mutual information) and a point-based measure using one fiducial marker. We evaluate its registration accuracy and robustness by using gold-standard clinical spine image data from four patients.Mean registration errors for successful registrations for the four patients were 1.3 and 1.1 mm for the intensity-based and hybrid similarity measures, respectively. Whereas the percentage of successful intensity-based registrations (registration error < 2.5 mm) decreased rapidly as the initial transformation got further from the correct transformation, the incorporation of a single marker produced successful registrations more than 99% of the time independent of the initial transformation.The use of one fiducial marker reduces 2D-3D spine image registration error slightly and improves robustness substantially. The findings are potentially relevant for image-guided therapy. If one marker is sufficient to obtain clinically acceptable registration accuracy and robustness, as the preliminary results using the proposed hybrid similarity measure suggest, the marker can be placed on a spinous process, which could be accomplished without penetrating muscle or using fluoroscopic guidance, and such a marker could be removed relatively easily.

  View details for DOI 10.1016/j.acra.2004.09.013

  View details for Web of Science ID 000226820100006

  View details for PubMedID 15691724

• An anthropomorphic phantom study of the accuracy of CyberKnife spinal radiosurgery NEUROSURGERY Cheng, Y., Main, W., Taylor, D., Kuduvalli, G., Apuzzo, M. L., Adler, J. R., Wang, M. Y. 2004; 55 (5): 1138-1146

  Abstract

  Stereotactic radiosurgery requires the highest degree of accuracy in target identification and localization. When targeting paraspinal lesions, the CyberKnife radiosurgical system (Accuray, Inc., Sunnyvale, CA) uses implanted stainless steel fiducials. The purpose of this study was to evaluate the total system for clinically relevant accuracy of this approach.The clinically relevant accuracy of the CyberKnife depends on 1) the accuracy of beam delivery, which in turn represents a compilation of robot and camera image-tracking errors, and 2) the inherent accuracy of target localization that stems from computed tomographic imaging and treatment planning. The clinically relevant accuracy was measured at three different CyberKnife facilities using head and torso phantoms loaded with packs of radiochromic film and expressed as a displacement of the dose contours from the treatment planning.The mean clinically relevant error, as measured at three different CyberKnife facilities, was determined to be 0.7 +/- 0.3 mm, which did not vary with computed tomographic slice thickness in a range of 0.625 to 1.5 mm. The average treatment delivery precision was 0.3 +/- 0.1 mm. Fiducial tracking error was less than 0.3 mm for radial translations up to 14 mm and less than 0.7 mm for rotations up to 4.5 degrees.For the treatment of relatively stationary spinal lesions targeted with fiducial tracking, the CyberKnife system is capable of submillimeter accuracy.

  View details for DOI 10.1227/01.NEU.0000141080.54647.11

  View details for Web of Science ID 000225114000036

  View details for PubMedID 15509320

• Respiration tracking in radiosurgery MEDICAL PHYSICS Schweikard, A., Shiomi, H., Adler, J. 2004; 31 (10): 2738-2741

  Abstract

  Respiratory motion is difficult to compensate for with conventional radiotherapy systems. An accurate tracking method for following the motion of the tumor is of considerable clinical relevance. We investigate methods to compensate for respiratory motion using robotic radiosurgery. In this system the therapeutic beam is moved by a robotic arm, and follows the moving target through a combination of infrared tracking and synchronized x-ray imaging. Infrared emitters are used to record the motion of the patient's skin surface. The position of internal gold fiducials is computed repeatedly during treatment, via x-ray image processing. We correlate the motion between external and internal markers. From this correlation model we infer the placement of the internal target during time intervals where no x-ray images are taken. Fifteen patients with lung tumors have recently been treated with a fully integrated system implementing this new method. The clinical trials confirm our hypothesis that internal motion and external motion are indeed correlated. In a preliminar study we have extended our work to tracking without implanted fiducials, based on algorithms for computing deformation motions and digitally reconstructed radiographs.

  View details for DOI 10.1118/1.1774132

  View details for Web of Science ID 000224743200003

  View details for PubMedID 15543778

• Efficacy and safety of stereotactic radiosurgery for glomus jugulare tumors. Neurosurgical focus Lim, M., Gibbs, I. C., Adler, J. R., Chang, S. D. 2004; 17 (2): E11-?

  Abstract

  Since the mid-1990s the use of radiosurgery for glomus jugulare tumors has grown in popularity. Despite its increased use, follow-up periods for radiosurgery are short and the numbers of patients reported are small. To add to the available information, the authors report their experience with the application of linear accelerator (LINAC) or CyberKnife modalities in 13 patients with 16 tumors.All patients were treated with frame-based LINAC or CyberKnife radiosurgery, with doses ranging from 1400 to 2700 cGy. Patients were retrospectively assessed for posttreatment side effects, which included hearing loss, tongue weakness, and vocal hoarseness. The patients' most recent magnetic resonance (MR) images were also assessed for changes in tumor size. The median follow-up duration was 41 months and the mean follow-up period was 60 months. All tumors remained stable or decreased in size on follow-up MR images. All patients had stable neurological symptoms, and one experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this individual had received previous external-beam radiation therapy.The authors' findings continue to support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors that results in low rates of morbidity.

  View details for PubMedID 15329026

• Ablative procedures for chronic pain NEUROSURGERY CLINICS OF NORTH AMERICA Romanelli, P., Esposito, V., Adler, J. 2004; 15 (3): 335-?

  Abstract

  The advent of neuroaugmentative techniques has reduced the application of neuroablative procedures, especially as regards pain of functional origin. Although intracranial ablative procedures are now rarely performed, spinal ablative procedures, such as anterolateral cordotomies or midline myelotomies, remain important in the management of cancer pain. These procedures produce immediate and satisfactory pain relief with acceptable complication rates. An important future trend will be the application of radiosurgery guided by functional imaging (eg,fMRI, PET) to place such intracranial lesions as cingulotomies or medial thalamotomies.

  View details for DOI 10.1016/j.nec.2004.02.009

  View details for Web of Science ID 000222809500008

  View details for PubMedID 15246341

• Preliminary visual field preservation after staged CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Pham, C. J., Chang, S. D., Gibbs, I. C., Jones, P., Heilbrun, M. P., Adler, J. R. 2004; 54 (4): 799-810

  Abstract

  The limited radiation tolerance of the optic nerves and the optic chiasm makes it a challenge to treat immediately adjacent lesions with radiosurgery. Staged or hypofractionated radiosurgery has the virtue of combining the accuracy and conformality of radiosurgery with the normal tissue-sparing benefits of fractionation. We describe a consecutive series of patients with meningiomas and pituitary adenomas abutting the anterior visual pathways who were treated with staged, image-guided radiosurgery.Thirty-four patients with either meningiomas (20 patients) or pituitary adenomas (14 patients) within 2 mm of the optic apparatus were treated. Several patients had previously been treated with conventional fractionated radiotherapy (5 patients) or subtotal surgical resection (23 patients). Radiosurgery was delivered in two to five stages to a cumulative average marginal dose of 20.0 Gy. Visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months after treatment.The mean follow-up period was 29 months (range, 15-62 mo). Pre- and posttreatment vision was unchanged in 20 patients, improved in 10, and worse in 3. One patient died during follow-up as a result of an unrelated cardiac event. Visual loss was accompanied by tumor progression in two cases. In a third patient with a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, injury to one optic nerve occurred after both a prior course of radiotherapy and three separate sessions of radiosurgery.Staged radiosurgery resulted in high rates of tumor control and preservation of visual function. Ninety-one percent of patients retained their presurgical vision. Staged radiosurgery may be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions adjacent to the optic apparatus.

  View details for DOI 10.1227/01.NEU.0000114261.18723.6A

  View details for Web of Science ID 000220769100004

  View details for PubMedID 15046645

• Radiation tolerance of the spinal cord to staged radiosurgery 6th Meeting of the International-Stereotactic-Radiosurgery-Society Gibbs, I. C., Chang, S. D., Pham, C., Adler, J. R. KARGER. 2004: 22–28

  View details for Web of Science ID 000221523300003

• Fiducial-less respiration tracking in radiosurgery 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) Schweikard, A., Shiomi, H., Fisseler, J., Dotter, M., Berlinger, K., Gehl, H. B., Adler, J. SPRINGER-VERLAG BERLIN. 2004: 992–999

  View details for Web of Science ID 000224322400120

• Temporal pattern of pain relief using cyberknife radiosurgery for trigeminal neuralgia: A preliminary report 6th Meeting of the International-Stereotactic-Radiosurgery-Society Romanelli, P., Chang, S., Gibbs, I. C., Heit, G., Adler, J. R. KARGER. 2004: 181–189

  View details for Web of Science ID 000221523300021

• Quality assurance of the cyberknife fiducial and skull tracking systems 6th Meeting of the International-Stereotactic-Radiosurgery-Society Ho, A., Cotrutz, C., Chang, S. D., Adler, J. R., Gibbs, I. C. KARGER. 2004: 255–259

  View details for Web of Science ID 000221523300028

• Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Le, Q. T., Tate, D., Koong, A., Gibbs, I. C., Chang, S. D., Adler, J. R., Pinto, H. A., Terris, D. J., Fee, W. E., Goffinet, D. R. ELSEVIER SCIENCE INC. 2003: 1046–54

  Abstract

  Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control.Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy.At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension.STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.

  View details for DOI 10.1016/S0360-3016(03)00117-2

  View details for Web of Science ID 000183937500018

  View details for PubMedID 12829140

• The efficacy of linear accelerator stereotactic radiosurgery in treating glomus jugulare tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lim, M., Gibbs, I. C., Adler, J. R., Martin, D. P., Chang, S. D. 2003; 2 (3): 261-265

  Abstract

  Treatment of glomus jugulare tumors with radiosurgery has grown in acceptance since the first reported treatment in 1995, but only a few centers have reported their experiences with limited follow up time. We report our experience with stereotactic radiosurgery in nine patients with ten glomus tumors. All patients were treated either with frame based LINAC or Cyberknife with doses ranging from 1600 cGy to 2500 cGy. Three patients received no previous therapy and one patient received additional external beam radiation for concomitant treatment of carotid body tumors. Patients were then followed for post treatment side effects in addition to change in tumor size by MRI evaluation. The median clinical follow-up time was 26 months (mean 54 months), median radiographic follow-up was 21.5 months (mean 46 months), with a range from 3 to 126 months. The results from our center demonstrated nine of ten tumors to be stable in size by MRI exam, and one tumor which regressed in size. Nine patients had stable neurological symptoms, and one patient experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. Our results continue to support radiosurgery as a suitable form of treatment for glomus jugulare tumors as evidenced by results from this four and a half year follow-up.

  View details for Web of Science ID 000183918300008

  View details for PubMedID 12779355

• Patterns of patient movement during frameless image-guided radiosurgery INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, M. J., Chang, S. D., Gibbs, I. C., Le, Q. T., Hai, J., Kim, D., Martin, D. P., Adler, J. R. 2003; 55 (5): 1400-1408

  Abstract

  Image-guided radiosurgery aligns the treatment beam to the target site by using a radiographic imaging system to locate anatomic landmarks associated with the treatment target. Because the procedure is performed without a rigid frame, the precision of dose alignment can be affected by patient movement. Movement is limited by noninvasive restraints and compensated by remeasuring the target position at short intervals throughout treatment and then realigning the beam. Frameless image-guided radiosurgery has been used at our institution to treat 250 cranial, 23 spinal, 9 lung, and 3 pancreas cases involving malignant and benign tumors as well as vascular malformations. We have analyzed the target position records for all of these cases to assess the frequency, magnitude, and case-by-case patterns of patient movement.The position of the treatment site during image-guided radiosurgery was measured at approximately 1-2-min intervals, on average, using orthogonal amorphous silicon X-ray cameras and an image registration process that determined all six degrees of freedom in the target's position. The change in position from one measurement to the next was indicative of patient movement.The treatment site position along each axis of translation was observed to vary by an average of 0.45 mm for the cranium, 0.53 mm for the cervical spine, 0.53 mm for the lumbar and thoracic spine, 1.06 mm for the lung, and 1.50 mm for the pancreas. Half of all cranial cases showed systematic drifting of the target away from the initial setup position.Using noninvasive restraints and supports, short-term movement of the head and spine during image-guided radiosurgery was limited to a radius of 0.8 mm, which satisfies the prevailing standard for radiosurgical dose alignment precision, but maintaining this margin of error throughout a treatment fraction requires regular monitoring of the target site's position.

  View details for DOI 10.1016/S0360-3016(02)04597-2

  View details for PubMedID 12654453

• CyberKnife radiotherapy for localized prostate cancer: Rationale and technical feasibility TECHNOLOGY IN CANCER RESEARCH & TREATMENT King, C. R., Lehmann, J., Adler, J. R., Hai, J. 2003; 2 (1): 25-29

  Abstract

  There is a clear dose response for localized prostate cancer radiotherapy and there probably is a radiobiological rationale for hypo-fractionation. Combining the two should maximize tumor control and increase the therapeutic ratio. This study examines the rationale and technical feasibility of CyberKnife radiotherapy (a robotic arm-driven linear accelerator) for localized prostate cancer. Its ability to deliver non-coplanar non-isocentric arcs can yield maximally conformal isodoses. It is the only integrated system capable of target position verification and real-time tracking during delivery of conformal stereotactic radiotherapy. Inverse planning with the CyberKnife is used to design a course of radiotherapy for localized prostate cancer. Fiducial markers within the gland are used to verify organ position and track organ motion via an orthogonal pair of electronic x-ray imaging devices and provide real-time feedback correction to the robotic arm during delivery. Conformal isodose curves and dose volume histograms (DVH) are used to compare with an optimized Intensity-Modulated Radiotherapy (IMRT) plan actually delivered to the study patient based upon CT scan-derived organ volumes. The CyberKnife can produce superior DVHs for sparing of rectum and bladder and excellent DVHs for target coverage compared with IMRT, and possesses dose heterogeneities to the same degree as IMRT plans. Because of the significantly longer delivery times required it would be best suited for hypo-fractionated regimens. Such dose regimens might allow for biologically equivalent dose escalation without increased normal tissue toxicity. Since the CyberKnife can verify organ position and motion and correct for this in real-time it is the ideal means of achieving such excellent DVHs without a compromise in doses to normal tissues. These capabilities are essential if one contemplates hypo-fractionated regimens with large dose-per-fraction sizes (>5Gy to 10Gy) and dose-escalation.

  View details for Web of Science ID 000183754900004

  View details for PubMedID 12625751

• Extracranial radiosurgery using the CyberKnife TECHNIQUES IN NEUROSURGERY Romanelli, P., Chang, S. D., Koong, A., Adler, J. R. 2003; 9 (3): 226-231

  View details for Web of Science ID 000186833600015

• Cyberknife radiosurgery for trigeminal neuralgia Meeting of the American-Society-for-Stereotactic-and-Functional-Neurosurgery Romanelli, P., Heit, G., Chang, S. D., Martin, D., Pham, C., Adler, J. KARGER. 2003: 105–9

  Abstract

  We present preliminary results using Cyberknife radiosurgery as a noninvasive treatment for trigeminal neuralgia (TN).Ten patients with medically refractory TN who were deemed unsuitable for conventional surgery underwent Cyberknife radiosurgery using CT cisternography for localization.Pain relief was achieved in 7 patients, in 5 of them within 24-72 h after irradiation.Cyberknife radiosurgery can achieve early-onset pain relief in a subset of TN patients. Improvements using this technique include the absence of a stereotactic ring, potentially improved targeting accuracy produced by CT cisternography and improved dose homogeneity.

  View details for DOI 10.1159/000075112

  View details for Web of Science ID 000188386000016

  View details for PubMedID 14742972

• Intensity-based 2D-3D spine image registration incorporating one fiducial marker 6th International Conference on Medical Image Computing and Computer-Assisted Intervention Russakoff, D. B., Rohlfing, T., Shahidi, R., Kim, D. H., Adler, J. R., Maurer, C. R. SPRINGER-VERLAG BERLIN. 2003: 287–294

  View details for Web of Science ID 000188592600036

• Evaluation of intensity-based 2D-3D spine image registration using clinical gold-standard data 2nd International Workshop on Biomedical Image Registration Russakoff', D. B., Rohlfing, T., Ho, A., Kim, D. H., Shahidi, R., Adler, J. R., Maurer, C. R. SPRINGER-VERLAG BERLIN. 2003: 151–160

  View details for Web of Science ID 000187954800016

• Image-guided spinal stereotactic radiosurgery TECHNIQUES IN NEUROSURGERY Ryu, S. I., Kim, D. H., Martin, D. P., Chang, S. D., Adler, J. R. 2003; 8 (1): 56-64

  View details for Web of Science ID 000181739000008

• Image Guided Stereotactic Radiosurgery for Lesions in Proximity to the Anterior Visual Pathways: A Preliminary Report TECHNOLOGY IN CANCER RESEARCH & TREATMENT Mehta, V. K., Quynh-Thu Le, Q. T., Chang, S. D., Chenery, S., Adler, J. R. 2002; 1 (3): 173-179

  Abstract

  The incidence of optic neuropathy after stereotactic radiosurgery (SRS) is related to the total dose, fraction size, and treatment volume. Theoretically, fractionated SRS can decrease this risk. In this paper, we report our technique for fractionated SRS and assess its potential role in the management of tumors located adjacent to the anterior visual pathways. Since 1997, thirteen patients (median age: 50, range 21-76) with lesions in close proximity to the anterior visual pathways were treated on the CyberKnife image guided SRS system (Accuray, Inc., Sunnyvale, CA). The CyberKnife is a 6MV linear accelerator mounted on a robotic arm which can monitor and adjust to changes in the target position in real time thus eliminating skeletal frame immobilization and allowing for convenient multi-fraction SRS treatments. Magnetic Resonance Imaging (MRI) and computerized tomography (CT) imaging for treatment planning were obtained with the patients head immobilized in an aquaplast mask. After image fusion, the target and critical structures were delineated. Two to five fractions were prescribed with approximately a 24-hour interfraction interval. The patients received 25 Gy in 5 fractions (n=5), 21 Gy in 3 fractions (n=5), or 20 Gy in 2 fractions (n=3) to the 75-95% isodose line. Ten of the thirteen patients had good pretreatment vision. In nearly all instances, the volume of the optic nerve that received 80% of the prescribed dose was < 0.05 cm3. In all instances, the volume of the optic nerve that received 50% of the prescribed dose was 0.03 cm3 of optic nerve. With median follow up of 18 months (range 12 to 54), four patients have had improvement in their vision. No visual deterioration has been observed in any of the other patients. In addition, there has been no tumor progression within the treated field. Fractionated SRS using the CyberKnife is technically feasible and may decrease the risk of optic neuropathy. Greater patient accrual and longer follow up will be necessary to further determine the clinical benefit of this approach.

  View details for Web of Science ID 000208667700002

• Image guided stereotactic radiosurgery for lesions in proximity to the anterior visual pathways: a preliminary report. Technology in cancer research & treatment Mehta, V. K., Lee, Q., Chang, S. D., Cherney, S., Adler, J. R. 2002; 1 (3): 173-180

  Abstract

  The incidence of optic neuropathy after stereotactic radiosurgery (SRS) is related to the total dose, fraction size, and treatment volume. Theoretically, fractionated SRS can decrease this risk. In this paper, we report our technique for fractionated SRS and assess its potential role in the management of tumors located adjacent to the anterior visual pathways. Since 1997, thirteen patients (median age: 50, range 21-76) with lesions in close proximity to the anterior visual pathways were treated on the CyberKnife image guided SRS system (Accuray, Inc., Sunnyvale, CA). The CyberKnife is a 6MV linear accelerator mounted on a robotic arm which can monitor and adjust to changes in the target position in real time thus eliminating skeletal frame immobilization and allowing for convenient multi-fraction SRS treatments. Magnetic Resonance Imaging (MRI) and computerized tomography (CT) imaging for treatment planning were obtained with the patients head immobilized in an aquaplast mask. After image fusion, the target and critical structures were delineated. Two to five fractions were prescribed with approximately a 24-hour interfraction interval. The patients received 25 Gy in 5 fractions (n=5), 21 Gy in 3 fractions (n=5), or 20 Gy in 2 fractions (n=3) to the 75-95% isodose line. Ten of the thirteen patients had good pretreatment vision. In nearly all instances, the volume of the optic nerve that received 80% of the prescribed dose was < 0.05 cm3. In all instances, the volume of the optic nerve that received 50% of the prescribed dose was 0.03 cm3 of optic nerve. With median follow up of 18 months (range 12 to 54), four patients have had improvement in their vision. No visual deterioration has been observed in any of the other patients. In addition, there has been no tumor progression within the treated field. Fractionated SRS using the CyberKnife is technically feasible and may decrease the risk of optic neuropathy. Greater patient accrual and longer follow up will be necessary to further determine the clinical benefit of this approach.

  View details for PubMedID 12622510

• CyberKnife radiosurgery for brain and spinal tumors 2nd International Symposium for Neuroscience Adler, J. R. ELSEVIER SCIENCE BV. 2002: 545–552

  View details for Web of Science ID 000181346500051

• Surgical guidance now and in the future: the next generation of instrumentation. Clinical neurosurgery Adler, J. R. 2002; 49: 105-114

  View details for PubMedID 12506551

• Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions NEUROSURGERY Ryu, S. I., Chang, S. D., Kim, D. H., MURPHY, M. J., Le, Q. T., Martin, D. P., Adler, J. R. 2001; 49 (4): 838-846

  Abstract

  This article demonstrates the technical feasibility of noninvasive treatment of unresectable spinal vascular malformations and primary and metastatic spinal tumors by use of image-guided frameless stereotactic radiosurgery.Stereotactic radiosurgery delivers a high dose of radiation to a tumor volume or vascular malformation in a limited number of fractions and minimizes the dose to adjacent normal structures. Frameless image-guided radiosurgery was developed by coupling an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the therapy beam to treatment sites within the spine or spinal cord, in an outpatient setting, and without the use of frame-based fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Sixteen patients with spinal lesions (hemangioblastomas, vascular malformations, metastatic carcinomas, schwannomas, a meningioma, and a chordoma) were treated with total treatment doses of 1100 to 2500 cGy in one to five fractions by use of image-guided frameless radiosurgery with the CyberKnife system (Accuray, Inc., Sunnyvale, CA). Thirteen radiosurgery plans were analyzed for compliance with conventional radiation therapy.Tests demonstrated alignment of the treatment dose with the target volume within +/-1 mm by use of spine fiducials and the CyberKnife treatment planning system. Tumor patients with at least 6 months of follow-up have demonstrated no progression of disease. Radiographic follow-up is pending for the remaining patients. To date, no patients have experienced complications as a result of the procedure.This experience demonstrates the feasibility of image-guided robotic radiosurgery for previously untreatable spinal lesions.

  View details for PubMedID 11564244

• Current status and optimal use of radiosurgery ONCOLOGY-NEW YORK Chang, S. D., Adler, J. R. 2001; 15 (2): 209-216

  Abstract

  The field of stereotactic radiosurgery is rapidly advancing as a result of both improvements in radiosurgical equipment and better physician understanding of the clinical applications of stereotactic radiosurgery. This article will review recent developments in the field of radiosurgery, including advances in our understanding of the treatment of brain metastases and arteriovenous malformations, as well as the use of stereotactic radiosurgery as a boost following conventional radiation for nasopharyngeal carcinoma to minimize the rate of local recurrence. In addition, improved understanding of the radiobiology of normal neurologic structures adjacent to tumors undergoing radiosurgery has led to the use of fractionated stereotactic radiosurgery for the treatment of acoustic neuromas and tumors bordering the anterior visual pathways. Finally, a breakthrough in radiosurgery involving the development and use of frameless, image-guided stereotactic radiosurgery has allowed for both dose homogeneity and treatment of intracranial lesions based on nonisocentric treatment algorithms that result in improved target conformality. This same frameless radiosurgical system has also expanded the scope of radiosurgery to include the treatment of extracranial lesions throughout the body.

  View details for Web of Science ID 000167070000017

  View details for PubMedID 11252934

• Robotics and radiosurgery - The cyberknife STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Chang, S. D., Adler, J. R. 2001; 76 (3-4): 204-208

  Abstract

  The Cyberknife is a dedicated image-guided robotic radiosurgical device. While clinical results with intracranial lesions are comparable to frame-based radiosurgical techniques, recent experience demonstrates the potential to broadly expand the scope of radiosurgery to many extracranial sites.

  View details for Web of Science ID 000178706800015

  View details for PubMedID 12378098

• Clinical fluoroscopic fiducial-based registration of the vertebral body in spinal neuronavigation Conference on Medicine Meets Virtual Reality 2001 Abbasi, H. R., Grzeszczuk, R., Chin, S., Fahrig, R., Holz, H., Hariri, S., Kim, D., Adler, J., Shahidi, R. I O S PRESS. 2001: 1–7

  Abstract

  We present a system involving a computer-instrumented fluoroscope for the purpose of 3D navigation and guidance using pre-operative diagnostic scans as a reference. The goal of the project is to devise a computer-assisted tool that will improve the accuracy, reduce risk, minimize the invasiveness, and shorten the time it takes to perform a variety of neurosurgical and orthopedic procedures of the spine. For this purpose we propose an apparatus that will track surgical tools and localize them with respect to the patient's 3D anatomy and pre-operative 3D diagnostic scans using intraoperative fluoroscopy for in situ registration and embedded fiducials. Preliminary studies have found a fiducial registration error (FRE) of 1.41 mm and a Target Localization Error (TLE) of 0.48 mm. The resulting system leverages equipment already commonly available in the operating room (OR), providing an important new functionality that is free of many current limitations, while keeping costs contained.

  View details for Web of Science ID 000169103300002

  View details for PubMedID 11317719

• Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for residual or recurrent cranial base and cervical chordomas. Neurosurgical focus Chang, S. D., Martin, D. P., Lee, E., Adler, J. R. 2001; 10 (3): E5-?

  Abstract

  In patients with chordomas the lesions often recur. Furthermore, the location of some chordomas within the base of the skull and the cervical spine can prevent complete resection from being achieved. Previous series have shown that stereotactic radiosurgery can be used as a treatment for residual chordomas with good overall results. The authors review their experience in using linear accelerator (LINAC) stereotactic radiosurgery to treat patients with recurrent and/or residual cranial base and cervical chordomas.Ten patients with chordomas (eight with cranial base and two with cervical lesions [below C-2]) underwent LINAC stereotactic radiosurgery. The mean patient age was 49 years (range 30-73 years). There were seven men and three women. Three patients had undergone one prior surgery, five had undergone two previous surgeries, and two had undergone three prior operations. The mean radiation dose was 19.4 Gy (range 18-24 Gy), and the maximum intratumoral dose averaged 27 Gy (range 24.1-33.1 Gy). The mean secondary collimator size was 14.4 mm (range 7.5-20 mm). The volume of the tumor treated ranged from 1.1 to 21.5 ml. In five patients a standard frame-based LINAC radiosurgery system was used, whereas in the other five the CyberKnife, a frameless image-guided LINAC radiosurgical system, was used. All patients were available for follow-up review, which averaged 4 years (range 1-9 years). Over the course of follow up, one chordoma (10%) was smaller in size, seven were stable, and two chordomas progressed (one in a patient who underwent reoperation and a second course of stereotactic radiosurgery, and the second in a patient who underwent reoperation alone). There were no new neurological deficits noted following radiosurgery in the eight of 10 patients in whom there was no tumor progression, and no patient developed radiation-induced necrosis.Stereotactic radiosurgery can be used to treat patients with recurrent or residual chordomas with excellent tumor control rates. Longer follow-up review in larger series is warranted to confirm these findings.

  View details for PubMedID 16734408

• Development of fluoroscopic registration in spinal neuronavigation 15th International Congress and Exhibition on Computer Assisted Radiology and Surgery Abbasi, H., Grzeszczuk, R., Chin, S., Holz, H., Hairi, S., Badr, R., Kim, D., Adler, J., Shahidi, R. ELSEVIER SCIENCE BV. 2001: 1151–1151

  View details for Web of Science ID 000173844800236

• Development of fluoroscopic registration in spinal neuronavigation Medical Imaging 2001 Conference Abbasi, H., Grzeszczuk, R., Chin, S., Holz, H., Hariri, S., Badr, R., Kim, D., Adler, J., Shahidi, R. SPIE-INT SOC OPTICAL ENGINEERING. 2001: 380–85

  View details for Web of Science ID 000171468900045

• Image-guided extracranial radiosurgery 7th International Meeting on Progress in Radio-Oncology (ICRO/OGRO 7) Sattah, M., Guerrero, T., Chang, S., Martin, D., Le, Q. T., Gibbs, I., Adler, J. MEDIMOND S R L. 2001: 153–162

  View details for Web of Science ID 000176997100020

• Daily low-dose carboplatin as a radiation sensitizer for newly diagnosed malignant glioma JOURNAL OF NEURO-ONCOLOGY Peterson, K., Harsh, G., Fisher, P. G., Adler, J., Le, Q. 2001; 53 (1): 27-32

  Abstract

  Surgical resection followed by local field radiotherapy is currently our most effective approach to treatment for most patients with malignant glioma. Carboplatin chemotherapy has direct cytotoxic effects on glioma cells and acts as a radiation sensitizer to enhance cell killing. Its demonstrated efficacy as a sensitizer in other solid tumors led to this clinical trial of carboplatin as a radiation sensitizer in the treatment of newly diagnosed glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Fourteen patients (nine GBM and five AA) were treated with daily low-dose carboplatin 25 mg/m2 intravenously within 2 h of their fractionated radiotherapy to a total dose of 600 mg/m2. No significant toxicities attributable to this combined therapy were observed. All patients have progressed, with median time to progression of 16 weeks. Eleven patients have died, with median survival of 38 weeks for the entire cohort. Although this regimen appeared safe, there was no benefit in survival time compared to historical patients treated with radiotherapy. The limitations and future potential for the strategy of radiation sensitization are discussed.

  View details for Web of Science ID 000170979800004

  View details for PubMedID 11678427

• Acquired cerebral arteriovenous malformation induced by an anaplastic astrocytoma: An interesting case NEUROLOGICAL RESEARCH Harris, O. A., Chang, S. D., Harris, B. T., Adler, J. R. 2000; 22 (5): 473-477

  Abstract

  High grade gliomas foster an environment rich in angiogenic factors that promote neovascularity. We report a case of a cerebral arteriovenous malformation, which developed in the setting of a high grade astrocytoma. The patient presented with complaints of confusion and left hemiparesis. An initial cerebral angiogram was normal. Repeat angiography six weeks later demonstrated an extremely vascular lesion with arteriovenous shunting involving the right thalamus and occipital lobe. Histopathologic evaluation of open biopsy and autopsy specimens demonstrated a high grade astrocytoma in association with an arteriovenous malformation. Immunohistochemical staining with VEGF was diffusely positive. A possible role for the hyperangiogenic environment of a high grade astrocytoma resulting in the development of an arteriovenous malformation is discussed.

  View details for Web of Science ID 000088406000007

  View details for PubMedID 10935219

• Image-guided radiosurgery for the spine and pancreas. Computer aided surgery MURPHY, M. J., Adler, J. R., Bodduluri, M., Dooley, J., Forster, K., Hai, J., Le, Q., Luxton, G., Martin, D., Poen, J. 2000; 5 (4): 278-288

  Abstract

  A robotic image-guided radiosurgical system has been modified to treat extra-cranial sites using implanted fiducials and skeletal landmarks to locate the treatment targets. The system has been used to treat an artero-venous malformation in the cervical spine, a recurrent schwannoma of the thoracic spine, a metastatic adenocarcinoma of the lumbar spine, and three pancreatic cancers. During each treatment, the image guidance system monitored the position of the target site and relayed the target coordinates to the beam-pointing system at discrete intervals. The pointing system then dynamically aligned the therapy beam with the lesion, automatically compensating for shifts in target position. Breathing-related motion of the pancreas lesions was managed by coordinating beam gating with breath-holding by the patient. The system maintained alignment with the spine lesions to within +/- 0.2 mm on average, and to within +/- 1 mm for the pancreatic tumors. This experience has demonstrated the feasibility of using image-guided robotic radiosurgery outside the cranium.

  View details for PubMedID 11029160

• A comparative statistical error analysis of neuronavigation systems in a clinical setting 3rd International Conference on Medical Image Computing and Computer-Assisted Intervention Abbasi, H., Hariri, S., Martin, D., Kim, D., Adler, J., Steinberg, G., Shahidi, R. SPRINGER-VERLAG BERLIN. 2000: 144–153

  View details for Web of Science ID 000171938700015

• A comparative statistical accuracy analysis of the neuronavigation systems 14th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 2000) Abbasi, H., Martin, D., Adler, J., Steinberg, G., Shahidi, R. ELSEVIER SCIENCE BV. 2000: 985–985

  View details for Web of Science ID 000165685600184

• A fluoroscopic X-ray registration process for three-dimensional surgical navigation 3rd International Conference on Medical Image Computing and Computer-Assisted Intervention Grezeszczuk, R., Chin, S., Fahrig, R., Abassi, H., Holz, H., Kim, D., Adler, J., Shahidi, R. SPRINGER-VERLAG BERLIN. 2000: 551–556

  View details for Web of Science ID 000171938700056

• Image-guided robotic radiosurgery: Clinical and radiographic results with the CyberKnife 4th International-Stereotactic-Radiosurgery-Society Congress Chang, S. D., MURPHY, M. J., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. KARGER. 2000: 23–33

  View details for Web of Science ID 000170815200003

• Robotic motion compensation for respiratory movement during radiosurgery. Computer aided surgery Schweikard, A., Glosser, G., Bodduluri, M., MURPHY, M. J., Adler, J. R. 2000; 5 (4): 263-277

  Abstract

  Tumors in the chest and abdomen move during respiration. The ability of conventional radiation therapy systems to compensate for respiratory motion by moving the radiation source is inherently limited. Since safety margins currently used in radiation therapy increase the radiation dose by a very large amount, an accurate tracking method for following the motion of the tumor is of the utmost clinical relevance. We investigate methods to compensate for respiratory motion using robotic radiosurgery. Thus, the therapeutic beam is moved by a robotic arm, and follows the moving target tumor. To determine the precise position of the moving target, we combine infrared tracking with synchronized X-ray imaging. Infrared emitters are used to record the motion of the patient's skin surface. A stereo X-ray imaging system provides information about the location of internal markers. During an initialization phase (prior to treatment), the correlation between the motions observed by the two sensors (X-ray imaging and infrared tracking) is computed. This model is also continuously updated during treatment to compensate for other, non-respiratory motion. Experiments and clinical trials suggest that robot-based methods can substantially reduce the safety margins currently needed in radiation therapy.

  View details for PubMedID 11029159

• Stereotactic radiosurgery in patients with multiple brain metastases. Neurosurgical focus Chang, S. D., Lee, E., Sakamoto, G. T., Brown, N. P., Adler, J. R. 2000; 9 (2)

  Abstract

  Patients with multiple brain metastases are often treated primarily with fractionated whole-brain radiation therapy (WBRT). In previous reports the authors have shown that patients with four or fewer brain metastases can benefit from stereotactic radiosurgery in addition to fractionated WBRT. In this paper the authors review their experience using linear accelerator stereotactic radiosurgery to treat patients with multiple brain metastases.Fifty-three patients with 149 brain metastases underwent stereotactic radiosurgery. The mean age of patients was 53.1 years (range 20-78 years). There were 23 men and 30 women. The primary tumor location was lung (27 patients), melanoma (10), breast (six), ovary (six), and other (four). All patients harbored at least two metastatic tumors treated with radiosurgery; 27 patients (51%) harbored two lesions, 17 (32%) three lesions, eight (15%) four lesions, and one patient (2%) harbored five lesions. The mean radiation dose administered was 19.6 Gy (range 14-30 Gy), and the mean secondary collimator size was 15.7 mm (range 7.5-40 mm). One hundred thirty-two (89%) of the 149 treated tumors were available for review on magnetic resonance (MR) imaging at 3 months posttreatment. Fifty-two percent were smaller in size, 31% were stable, 9% had increased in size, and 8% had disappeared. New metastatic tumors appeared in 12 (23%) of the 53 patients on MR imaging within 6 months posttreatment. Radiation-induced necrosis occurred at the site of eight (5.4%) of the 149 tumors at 6 months. Seven tumors (4.7%) subsequently required surgical resection for either tumor progression (four cases) or worsening edema from radiation-induced necrosis (three cases). Median actuarial survival was 9.6 months.Stereotactic radiosurgery can be used to treat patients with up to four brain metastases with a 91% rate of either decrease or stabilization in tumor size and a low rate of radiation-induced necrosis. In the authors' study only a small number of patients subsequently required surgical resection of a treated lesion.

  View details for PubMedID 16836289

• Current treatment of patients with multiple brain metastases. Neurosurgical focus Chang, S. D., Adler, J. R. 2000; 9 (2)

  Abstract

  The management of patients with multiple brain metastases remains a difficult challenge for neurosurgeons. This patient population has a poor prognosis when compared with those harboring a solitary brain metastasis, and historically treatment has generally consisted of administering whole-brain radiotherapy once the diagnosis of multiple brain metastases is made. Resection can be useful in a subset of patients with multiple metastases in whom one or two of the lesions are symptomatic, as this may provide rapid reduction of mass effect and edema. Furthermore, the authors of recent studies have shown that stereotactic radiosurgery can be used in certain patients with multiple brain metastases as part of the treatment regimen. In this review the authors outline the treatment options and indications as well as a management strategy for the treatment of patients with multiple brain metastases.

  View details for PubMedID 16836291

• Clinical experience with the CyberKnife at Newport Radiosurgery Center 4th International-Stereotactic-Radiosurgery-Society Congress Chenery, S. G., Massoudi, F., De Salles, A. A., Davis, D. M., CHEHABI, H. H., Adler, J. R. KARGER. 2000: 34–40

  View details for Web of Science ID 000170815200004

• Real-time tracking of the tumor volume in precision radiotherapy and body radiosurgery - A novel approach to compensate for respiratory motion 14th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 2000) Ozhasoglu, C., MURPHY, M. J., Glosser, G., Bodduluri, M., Schweikard, A., Forster, K. M., Martin, D. P., Adler, J. R. ELSEVIER SCIENCE BV. 2000: 691–696

  View details for Web of Science ID 000165685600117

• Volumetric image navigation via a stereotactic endoscope 14th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 2000) Shahidi, R., Wang, B., Khadem, R., Martin, D., Adler, J., Steinberg, G. ELSEVIER SCIENCE BV. 2000: 984–984

  View details for Web of Science ID 000165685600183

• Monte Carlo for the Cyberknife 13th International Conference on the Use of Computers in Radiation Therapy Guerrero, T., Pawlicki, T., Jiang, S. B., Hai, J., Luxton, G., Ozhasoglu, C., Adler, J. R., Ma, C. M. SPRINGER-VERLAG BERLIN. 2000: 344–346

  View details for Web of Science ID 000088386600130

• Treatment of intracranial arteriovenous malformations in the elderly population Chang, S. D., Lopez, J. R., Marks, M. P., Levy, R. P., Adler, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: 325–25

  View details for Web of Science ID 000084589100308

• Image guidance for extra-cranial robotic radiosurgery 14th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 2000) MURPHY, M. J., Adler, J., Bodduluri, M., Glosser, G. ELSEVIER SCIENCE BV. 2000: 685–690

  View details for Web of Science ID 000165685600116

• Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: A preliminary report NEUROSURGERY Poen, J. C., Golby, A. J., Forster, K. M., Martin, D. P., Chinn, D. M., Hancock, S. L., Adler, J. R. 1999; 45 (6): 1299-1305

  Abstract

  Microsurgery and stereotactic radiosurgery (SRS) for vestibular schwannomas are associated with a relatively high incidence of sensorineural hearing loss. A prospective trial of fractionated SRS was undertaken in an attempt to preserve hearing and minimize incidental cranial nerve injury.Thirty-three patients with vestibular schwannomas were treated with 2100 cGy in three fractions during a 24-hour period using conventional frame-based linear accelerator radiosurgery. The median tumor diameter was 20 mm (range, 7-42 mm). Baseline and follow-up evaluations included audiometry and contrast-enhanced magnetic resonance imaging. End points were tumor progression, preservation of serviceable hearing, and treatment-related complications.Thirty-one patients (32 tumors) were assessable for tumor progression and treatment-related complications and 21 patients for preservation of serviceable hearing, with a median follow-up interval of 2 years (range, 0.5-4.0 yr). Tumor regression or stabilization was documented in 30 patients (97%) and tumor progression in 1 (3%). The patient with tumor progression remains asymptomatic and has not required surgical intervention. Five patients (16%) developed trigeminal nerve injury at a median of 6 months (range, 4-12 mo) after SRS; two of these patients had preexisting trigeminal neuropathy. One patient (3%) developed facial nerve injury (House-Brackmann Class 3) 7 months after SRS. Preservation of useful hearing (Gardner-Robertson Class 1-2) was 77% at 2 years. All patients with pretreatment Gardner-Robertson Class 1 to 2 hearing maintained serviceable (Class 1-3) hearing as of their last follow-up examination.Three-fraction SRS with a conventional stereotactic frame is feasible and well tolerated in the treatment of acoustic neuroma. This study demonstrates a high rate of hearing preservation and few treatment-related complications among a relatively high-risk patient cohort (tumors >15 mm or neurofibromatosis Type 2). Longer follow-up will be required to assess the durability of tumor control.

  View details for Web of Science ID 000084092000010

  View details for PubMedID 10598696

• Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: Impact on local control 39th Annual Meeting of ASTRO Tate, D. J., Adler, J. R., Chang, S. D., Marquez, S., Eulau, S. M., Fee, W. E., PINTO, H., Goffinet, D. R. ELSEVIER SCIENCE INC. 1999: 915–21

  Abstract

  Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma.Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy).All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases.Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.

  View details for Web of Science ID 000083624000013

  View details for PubMedID 10571198

• Intracranial nasal dermoid sinus cyst associated with colloid cyst of the third ventricle - Case report and new concepts PEDIATRIC NEUROSURGERY Cheng, M. L., Chang, S. D., Pang, D. L., Adler, J. R. 1999; 31 (4): 201-206

  Abstract

  A case of a 16-year-old male with both a nasal dermoid sinus cyst (NDSC) and a third ventricle colloid cyst is presented. The NDSC was excised via a single-stage combined intracranial-extracranial approach and the third ventricle colloid cyst was resected endoscopically. The pathogenetic theories of NDSC and third ventricle colloid cyst are discussed, and an embryological explanation for the simultaneous development of the two lesions in this patient is explored. This case is best classified among congenital developmental malformations in a category we propose to call 'anterior neuropore corridor defects.'

  View details for Web of Science ID 000085112900007

  View details for PubMedID 10705930

• CARABEAMER: a treatment planner for a robotic radiosurgical system with general kinematics. Medical image analysis Tombropoulos, R. Z., Adler, J. R., Latombe, J. C. 1999; 3 (3): 237-264

  Abstract

  Stereotactic radiosurgery is a minimally invasive procedure that uses a focused beam of radiation as an ablative instrument to destroy brain tumors. To deposit a high dose of radiation in a tumor, while reducing the dose to healthy tissue, a large number of beams are crossfired at the tumor from multiple directions. The treatment planning problem (also called the inverse dosimetry problem) is to compute a set of beams that produces the desired dose distribution. So far its investigation has focused on the generation of isocenter-based treatments in which the beam axes intersect at a common point, the isocenter. However this restriction limits the applicability of the treatments to tumors which have simple shapes. This paper describes CARABEAMER, a new treatment planner for a radiosurgical system in which the radiation source can be arbitrarily positioned and oriented by a six-degree-of-freedom manipulator. This planner uses randomized techniques to guess a promising initial set of beams. It then applies space partitioning and linear programming techniques to compute the energy to be delivered along each beam. Finally, it exploits the results of the linear program to iteratively adapt and improve the beam set. Experimental results obtained with CARABEAMER on both patient and synthetic cases are presented and discussed. These results demonstrate that a radiosurgical system with general kinematics can deliver treatments in which the region receiving a high dose closely matches the shape of the tumor, even in complicated cases. They also suggest new research directions which are discussed at the end of the paper.

  View details for PubMedID 10710294

• Image-guided robotic radiosurgery Neurosurgery Adler, J. R., Murphy, M. J., Chang, S. D., Hancock, S. L. 1999; 44 (6): 1299-306; discussion 1306-7

  Abstract

  PURPOSE: To describe the design and performance of a novel frameless system for radiosurgery. This technology, called image-guided radiosurgery (IGR), eliminates the need for stereotactic frame fixation by relating the identified lesion to radiographic landmarks. CONCEPT: IGR uses a lightweight x-band linear accelerator, computer-controlled robotic arm (Fanuc manipulator [Fanuc Robotics North America, Inc., Rochester Hills, MI]), paired orthogonal x-ray imagers, and a computer workstation that performs rapid image-to-image registration. During radiosurgery, the x-ray imaging system determines the location of the lesion and communicates these coordinates to the robot, which adjusts the pointing of the linear accelerator beam to maintain alignment with the target. RATIONALE: Existing stereotactic techniques require rigid cranial fixation to establish and maintain a system of reference for targeting. Such frames cause pain for the patient, limit the use of fractionation, and necessitate a prolonged period of general anesthesia if children are to be treated. Furthermore, skeletal or any other type of rigid fixation is difficult to achieve beyond the cranium. IGR was designed to overcome these limitations, which are inherent to nearly all current radiosurgical methods. DISCUSSION: Preliminary testing and early clinical experience have demonstrated the practicality and potential of the IGR concept and have identified the most important directions for improvement. For example, an IGR prototype accurately tracked target displacements in three dimensions but showed reduced accuracy when confronted by rotational movements. This observation led to development of a new generation of tracking algorithm that promises to improve tracking in all six dimensions. Further experience indicated that improvements in the quality of the x-ray images were needed to allow the system to locate and treat target sites outside the cranium. Consequently, a new x-ray imaging technology with superior resolution and increased sensitivity has been added to the system. These improvements should make it possible to apply IGR techniques to a variety of targets located throughout the body. This article describes and critiques the components of the IGR and summarizes our preliminary clinical experience.

  View details for PubMedID 10371630

• Image-guided robotic radiosurgery NEUROSURGERY Adler, J. R., MURPHY, M. J., Chang, S. D., Hancock, S. L. 1999; 44 (6): 1299-1306

  View details for Web of Science ID 000080588400068

• Symptomatic vasospasm after resection of a suprasellar pilocytic astrocytoma: Case report and possible pathogenesis SURGICAL NEUROLOGY Chang, S. D., Yap, O. W., Adler, J. R. 1999; 51 (5): 521-526

  Abstract

  Cerebral vasospasm from pathology other than subarachnoid hemorrhage is uncommon. A case of severe vasospasm after resection of a suprasellar pilocytic astrocytoma is reported.A 45-year-old male presented with headache, left facial numbness, bilateral visual loss, and ataxia. Evaluation revealed a large suprasellar tumor, which was resected. Pathologic examination showed pilocytic astrocytoma. The patient developed hemiparesis and aphasia on the fifth postoperative day. Vascular spasm was documented on angiography and by transcranial Doppler.Intraarterial papaverine resulted in moderate angiographic improvement. Attempts to open middle cerebral artery branches with angioplasty were unsuccessful. The patient subsequently developed a left middle cerebral artery infarct.To our knowledge, this is the first description of vasospasm after resection of an astrocytoma. Possible mechanisms contributing to this unusual complication after resection of tumors are discussed.

  View details for Web of Science ID 000080147200021

  View details for PubMedID 10321883

• Percutaneous transfemoral embolization of an indirect carotid-cavernous fistula with cortical venous access to the cavernous sinus JOURNAL OF NEUROSURGERY Bellon, R. J., Liu, A. Y., Adler, J. R., Norbash, A. M. 1999; 90 (5): 959-963

  Abstract

  The authors present the case of a 61-year-old man with an indirect carotid-cavernous fistula (CCF). Many now advocate a primary transvenous approach to deal with such lesions, with packing and thrombosis of the cavernous sinus leading to fistula obliteration. Transvenous access to the cavernous sinus via the inferior petrosal sinus is the usual route of access; both surgical and transfemoral superior ophthalmic vein approaches are also well described. In the case presented, the anatomy of the CCF was unfavorable for these approaches and its dominant venous egress was via a single enlarged arterialized cortical vein. The cavernous sinus was accessed with a transfemoral retrograde approach to the cortical draining vein. Successful CCF embolization was documented radiographically and clinically. To the authors' knowledge, this procedure has not been previously described in the English literature.

  View details for Web of Science ID 000079934600022

  View details for PubMedID 10223466

• Intraoperative video and volumetric image fusion 13th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 99) Shahidi, R., Wang, B., Epitaux, M., Adler, J., Steinberg, G. ELSEVIER SCIENCE BV. 1999: 625–630

  View details for Web of Science ID 000081802300124

• Treatment of cavernous sinus tumors with linear accelerator radiosurgery SKULL BASE SURGERY Chang, S. D., Doty, J. R., Martin, D. P., Hancock, S. L., Adler, J. R. 1999; 9 (3): 195-199

  Abstract

  Since 1989, 79 patients with benign or malignant cavernous sinus tumors, have been treated at Stanford University with linear accelerator (linac) radiosurgery. Radiosurgery has been used as (1) a planned second-stage procedure for residual tumor following surgery, (2) primary treatment for patients whose medical conditions preclude surgery, (3) palliation of malignant lesions, and (4) definitive treatment for small, well-localized, poorly accessible tumors. Mean patient age was 52 years (range, 18 to 88); there were 28 males and 51 females. Sixty-one patients had benign tumors; 18 had malignant tumors. Mean tumor volume was 6.8 cm(3) (range 0.5 to 22.5 cm(3)) covered with an average of 2.3 isocenter (range, 1 to 5). Radiation dose averaged 17.1 Gy. Mean follow-up was 46 months. Tumor control or shrinkage, or both, varied with pathology. Radiographic tumor improvement was most pronounced in malignant lesions, with greater than 85% showing reduction in tumor size; benign tumors (meningiomas and schwannomas) had a 63% control rate and 37% shrinkage rate, with none enlarging. We concluded that stereotactic radiosurgery is a valuable tool in managing cavernous sinus tumors. There was excellent control and stabilization of benign tumors and palliation of malignant lesions.

  View details for Web of Science ID 000083016700004

  View details for PubMedID 17171089

  View details for PubMedCentralID PMC1656740

• Treatment of nasopharyngeal carcinoma: Stereotactic radiosurgical boost following fractionated radiotherapy Meeting of the American-Society-for-Stereotactic-and-Functional-Neurosurgery Chang, S. D., Tate, D. J., Goffinet, D. R., Martin, D. P., Adler, J. R. KARGER. 1999: 64–67

  Abstract

  Treatment of patients with nasopharyngeal carcinoma (NPC) using external beam radiation therapy (XRT) alone results in significant local recurrence. To improve local control, stereotactic radiosurgery (SRS) was used to boost radiation to the primary tumor site following XRT in 23 patients with NPC. SRS was delivered utilizing a frame-based linear accelerator as a boost (range 7-15 Gy, median 12 Gy) following XRT (range 64.8- 70 Gy, median 66 Gy). In all 23 patients (100%) receiving SRS following XRT local control was achieved at a mean follow-up of 21 months (range 2-64 months). There have been no complications of treatment caused by SRS. However, 8 patients (35%) have subsequently developed regional or distant metastases. SRS boost following XRT provides excellent local control in NPC and should be considered for patients with skull base involvement.

  View details for Web of Science ID 000087727900012

  View details for PubMedID 10853100

• Remote-rendered 3D CT angiography (3DCTA) as an intraoperative aid in cerebrovascular neurosurgery. Computer aided surgery Wilkinson, E. P., Shahidi, R., Wang, B., Martin, D. P., Adler, J. R., Steinberg, G. K. 1999; 4 (5): 256-263

  Abstract

  To assess the viability and utility of network-based rendering in the treatment of patients with cerebral aneurysms, we implemented an intraoperative rendering system and protocol using both three-dimensional CT angiography (3DCTA) and perspective volume rendering (PVR).A Silicon Graphics InfiniteReality engine was connected via a Fast Ethernet network to a workstation in the neurosurgical operating room. A protocol was developed to isolate bone and vessels using an appropriate transfer function. Three-dimensional CT angiogram images were volume rendered and transmitted to the workstation using a bandwidth-conserving remote rendering system, and were rotated, cut using clipping planes, and viewed using normal and perspective views. Twelve patients with intracranial aneurysms were examined at surgery using this system.Rendering performance at optimal operating bandwidths (50-60 Mb/s) was excellent, with regeneration of a high-resolution image in less than 1 s. Network performance varied in two cases, slowing image regeneration. Surgeons found the images to be useful as an adjunct to conventional imaging in understanding the morphology of complex aneurysms and their relationship to the skull base.Intraoperative volume rendering using 3DCTA is achievable over a network, can reduce hardware costs by amortizing hardware among multiple users, and provides useful imaging information during the surgical treatment of cerebral aneurysms. Future operating suites may incorporate network-transmitted three-dimensional images as additional sources of imaging information.

  View details for PubMedID 10581523

• Management of the radiosurgery patient: Causes and treatment of adverse sequelae 32nd San Francisco Cancer Symposium Chang, S. D., Adler, J. R. KARGER. 1999: 155–165

  View details for Web of Science ID 000171088100014

• Planning for camera-guided robotic radiosurgery IEEE TRANSACTIONS ON ROBOTICS AND AUTOMATION Schweikard, A., Bodduluri, M., Adler, J. R. 1998; 14 (6): 951-962

  View details for Web of Science ID 000077839500009

• Clinical experience with image-guided robotic radiosurgery (the Cyberknife) in the treatment of brain and spinal cord tumors NEUROLOGIA MEDICO-CHIRURGICA Chang, S. D., Murphy, M., Geis, P., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. 1998; 38 (11): 780-783

  Abstract

  The Cyberknife is an image-guided "frameless" dedicated radiosurgical device. This instrument has several distinct advantages over frame-based systems, including improved patient comfort, increased treatment degrees of freedom, and the potential to target extracranial lesions. Clinical results thus far with respect to the treatment of malignant intracranial tumors has been promising. Additionally, the Cyberknife will likely revolutionize the application of radiosurgery to extracranial sites. A description of the components, treatment planning, and clinical results of the Cyberknife will be reviewed.

  View details for Web of Science ID 000077103400031

  View details for PubMedID 9919913

• Intracranial hypotension presenting with severe encephalopathy - Case report JOURNAL OF NEUROSURGERY Beck, C. E., Rizk, N. W., Kiger, L. T., Spencer, D., Hill, L., Adler, J. R. 1998; 89 (3): 470-473

  Abstract

  A patient with severe and protracted symptoms from intracranial hypotension is described. The patient's presentation was marked by diffuse encephalopathy and profound depression of consciousness. This case report expands the presently known clinical spectrum of this uncommon and generally benign illness. The clinical and laboratory findings typically observed in the syndrome of intracranial hypotension are outlined. The pathophysiological mechanisms of the phenomenon are briefly discussed. Intracranial hypotension is a potentially severe illness with specific treatments that are distinct from the treatment of most neurological diseases. Three cardinal features--postural headache, pachymeningitis, and descent of midline cerebral structures--should prompt the diagnosis.

  View details for Web of Science ID 000075536000019

  View details for PubMedID 9724124

• Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience NEUROSURGERY Chang, S. D., Levy, R. P., Adler, J. R., Martin, D. P., Krakovitz, P. R., Steinberg, G. K. 1998; 43 (2): 213-220

  Abstract

  Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment.All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr).Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery).Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.

  View details for Web of Science ID 000074979500010

  View details for PubMedID 9696072

• Clinical uses of radiosurgery ONCOLOGY-NEW YORK Chang, S. D., Adler, J. R., Hancock, S. L. 1998; 12 (8): 1181-?

  Abstract

  Radiosurgery uses stereotactic targeting methods to precisely deliver highly focused, large doses of radiation to small intracranial tumors and arteriovenous malformations (AVMs). This article reviews the most common clinical applications of radiosurgery and the clinical results reported from a number of series using either a cobalt-60 gamma knife or linear accelerator as radiation sources. Radiosurgery is used to treat malignant tumors, such as selected cases of brain metastases and malignant gliomas (for which stereotactic radiosurgical boosts are utilized in conjunction with fractionated radiation therapy), as well as benign tumors, such as meningiomas, acoustic neuromas, and pituitary adenomas. Treatment of small AVMs is also highly effective. Although radiosurgery has the potential to produce complications, the majority of patients experience clinical improvement with less morbidity than occurs with surgical resection.

  View details for Web of Science ID 000075449300014

  View details for PubMedID 11236310

• Acute hearing loss following fractionated stereotactic radiosurgery for acoustic neuroma - Report of two cases JOURNAL OF NEUROSURGERY Chang, S. D., Poen, J., Hancock, S. L., Martin, D. P., Adler, J. R. 1998; 89 (2): 321-325

  Abstract

  Two cases of acute hearing loss are reported following fractionated stereotactic radiosurgery for acoustic neuroma. Both patients had neurofibromatosis type 2 and were treated with a peripheral tumor dose of 21 Gy delivered in three fractions (7 Gy each) with a minimum interfraction interval of 10 hours. One patient who had previously undergone surgical resection of the treated tumor presented with only rudimentary hearing in the treated ear secondary to an abrupt decrease in hearing prior to treatment. That patient reported total loss of hearing before complete delivery of the third fraction. The second patient had moderately impaired hearing prior to treatment; however, within 10 hours after delivery of the final fraction, he lost all hearing. Both patients showed no improvement in response to glucocorticoid therapy. Possible explanations for this phenomenon are presented.

  View details for Web of Science ID 000074994900022

  View details for PubMedID 9688131

• Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery NEUROSURGERY Chang, S. D., Meisel, J. A., Hancock, S. L., Martin, D. P., McManus, M., Adler, J. R. 1998; 43 (1): 28-34

  Abstract

  Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas.From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo).Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic.Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.

  View details for Web of Science ID 000074274500016

  View details for PubMedID 9657185

• LINAC radiosurgery for cavernous sinus meningiomas STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Chang, S. D., Adler, J. R., Martin, D. P. 1998; 71 (1): 43-50

  Abstract

  Radiosurgery is increasingly used to treat unresectable cavernous sinus tumors. Since 1989, 24 patients with cavernous sinus meningiomas have been treated at Stanford University Medical Center with linear accelerator (LINAC) radiosurgery. The mean age of the patients was 47.8 years (range 28-78). The mean volume treated was 6. 83 cm3 (range 0.45-22.45 cm3), covered with an average of 2.3 isocenters (range 1-5). Radiation dose averaged 17.7 Gy (range 14-20 Gy). This group of patients was retrospectively studied by sending clinical questionnaires to both the patient/family and referring physicians, and reviewing clinic charts. In addition, follow-up imaging studies were obtained to measure residual tumor volume. Follow-up averaged 45.6 months (range 19-80). Tumor control (stabilization) following radiosurgery was noted in 15 (63%) and tumor shrinkage in 9 (37%). Seven meningiomas (29%) showed evidence of central tumor necrosis on MRI imaging 1-3 years after radiosurgery. Neurologic status was improved in 10 patients (42%) and unchanged in 12 patients (50%). There was 1 case of symptomatic brain necrosis and 1 case of radiation edema (asymptomatic). All other complications were transient, including 4 cases of trigeminal hypesthesia and 1 case of worsening diplopia. The 2-year actuarial tumor control rate was 100%. Although follow-up is still short, this experience corroborates prior reports that radiosurgery can be used to treat selected small cavernous sinus meningiomas with good to excellent clinical results and minimal morbidity.

  View details for PubMedID 10072673

• Inverse treatment planning for the CyberKnife 3rd International Stereotactic-Radiosurgery-Society Meeting Tombropoulos, R., Latombe, J. C., Adler, J. R. KARGER LANDES SYSTEMS. 1998: 236–250

  View details for Web of Science ID 000071446800025

• Volumetric image guidance via a stereotactic endoscope 1st International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 98) Shahidi, R., Wang, B., Epitaux, M., Grzeszczuk, R., Adler, J. SPRINGER-VERLAG BERLIN. 1998: 241–252

  View details for Web of Science ID 000082115900026

• Treatment of cranial base meningiomas with linear accelerator radiosurgery NEUROSURGERY Chang, S. D., Adler, J. R. 1997; 41 (5): 1019-1025

  Abstract

  Radiosurgery is increasingly being used to treat cranial base tumors. Since 1989, 55 patients with cranial base meningiomas were treated at Stanford University Medical Center with linear accelerator radiosurgery. An analysis of the clinical and radiographic results of this patient population was the focus of this study.The mean patient age was 55.1 years (range, 28-82 yr). The mean tumor volume was 7.33 cm3 (range, 0.45-27.65 cm3). The radiation dose averaged 18.3 Gy (range, 12-25 Gy), delivered with an average of 2.2 isocenters (range, 1-5). Patients were evaluated retrospectively through clinic notes from follow-up examinations, and residual tumor volume was measured during follow-up imaging studies. The length of follow-up averaged 48.4 months (range, 17-81 mo).Tumor stabilization after radiosurgery was noted in 38 patients (69%), shrinkage in 16 patients (29%), and enlargement in only 1 patient (2%). The results of follow-up magnetic resonance imaging demonstrated decreased central contrast uptake in 11 meningiomas (20%), possibly indicating evidence of central tumor necrosis or tumor vessel obliteration. Neurological status was improved in 15 patients in the series (27%) and unchanged in 34 patients (62%). Three patients (5%) died during the follow-up period, all as a result of causes other than tumor progression. Three patients (5%) developed new permanent symptoms (one patient with seizures, one patient with mild right hemiparesis, and one patient with both vagal and hypoglossal nerve palsy). All other complications were transient, including partial trigeminal nerve palsy in seven patients and diplopia in three patients. The 2-year actuarial tumor control rate was 98%.Although our follow-up period is short, this experience corroborates previous reports that radiosurgery can be used to ablate selected small cranial base meningiomas, with good clinical results and modest morbidity.

  View details for Web of Science ID A1997YE15600007

  View details for PubMedID 9361055

• Radiosurgery for skull base malignancies and nasopharyngeal carcinoma 37th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Cmelak, A. J., Cox, R. S., Adler, J. R., Fee, W. E., Goffinet, D. R. ELSEVIER SCIENCE INC. 1997: 997–1003

  Abstract

  Patients with skull base lesions present a challenging management problem because of intractable symptoms and limited therapeutic options. In 1989 we began treating selected patients with skull base lesions using linac stereotactic radiosurgery. In this study the efficacy and toxicity of this therapeutic modality is investigated.Forty-seven patients with 59 malignant skull base lesions were treated with linac radiosurgery between 1989 and 1995. Eleven patients were treated for primary nasopharyngeal carcinoma using radiosurgery as a boost (7 Gy-16 Gy, median: 12 Gy) to the nasopharynx after a course of fractionated radiotherapy (64.8-70 Gy) without chemotherapy. Another 37 patients were treated for 48 skull base metastases or local recurrences from primary head and neck cancers. Eight of these patients had 12 locally recurrent nasopharyngeal carcinoma lesions occuring 6-96 months after standard radiotherapy, including one patient with nasopharyngeal carcinoma who developed a regional relapse after radiotherapy with a stereotactic boost. Lesion volumes by CT or MRI ranged from 0 to 51 cc (median: 8 cc). Radiation doses of 7.0 Gy-35.0 Gy (median: 20.0 Gy) were delivered to recurrent lesions, usually as a single fraction.All 11 patients who received radiosurgery as a nasopharyngeal boost after standard fractionated radiotherapy remain locally controlled (follow-up: 2-34 months, median: 18). However, one patient required a second radiosurgical treatment for regional relapse outside the initial radiosurgery volume. Thirty-three of 48 (69%) recurrent/metastatic lesions have been locally controlled, including 7 of 12 locally recurrent nasopharyngeal lesions. Follow-up for all patients with recurrent lesions ranged from 1 to 60 months (median: 9 months). Local control did not correlate with lesion size (p = 0.80), histology (p = 0.78), or radiosurgical dose (p = 0.44). Major complications developed after 5 of 59 treatments (8.4%), including three cranial nerve palsies, one CSF leak, and one trismus. Complications were not correlated with radiosurgical volume (p = 0.20), prior skull base irradiation (p = 0.90), or radiosurgery dose > 20 Gy (p = 0.49).Stereotactic radiosurgery is a reasonable treatment modality for patients with skull base malignancies, including patients with primary and recurrent nasopharyngeal carcinoma. The dose distribution obtained with stereotactic radiosurgery provides better homogeneity than an intracavitary implant when used as a boost for nasopharyngeal lesions, especially lesions which involve areas distant to the nasopharyngeal mucosa.

  View details for Web of Science ID A1997XB01200004

  View details for PubMedID 9169805

• The cyberknife: A frameless robotic system for radiosurgery XIIth Meeting of the World Society for Stereotactic and Functional Neurosurgery Adler, J. R., Chang, S. D., MURPHY, M. J., Doty, J., Geis, P., Hancock, S. L. KARGER. 1997: 124–28

  Abstract

  The Cyberknife is a unique instrument for performing frameless stereotactic radiosurgery. Rather than using rigid immobilization, the Cyberknife relies on an image-to-image correlation algorithm for target localization. Furthermore, the system utilizes a novel, light-weight, high-energy radiation source. The authors describe the technical specifications of the Cyberknife and summarize the initial clinical experience.

  View details for Web of Science ID 000074800300019

  View details for PubMedID 9711744

• Robotic radiosurgery with noncylindrical collimators. Computer aided surgery Schweikard, A., Adler, J. R. 1997; 2 (2): 124-134

  Abstract

  In radiosurgery, a moving beam of radiation acts as an ablative surgical instrument. Conventional systems for radiosurgery use a cylindrical radiation beam of fixed cross section. The radiation source can be moved only along simple, standardized paths. A new radiosurgical system based on a six-degree-of-freedom robotic arm has been developed to overcome limitations of conventional systems. We address the following question: Can dose distributions generated by robotic radiosurgery be improved by using noncylindrical radiation beams? This includes static noncylindrical collimators and collimators of adaptable cross section. Geometric methods for planning the shape of the beam in addition to planning beam motion are developed. Design criteria considered in this context are treatment time, radiation penumbra, and transparency of interactive treatment planning. An experimental evaluation compares distributions generated with our new radiosurgical system using cylindrical beams to distributions generated with beams of adaptable, noncylindrical shapes.

  View details for PubMedID 9292264

• Analysis of the proliferative potential of residual tumor after radiosurgery for intraparenchymal brain metastases JOURNAL OF NEUROSURGERY Harris, O. A., Adler, J. R. 1996; 85 (4): 667-671

  Abstract

  A retrospective immunohistochemical study of radiosurgically treated brain metastases was performed to determine whether residual tumor has reduced proliferative potential. The monoclonal antibodies MIB-10 and PC-10 were used as markers for proliferation. The experimental group consisted of pathological specimens obtained from five patients in whom brain metastasis previously had been treated with radiosurgery. Pathological specimens obtained from 10 patients with brain metastases, matched in histology to diseases in the experimental group but untreated by radiosurgery, served as controls. A significant decrease in proliferative indices was observed in metastatic brain cancers after radiosurgery (p < 0.001). These results indicate that the persistent tumor that is present at the site of a metastasis previously treated with radiosurgery is less viable and may not in itself be a significant finding.

  View details for Web of Science ID A1996VJ24700021

  View details for PubMedID 8814172

• Linear accelerator-based stereotaxic radiosurgery for brain metastases: The influence of number of lesions on survival JOURNAL OF CLINICAL ONCOLOGY Joseph, J., Adler, J. R., Cox, R. S., Hancock, S. L. 1996; 14 (4): 1085-1092

  Abstract

  To evaluate the influence of the number of brain metastases on survival after stereotaxic radiosurgery and factors that affect the risk of delayed radiation necrosis after treatment.Between March 1989 and December 1993, 120 consecutive patients underwent linear accelerator-based stereotaxic radiosurgery for brain metastases identified by computed tomography (CT) or magnetic resonance imaging (MRI) scans. The influence of various clinical factors on outcome was assessed using Kaplan-Meier plots of survival from the date of radiosurgery, and univariate and multivariate analyses.The median survival time was 32 weeks. Progressive brain metastases, both local and regional, caused 25 of 104 deaths. Patients with two metastases (n = 30) or a solitary metastasis (n = 70) had equivalent actuarial survival times (P = .07; median, 37 weeks; maximum, 211+ weeks). Patients treated to three or more metastases (n = 20) had significantly shorter survival times (P < .002; median, 14 weeks; maximum, 63 weeks). Prognostic factors associated with prolonged survival included a pretreatment Karnofsky performance status > or = 70% and fewer than three metastases. Delayed radiation necrosis at the treated site developed in 20 patients and correlated with prior or concurrent delivery of whole-brain irradiation and the logarithm of the tumor volume.Survival duration is equivalent for patients with one or two brain metastases and is similar to that reported for patients with a solitary metastasis managed by surgical resection and whole-brain irradiation. Survival after radiosurgery for three or more metastases was similar to that reported for whole-brain irradiation.

  View details for PubMedID 8648361

• Quantified registration error versus the accuracy of registered surfaces for a multimodality surface-based registration system Conference on Image Processing - Medical Imaging 1996 Hemler, P. F., Sumanaweera, T. S., VANDENELSEN, P. A., Napel, S., Adler, J. R. SPIE - INT SOC OPTICAL ENGINEERING. 1996: 348–357

  View details for Web of Science ID A1996BF76L00034

• Preliminary clinical experience with the cyberknife: Image-guided stereotactic radiosurgery 2nd International-Stereotactic-Radiosurgery-Society Meeting Adler, J. R., Cox, R. S. KARGER. 1996: 316–326

  View details for Web of Science ID A1996BE85Y00034

• MR GEOMETRIC DISTORTION CORRECTION FOR IMPROVED FRAME-BASED STEREOTAXIC TARGET LOCALIZATION ACCURACY MAGNETIC RESONANCE IN MEDICINE Sumanaweera, T. S., Glover, G. H., Hemler, P. F., VANDENELSEN, P. A., Martin, D., Adler, J. R., Napel, S. 1995; 34 (1): 106-113

  Abstract

  We present a method to correct the geometric distortion caused by field inhomogeneity in MR images of patients wearing MR-compatible stereotaxic frames. Our previously published distortion correction method derives patient-dependent error maps by computing the phase-difference of 3D images acquired at different TEs. The time difference (delta TE = 4.9 ms at 1.5 T) is chosen such that the water and fat signals are in phase. However, delta TE is long enough to permit phase wraps in the difference images for frequency offsets greater than 205 Hz. Phase unwrapping techniques resolve these only for connected structures; therefore, the phase difference for fiducial rods may be off by multiples of 2 pi relative to the head. We remove this uncertainty by using an additional single 2D phase-different image with delta TE = 1 ms (during which time no phase-wraps are typically expected) to determine the correct multiple of 2 pi for each rod. We tested our method in a cadaver and in a patient using CT as the gold standard. Targets in the frame coordinates were chosen from CT and compared with their locations in MR. Localizing errors using MR compared with CT were as large as 3.7 mm before correction and were reduced to less than 1.11 mm after correction.

  View details for Web of Science ID A1995RF76800015

  View details for PubMedID 7674887

• REGISTRATION ERROR QUANTIFICATION OF A SURFACE-BASED MULTIMODALITY IMAGE FUSION SYSTEM MEDICAL PHYSICS Hemler, P. F., Napel, S., Sumanaweera, T. S., PICHUMANI, R., VANDENELSEN, P. A., Martin, D., Drace, J., Adler, J. R., Perkash, I. 1995; 22 (7): 1049-1056

  Abstract

  This paper presents a new reference data set and associated quantification methodology to assess the accuracy of registration of computerized tomography (CT) and magnetic-resonance (MR) images. Also described is a new semiautomatic surface-based system for registering and visualizing CT and MR images. The registration error of the system was determined using a reference data set that was obtained from a cadaver in which rigid fiducial tubes were inserted prior to imaging. Registration error was measured as the distance between an analytic expression for each fiducial tube in one image set and transformed samples of the corresponding tube obtained from the other. Registration was accomplished by first identifying surfaces of similar anatomic structures in each image set. A transformation that best registered these structures was determined using a nonlinear optimization procedure. Even though the root-mean-square (rms) distance at the registered surfaces was similar to that reported by other groups, it was found that rms distances for the tubes were significantly larger than the final rms distances between the registered surfaces. It was also found that minimizing rms distance at the surface did not minimize rms distance for the tubes.

  View details for Web of Science ID A1995RK26900003

  View details for PubMedID 7565379

• Method for correcting magnetic resonance image distortion for frame-based stereotactic surgery, with preliminary results. Journal of image guided surgery Sumanaweera, T. S., Adler, J. R., Glover, G. H., Hemler, P. F., van den Elsen, P. A., Martin, D., Napel, S. 1995; 1 (3): 151-157

  Abstract

  We previously described a technique for correcting patient-specific magnetic field inhomogeneity spatial distortion in magnetic resonance images (MRI), which was not applicable to patients fitted with MRI-compatible stereotactic fiducial frames. Here we describe an improvement to the technique that permits application for these patients. Measurements with a cadaver head show that this method achieves MRI stereotactic localization accuracy of 1 mm.

  View details for PubMedID 9079440

• A quantitative comparison of residual error for three different multimodality registration techniques 14th International Conference on Information Processing in Medical Imaging Hemler, P. F., VANDENELSEN, P. A., Sumanaweera, T. S., Napel, S., Drace, J., Adler, J. R. KLUWER ACADEMIC PUBL. 1995: 251–262

  View details for Web of Science ID A1995BD56U00021

• A versatile system for multimodality image fusion. Journal of image guided surgery Hemler, P. F., Sumanaweera, T. S., van den Elsen, P. A., Napel, S., Adler, J. 1995; 1 (1): 35-45

  Abstract

  This paper presents a versatile system for registering and visualizing computed tomography and magnetic resonance images. The system utilizes a semi-automatic, surface-based registration strategy which has proven useful for registering a number of different anatomical structures. A triangular mesh approximates surfaces in one image set while a set of surface points is used as a surface approximation in the other set. A non-linear optimization procedure determines the transformation that minimizes the total sum-squared perpendicular distance between triangles of the mesh and surface points. This system has been used without modification to successfully register images of the brain, spine and calcaneus.

  View details for PubMedID 9079425

• CHARACTERIZATION OF SPATIAL DISTORTION IN MAGNETIC-RESONANCE-IMAGING AND ITS IMPLICATIONS FOR STEREOTAXIC SURGERY NEUROSURGERY Sumanaweera, T. S., Adler, J. R., Napel, S., Glover, G. H. 1994; 35 (4): 696-703

  Abstract

  The different sources of spatial distortion in magnetic resonance images are reviewed from the point of view of stereotactic target localization. The extents of the two most complex sources of spatial distortion, gradient field nonlinearities and magnetic field inhomogeneities, are discussed both qualitatively and quantitatively. Several ways by which the spatial distortion resulting from these sources can be minimized are discussed. The clinical relevance of the spatial distortion along with some strategies to minimize the localization errors in magnetic resonance-guided stereotaxy are presented.

  View details for Web of Science ID A1994PH68700046

  View details for PubMedID 7808613

• FAILURE OF INTRACISTERNAL TISSUE-PLASMINOGEN ACTIVATOR TO PREVENT VASOSPASM IN CERTAIN PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE NEUROSURGERY Steinberg, G. K., Vanefsky, M. A., Marks, M. P., Adler, J. R., KOENIG, G. H. 1994; 34 (5): 809-813

  Abstract

  Recent experimental and clinical reports suggest that the intracisternal administration of recombinant tissue plasminogen activator (tPA) within 72 hours of subarachnoid hemorrhage decreases the incidence of severe angiographic and clinical vasospasm. In this report, we present four of eight patients with aneurysmal subarachnoid hemorrhage who developed angiographic and clinical vasospasm with delayed neurological deterioration, despite the use of intracisternal tPA after early aneurysm clipping. One patient did not clear her massive subarachnoid hemorrhage with tPA; one patient had extremely poor collateral flow with occlusion of one cervical internal carotid artery and 80% stenosis of the other cervical internal carotid artery; the other two patients had a subarachnoid hemorrhage 7 to 12 days after their sentinel hemorrhage. Three patients ultimately made excellent or good recoveries, and one was left with hemiparesis. The four other patients treated by this protocol did not develop vasospasm. We conclude that intracisternal tPA may not prevent vasospasm in certain patients. This may relate to inadequate clearing of the subarachnoid clot, pre-existing poor collateral supply, or the occurrence of prior subarachnoid hemorrhage.

  View details for PubMedID 8052377

• TREATMENT PLANNING FOR A RADIOSURGICAL SYSTEM WITH GENERAL KINEMATICS 1994 IEEE International Conference on Robotics and Automation Schweikard, A., Tombropoulos, R., Kavraki, L., Adler, J. R., Latombe, J. C. IEEE COMPUTER SOC. 1994: 1720–1727

  View details for Web of Science ID A1994BA72M00253

• PLANNING, CALIBRATION AND COLLISION-AVOIDANCE FOR IMAGE-GUIDED RADIOSURGERY IEEE/RSJ/GI International Conference on Intelligent Robots and Systems - Advanced Robotic Systems and the Real World Schweikard, A., Bodduluri, M., Tombropoulos, R., Adler, J. R. IEEE. 1994: 554–861

  View details for Web of Science ID A1994BC39W00111

• A SYSTEM FOR MULTIMODALITY IMAGE FUSION 7th Annual IEEE Symposium on Computer-Based Medical Systems Hemler, P. F., Sumanaweera, T., VANDENELSEN, P. A., Napel, S., Adler, J. I E E E, COMPUTER SOC PRESS. 1994: 335–340

  View details for Web of Science ID A1994BB17X00060

• QUANTIFYING MRI GEOMETRIC DISTORTION IN TISSUE MAGNETIC RESONANCE IN MEDICINE Sumanaweera, T., Glover, G., Song, S., Adler, T., Napel, S. 1994; 31 (1): 40-47

  Abstract

  We present a method to quantify the MR field inhomogeneity geometric distortion to subpixel accuracy without using objects of known dimensions and without using an external standard such as CT. Our method may be used to quantify the geometric accuracy of MR images of anatomical structures of unknown geometry and also to test any geometry correction scheme. We have quantified the distortion in a tissue phantom and found the largest error to be approximately 2.8 pixels (1.8 mm) for Bo = 1.5 T, G = 3.13 mT/m and FOV = 160 x 160 x 70.7 mm3. We also found that our previously published correction technique reduced the largest error to 0.3 pixels (mu = 0.02 and sigma = 0.07 pixels).

  View details for Web of Science ID A1994MP54200005

  View details for PubMedID 8121267

• GREY VALUE CORRELATION TECHNIQUES USED FOR AUTOMATIC MATCHING OF CT AND MR BRAIN AND SPINE IMAGES 3rd Conference on Visualization in Biomedical Computing 1994 (VBC 94) VANDENELSEN, P. A., Pol, E. J., Sumanaweera, T. S., Hemler, P. F., Napel, S., Adler, J. R. SPIE - INT SOC OPTICAL ENGINEERING. 1994: 227–237

  View details for Web of Science ID A1994BB64H00024

• MOTION PLANNING IN STEREOTAXIC RADIOSURGERY IEEE TRANSACTIONS ON ROBOTICS AND AUTOMATION Schweikard, A., Adler, J. R., Latombe, J. C. 1993; 9 (6): 764-774

  View details for Web of Science ID A1993MY60300006

• STEREOTAXIC RADIOSURGICAL ABLATION - AN ALTERNATIVE TREATMENT FOR RECURRENT AND MULTIFOCAL HEMANGIOBLASTOMAS - A REPORT OF 4 CASES SURGICAL NEUROLOGY Page, K. A., WAYSON, K., Steinberg, G. K., Adler, J. R. 1993; 40 (5): 424-428

  Abstract

  Craniotomy and resection is usually a safe and effective treatment for hemangioblastoma. However, since the surgical removal of recurrent and multifocal tumors can be associated with greater risks, stereotaxic radiosurgery was used to ablate hemangioblastomas in four patients with von Hippel-Lindau disease. In two of these cases a symptomatic lesion was surgically resected just prior to radiosurgery. The 11 radiosurgically treated tumors (four patients) were spherical and varied in diameter from 0.75 to 2.0 cm with a mean of 1.25 cm. Dose ranged from 30 to 75 Gy with a mean of 35 Gy. After a mean clinical and radiologic follow-up of greater than 1 1/2 years, tumor size and/or cyst formation was controlled in all cases. Nevertheless, it was necessary to temporarily shunt a tumor cyst in one patient. In another case, aggressive treatment resulted in symptomatic radiation necrosis. Despite such potential problems we believe that radiosurgical tumor ablation is a reasonable alternative to craniotomy and/or radiation therapy in poor risk patients. This report is believed to be the first published description of the use of radiosurgery in the treatment of hemangioblastoma.

  View details for Web of Science ID A1993ME16400012

  View details for PubMedID 8211662

• MR SUSCEPTIBILITY MISREGISTRATION CORRECTION IEEE TRANSACTIONS ON MEDICAL IMAGING Sumanaweera, T. S., Glover, G. H., Binford, T. O., Adler, J. R. 1993; 12 (2): 251-259

  Abstract

  The authors present a new in vivo method to correct the nonlinear, object-shape-dependent and material-dependent spatial distortion in magnetic resonance (MR) images caused by magnetic susceptibility variations. This distortion across the air/tissue interface before and after the correction is quantified using a phantom. The results are compared to the distortion-free computed tomography (CT) images of the same phantom by fusing CT and MR images using fiducials, with a registration accuracy of better than a millimeter. The distortion at the bone/tissue boundary is negligible compared to the typical MRI (MR imaging) resolution of 1 mm, while that at the air/tissue boundary creates displacements of about 2 mm (for G(x) 3.13 mT/m). This is a significant value if MRI is to provide highly accurate geometric measurements, as in the case of target localization for stereotaxic surgery. The correction scheme provides MR images with accuracy similar to that of CT: 1 mm. A new method to estimate the magnetic susceptibility of materials from MR images is presented. The magnetic susceptibility of cortical bone is measured using a SQUID magnetometer, and is found to be -8.86 ppm (with respect to air), which is quite similar to that of tissue (-9 ppm).

  View details for Web of Science ID A1993LV99000012

  View details for PubMedID 18218412

• MOTION PLANNING IN STEREOTAXIC RADIOSURGERY 1993 IEEE INTERNATIONAL CONF ON ROBOTICS AND AUTOMATION Schweikard, A., Adler, J. R., Latombe, J. C. I E E E, COMPUTER SOC PRESS. 1993: 909–916

  View details for Web of Science ID A1993BY79J00139

• STEREOTAXIC RADIOSURGERY OF BRAIN METASTASES - THE INFLUENCE OF NUMBER OF LESIONS ON SURVIVAL JOSEPH, J., ADLER, COX, R. S., HANCOCK, S. L. PERGAMON-ELSEVIER SCIENCE LTD. 1993: 257–58

  View details for DOI 10.1016/0360-3016(93)90840-R

  View details for Web of Science ID A1993LV40400271

• CEREBRAL HEMICORTICOECTOMY FOR EPILEPSY JOURNAL OF NEUROSURGERY Winston, K. R., Welch, K., Adler, J. R., Erba, G. 1992; 77 (6): 889-895

  Abstract

  Hemicorticectomy resulted in total or near-total control of seizures in 10 of 11 children with chronic epilepsy. During a median follow-up period of 5.5 years, there have been no deaths or delayed complications. The surgical outcome after hemicorticectomy compares favorably with that of more extensive surgical procedures, yet is associated with significantly less risk. The technique for hemicorticectomy is described and illustrated.

  View details for Web of Science ID A1992JZ28200010

  View details for PubMedID 1432131

• TEMPORAL LOBECTOMY FOR COMPLEX PARTIAL SEIZURES THAT BEGAN IN CHILDHOOD SURGICAL NEUROLOGY Erba, G., Winston, K. R., Adler, J. R., Welch, K., Ziegler, R., Hornig, G. W. 1992; 38 (6): 424-432

  Abstract

  Forty-six consecutive patients who underwent surgery for intractable temporal lobe seizures originating in childhood are reported; invasive preoperative monitoring (e.g., depth electrodes and subdural arrays) was not used in the selection process. Our results, with respect to the control of seizures and improvement in behavior, are comparable to those of series in which invasive monitoring was used in the selection process. Eighty-five percent of the 46 patients (96% of the 28 operated after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced near total control of their seizures. Our results indicate that many patients can be selected successfully for temporal resection without exposure to the risk and expense of invasive presurgical procedures. A long duration of epilepsy prior to surgery in patients with neoplasia portended a less satisfactory outcome. Our results strengthen the argument for early operation in children with intractable epilepsy.

  View details for Web of Science ID A1992KF60300004

  View details for PubMedID 1298107

• RADIOSURGERY FOR PALLIATION OF BASE OF SKULL RECURRENCES FROM HEAD AND NECK CANCERS CANCER Kaplan, I. D., Adler, J. R., Hicks, W. L., Fee, W. E., Goffinet, D. R. 1992; 70 (7): 1980-1984

  Abstract

  Seven patients received stereotaxic radiosurgery for 10 lesions at the base of the skull (BOS) from recurrent head and neck malignant neoplasms.A radiation dose of 17.5-35.0 Gy was delivered as a single fraction. Follow-up ranged from 1 to 14 months.Nine lesions were symptomatic, and the symptoms improved in five and stabilized in four lesions. In addition, a significant radiographic response was observed in 4 of 10 recurrences. Cranial nerve signs developed in two patients, and an area of asymptomatic necrosis developed in one patient in the temporal lobe tip.From their brief experience, the authors conclude that stereotaxic radiosurgery may be a promising treatment in locally controlling recurrent head and neck cancers that involve the BOS.

  View details for Web of Science ID A1992JP69200027

  View details for PubMedID 1525775

• Stereotactic, angiography-guided clipping of a distal, mycotic intracranial aneurysm using the Cosman-Roberts-Wells system: technical note. Neurosurgery Steinberg, G. K., GUPPY, K. H., Adler, J. R., Silverberg, G. D. 1992; 30 (3): 408-411

  Abstract

  We describe the use of stereotactic, angiographic guidance for localization and clipping of a small, distal intracranial bacterial aneurysm. The technique uses the commercially available Suetens-Gybels-Vandermeulen angiographic localizer with the widely used Cosman-Roberts-Wells stereotactic system. This method is simple and easy to use and significantly decreased the operative time. It may be quite useful for surgically treating mycotic and other peripheral aneurysms.

  View details for PubMedID 1620306

• STEREOTAXIC RADIOSURGICAL TREATMENT OF BRAIN METASTASES JOURNAL OF NEUROSURGERY Adler, J. R., Cox, R. S., Kaplan, I., Martin, D. P. 1992; 76 (3): 444-449

  Abstract

  In a series of 33 patients with reasonably controlled primary cancers, stereotactic radiosurgery was used to treat 52 brain metastases. After a mean radiological follow-up time of 5.5 months, six lesions (12%) had stabilized in size, 26 (50%) were significantly reduced, and 15 (29%) had disappeared. One large melanoma metastasis progressed relentlessly despite treatment. Five lesions (9%) had decreased in size slightly before enlarging. In two of these lesions, biopsy revealed only necrosis. In almost all cases, treatment was associated with decreased peritumoral edema. However, a group of patients with large metastases and extensive prior brain irradiation has been identified in whom prolonged symptomatic cerebral edema poses a problem. It is concluded that radiosurgery is a viable alternative to surgical resection for some cases of brain metastasis.

  View details for Web of Science ID A1992HF27400009

  View details for PubMedID 1738025

• MR SUSCEPTIBILITY DISTORTION QUANTIFICATION AND CORRECTION FOR STEREOTAXY CONF ON BIOMEDICAL IMAGE PROCESSING AND THREE-DIMENSIONAL MICROSCOPY Sumanaweera, T. S., Glover, G. H., Binford, T. O., Adler, J. R. SPIE - INT SOC OPTICAL ENGINEERING. 1992: 30–43

  View details for Web of Science ID A1992BW09J00004

• STEREOTAXIC RADIOSURGERY FOR BRAIN METASTASES - THE IMPORTANCE OF ADJUANT WHOLE BRAIN IRRADIATION INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Fuller, B. G., Kaplan, I. D., Adler, J., Cox, R. S., Bagshaw, M. A. 1992; 23 (2): 413-418

  Abstract

  Stereotaxic radiosurgery delivered from a modified 4 MV linear accelerator was used to treat 47 brain metastases in 27 patients at Stanford. Response was assessed in 41 lesions. Histopathologies included adenocarcinoma (24 lesions), renal cell carcinoma (9 lesions), melanoma (6 lesions), and squamous cell carcinoma (2 lesions). Follow-up ranged from 1.0-16.5 months, with a median of 5.0 months. Radiographic local control was achieved in 88% of the lesions. Three patients developed enlarging contrast-enhancing lesions in the radiosurgical field; one of these was biopsied and revealed necrosis with no viable tumor. Adjuvant whole brain irradiation (10 patients) was associated with regional intracranial control in 80% of patients. This was statistically superior (p = 0.0007) to the regional intracranial control rate achieved when radiosurgery alone was employed (6 patients). Most patients reported resolution of their neurologic symptoms, and were able to discontinue dexamethasone without impairment of neurologic function.

  View details for Web of Science ID A1992HW22500023

  View details for PubMedID 1375218

• RESULTS OF SURGERY FOR EXTRATEMPORAL PARTIAL EPILEPSY THAT BEGAN IN CHILDHOOD ARCHIVES OF NEUROLOGY Adler, J., Erba, G., Winston, K. R., Welch, K., Lombroso, C. T. 1991; 48 (2): 133-140

  Abstract

  Thirty-five consecutive patients who underwent surgery for intractable extratemporal seizures originating in childhood are described. Candidates for surgery were selected on the basis of clinical criteria, neurodiagnostic imaging, and an electroencephalographic investigation that included the use of sphenoidal electrodes and long-term monitoring. Invasive preoperative monitoring was not used. Our results, with respect to the control of seizures and behavioral improvement, are comparable with series in which data from invasive recordings were used in the selection process. Sixty-three percent of the 35 patients (76.5% of those operated on after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced a reduction in their frequency of seizures by at least 75%. The favorable outcome in this group of patients strengthens the argument for early operation in children with intractable epilepsy, even when the seizure focus is outside the temporal lobe.

  View details for Web of Science ID A1991EX21400005

  View details for PubMedID 1899561

• INTRALESIONAL IMMUNOTHERAPY OF BRAIN-TUMORS WITH COMBINED CORYNEBACTERIUM-PARVUM AND RECOMBINANT INTERLEUKIN-2 IN MICE JOURNAL OF THE NATIONAL CANCER INSTITUTE CONLEY, F. K., Adler, J. R., Duncan, J. A., Kennedy, J. D., SUTTON, R. C. 1990; 82 (16): 1340-1344

  Abstract

  Clinical observations and experimental work suggested that inflammatory cells attracted to the brain exert a nonspecific antineoplastic effect. Intralesional treatment of implanted malignant murine brain tumors (KHT sarcomas) with killed Corynebacterium parvum produced an inflammatory cell infiltrate and increased survival in C3H mice relative to that in untreated control C3H mice. This antitumor effect was enhanced when recombinant interleukin-2 was sequentially added as a second intralesional immunomodifier. A high percentage of mice so treated were cured. Inflammatory cells in the brains of treated mice divided for 1-2 weeks, and metabolic activity of astrocytes increased. These findings form the basis for a recently initiated immunotherapy protocol in patients with recurrent glioblastoma multiforme.

  View details for Web of Science ID A1990DU14600005

  View details for PubMedID 2380991

• POSTERIOR-FOSSA STEREOTAXIC BIOPSY USING THE BROWN-ROBERTS-WELLS STEREOTAXIC SYSTEM - TECHNICAL NOTE JOURNAL OF NEUROSURGERY Guthrie, B. L., Steinberg, G. K., Adler, J. R. 1989; 70 (4): 649-652

  Abstract

  Stereotaxic biopsy has been shown to be a reliable means of diagnosing posterior fossa lesions. The authors describe a technique for infratentorial transcerebellar stereotaxic access to posterior fossa parenchymal lesions using the Brown-Roberts-Wells apparatus in its standard commercial configuration. The necessity for tissue diagnosis of these lesions is briefly discussed.

  View details for Web of Science ID A1989T886000025

  View details for PubMedID 2647921

• EPILEPSY SURGERY IN CHILDREN JOURNAL OF CHILD NEUROLOGY Green, R. C., Adler, J. R., Erba, G. 1988; 3 (3): 155-166

  Abstract

  Neurosurgical procedures of established value in the treatment of the medically intractable epilepsies include temporal lobectomy, extratemporal cortical excision, hemispherectomy, and corpus callosotomy. The clinical decision to consider surgery in children with epilepsy requires an understanding of the natural history of pediatric seizures, the constraints of the presurgical evaluation, and the relationship between surgical outcome and tissue pathology. This article presents an overview of the indications, risks, and benefits of epilepsy surgery in the pediatric population.

  View details for Web of Science ID A1988P388800002

  View details for PubMedID 3145299

• HYDROCEPHALUS AND INTRASPINAL TUMOR NEUROSURGERY ZAVALA, L. M., Adler, J. R., Greene, C. S., Winston, K. R. 1988; 22 (4): 751-754

  Abstract

  Hydrocephalus with spinal subarachnoid obstruction is rare, and its cause is obscure. Two such patients are presented. The pathophysiology is reviewed. Spinal absorptive pathways for cerebrospinal fluid are postulated to play a critical role in such cases.

  View details for Web of Science ID A1988M973100024

  View details for PubMedID 3374788

• THE UPTAKE BY CHOROID-PLEXUS AND PASSAGE INTO CSF OF I-125 PROLACTIN IN PRETERM RABBITS INTERNATIONAL SYMP ON PEPTIDES AND AMINO ACID TRANSPORT MECHANISMS IN THE CENTRAL NERVOUS SYSTEM Lorenzo, A. V., Winston, K. R., Adler, J. STOCKTON PRESS. 1988: 67–78

  View details for Web of Science ID A1988BQ64M00006

• MANAGEMENT AND PREVENTION OF NECROSIS OF THE SCALP AFTER EMBOLIZATION AND SURGERY FOR MENINGIOMA SURGICAL NEUROLOGY Adler, J. R., Upton, J., Wallman, J., Winston, K. R. 1986; 25 (4): 357-360

  Abstract

  Ischemic necrosis of the occipital scalp followed embolization and surgery for a large convexity meningioma in one of our patients. This complication was successfully managed by free tissue transfer. Suggestions for the prevention of this serious complication are presented.

  View details for Web of Science ID A1986A373700007

  View details for PubMedID 3952629

• CHOREA AS A MANIFESTATION OF EPIDURAL HEMATOMA - CASE-REPORT JOURNAL OF NEUROSURGERY Adler, J. R., Winston, K. R. 1984; 60 (4): 856-857

  Abstract

  A child with epidural hematoma presented with choreiform movements which promptly resolved following the evacuation of the hematoma.

  View details for Web of Science ID A1984SL13700031

  View details for PubMedID 6707758

• EVIDENCE OF PROLACTIN RECEPTORS IN THE CHOROID-PLEXUS AND A POSSIBLE ROLE IN WATER-BALANCE IN NEONATAL BRAIN ZEITSCHRIFT FUR KINDERCHIRURGIE-SURGERY IN INFANCY AND CHILDHOOD Lorenzo, A. V., Winston, K. R., Welch, K., Adler, J. R., Granholm, L. 1983; 38: 68-70

  Abstract

  Tissue dehydration, including that of the brain, is a natural part of maturation. In the newborn it is accompanied by an acute salt water diuresis which is particularly pronounced in the premature infant. The decrease in cranial volume and fall in intracranial pressure to subatmospheric levels observed in premature infants after birth suggests that the brain shares in this process. Since fluid homeostasis is normally under hormonal control, the inordinate loss of fluid in the prematurely born may be attributable to a hormonal imbalance. The possibility that prolactin, a proven osmoregulatory hormone in submammalian species but not in mammals and primates, may have an important role in this process is suggested by recent evidence that prolactin regulates tissue water in fetal and newborn animals. If this hormone assists in the regulation of water and electrolyte content of the brain during the perinatal period then prolactin receptors might be expected at blood-brain and blood-CSF barriers. Our study with preterm, term and adult rabbits indicates that prolactin receptors are present and in much higher concentrations in the choroid plexus than in other tissues examined. Specific binding of prolactin to receptors on tissues normally is observed to increase with age. Since binding to the choroid plexus decreased with age it would suggest that the effect of prolactin on choroid plexus function may be more important during the perinatal than later stages of development.

  View details for Web of Science ID A1983RX59300004

  View details for PubMedID 6326414