Caressa Hui

All Publications

• Volumetric modulated arc therapy total body irradiation improves toxicity outcomes compared to 2D total body irradiation. Frontiers in oncology Hui, C., Simiele, E., Lozko, Y., Romero, I., Skinner, L., Binkley, M. S., Hoppe, R., Kovalchuk, N., Hiniker, S. M. 2024; 14: 1459287

  Abstract

  Volumetric modulated arc therapy (VMAT) total body irradiation (TBI) allows for greater organ sparing with improved target coverage compared to 2D-TBI. However, there is limited evidence of whether improved organ sparing translates to decreases in toxicities and how its toxicities compare to those of the 2D technique. We aimed to compare differences in toxicities among patients treated with TBI utilizing VMAT and 2D techniques.A matched-pair single-institution retrospective analysis of 200 patients treated with TBI from 2014 to 2023 was performed. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared using log-rank tests. Differences in characteristics and toxicities between the VMAT and 2D cohorts were compared using Fisher's exact test.Of the 200 patients analyzed, 100 underwent VMAT-TBI, and 100 underwent 2D-TBI. The median age for VMAT-TBI and 2D-TBI patients was 13.7 years and 16.2 years, respectively (p = 0.25). In each cohort, 53 patients were treated with myeloablative regimens (8-13.76 Gy), and 47 were treated with non-myeloablative regimens (2-4 Gy). For the entire VMAT-TBI cohort, lung Dmean, kidney Dmean, and lens Dmax were spared to 60.6% ± 5.0%, 71.0% ± 8.5%, and 90.1% ± 3.5% of prescription, respectively. For the non-myeloablative VMAT-TBI cohort, testis/ovary Dmax, brain, and thyroid Dmean were spared to 33.4% ± 7.3%, 75.4% ± 7.0%, and 76.1% ± 10.5%, respectively. For 2D-TBI, lungs were spared using partial-transmission lung blocks for myeloablative regimens. The VMAT-TBI cohort experienced significantly lower rates of any grade of pneumonitis (2% vs. 12%), nephrotoxicity (7% vs. 34%), nausea (68% vs. 81%), skin (16% vs. 35%), and graft versus host disease (GVHD) (42% vs. 62%) compared to 2D-TBI patients. For myeloablative regimen patients, rates of pneumonitis (0% vs. 17%) and nephrotoxicity (9% vs. 36%) were significantly lower with VMAT-TBI versus 2D-TBI (p < 0.01). Median follow-up was 14.3 months, and neither median OS nor PFS for the entire cohort was reached. In the VMAT versus 2D-TBI cohort, the 1-year OS was 86.0% versus 83.0% (p = 0.26), and the 1-year PFS was 86.6% and 80.0% (p = 0.36), respectively.Normal tissue sparing with VMAT-TBI compared to the 2D-TBI translated to significantly lower rates of pneumonitis, renal toxicity, nausea, skin toxicity, and GVHD in patients, while maintaining excellent disease control.

  View details for DOI 10.3389/fonc.2024.1459287

  View details for PubMedID 39351359

  View details for PubMedCentralID PMC11439880

• Safety of pelvic and abdominal radiation therapy for patients with inflammatory bowel disease: a dosimetric analysis of acute bowel toxicity. International journal of radiation oncology, biology, physics Hall, J. C., Hall, A. K., Lozko, Y., Hui, C., Baniel, C. C., Jackson, S., Vitzthum, L. K., Chang, D. T., Rahimy, E., Pollom, E. L. 2024

  Abstract

  OBJECTIVES: Inflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) due to the potential greater risk of RT-induced toxicities. This study aims to assess acute toxicity outcomes in patients with IBD treated with abdominal/pelvic RT.METHODS: After institutional review board approval, patients with IBD who received RT to the abdomen/pelvis were identified from an institutional research repository and their electronic medical records were reviewed. The IBD cohort was matched 1:1 with controls according to all of the following: radiotherapy, gender, disease site, age, and year of RT. Acute toxicity was defined as toxicity occurring within 3 months of RT. Primary outcomes were assessed via univariable logistic regression models and predicted probability of acute toxicity and acute gastrointestinal (GI) toxicity were plotted for the most significant covariates. IBD and control control cohorts were compared on demographic and toxicity variables using chi-square/Fisher's exact tests and Kruskal-Wallis tests where appropriate.RESULTS: We identified 62 patients with median age of 64 years (interquartile range [IQR] 54-70) who received RT from 2006-2022. Patients were treated with intensity-modulated RT (38; 61.3%), 3-dimensional conformal RT (12; 19.4%), and stereotactic body RT/brachytherapy (12; 19.4%). After RT, 28 (45.2%) and 23 (37.1%) patients experienced grade ≥2 acute (any) and acute GI toxicity, respectively. Higher overall RT dose and RT dose to small bowel were found to be signicantly associated with increased risk of grade ≥2 acute toxicities (OR=1.041 per unit Gy, 95% CI 1.005-1.084, p=0.034 and OR=1.046, 95% CI 1.018-1.082, p=0.003, respectively). Between IBD and control cohorts, there were no significant differences in grade ≥2 acute (any) and acute GI toxicities (p=0.710 and p=0.704, respectively).CONCLUSION: In patients with IBD treated with abdominal/pelvic RT for malignancy, RT was effective and well-tolerated. RT treatment planning should carefully consider the location(s) of IBD inflammation and dose to bowel structures, in particular, dose to small bowel.

  View details for DOI 10.1016/j.ijrobp.2024.09.005

  View details for PubMedID 39270827

• Cultural and social barriers to hope in gastrointestinal cancer patients. Journal of gastrointestinal oncology Qu, V., Hui, C., Fang, Z., Jackson, S., Vitzthum, L., Rahimy, E., Hall, J., Pollom, E. L. 2024; 15 (4): 1487-1496

  Abstract

  Hope is correlated with quality of life and overall survivorship among patients with cancer. We aimed to identify sociodemographic and clinical determinants of hope among patients with gastrointestinal (GI) cancer.Patients with GI cancer seen in radiation oncology between 10/2022 and 6/2023 were surveyed with the Adult Hope Scale (AHS) questionnaire, which assesses hope based on goal-setting and goal-striving beliefs. Linear regression and Pearson's/Spearman's correlation coefficients were used to evaluate associations between AHS scores and demographic or disease variables.One-hundred and forty-five (71.1% response rate) patients were included in the analysis. Most (75%) patients were symptomatic from disease, and Asian American and Pacific Islander (AAPI) patients accounted for 30.3% of our cohort. Identifying as AAPI or needing an interpreter for clinic visits was significantly associated with lower AHS scores, and more AAPI patients required interpreter assistance compared to non-AAPI patients (P=0.04). Being divorced, unemployed, or female was also linked to less hope. No other differences in hope were found.Sociodemographic rather than prognostic clinical factors were predictive of hope among patients with GI cancer. Interventions to contextualize psychosocial risk factors have the potential to improve quality of life and oncologic outcomes.

  View details for DOI 10.21037/jgo-23-938

  View details for PubMedID 39279929

  View details for PubMedCentralID PMC11399820

• Prognostic performance of FIGO 2023 endometrial carcinoma staging: a comparison to FIGO 2009 staging in the setting of known and unknown molecular classification. Histopathology Libert, D., Hammer, P. M., Hui, C., Kidd, E. A., Folkins, A. K., Longacre, T., Yang, E. J., Charu, V., Howitt, B. E. 2024

  Abstract

  The 2023 FIGO staging criteria for endometrial cancer (EC) introduced marked changes from the 2009 version. The full implication of these changes for patient diagnosis and treatment is unknown. We evaluate the differences in staging and prognostication between the two systems, with and without inclusion of molecular classification.We assigned (1) FIGO 2009, (2) 2023 molecular-agnostic and (3) 2023 molecular-informed stages to 404 fully staged and molecularly classified patients with EC. Disease-specific and progression/relapse-free survival were analysed via the Kaplan-Meier method and compared with log-rank testing; 118 of 252 (47%) FIGO 2009 stage I patients were upstaged based on histopathological findings alone. Stage I/II subgroup survival distribution analysis showed a worse prognosis in FIGO 2023 IIB and IIC patients. In the molecular-informed FIGO 2023 system, three of 15 (20%) POLE-mutated stage I/II cases were downstaged from FIGO 2009 and eight (53%) were downstaged from molecular-agnostic FIGO 2023. Fifty-one of 60 (85%) p53-abnormal tumours were upstaged from the FIGO 2009, whereas 13 of 60 (22%) were upstaged from the 2023 molecular-agnostic stage. Molecular classification improved prognostic stratification for both 2009 and 2023 FIGO systems.Downstaging based on POLE mutation more accurately represents patient outcomes. However, in the absence of known POLE status, applying molecular-agnostic FIGO 2023 criteria for stage I/II disease should be conducted with caution. For aggressive histotypes, additionally reporting FIGO 2009 stage should be considered. Upstaging based on substantial lymphovascular space invasion, aggressive histotype with any myometrial invasion and abnormal p53 improves prognostic discernment. Further subdivisions within stage I/II provide minimal additional prognostic information.

  View details for DOI 10.1111/his.15302

  View details for PubMedID 39209547

• Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases FromEGFRandALKOncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC). Journal of clinical oncology : official journal of the American Society of Clinical Oncology Pike, L. R., Miao, E., Boe, L. A., Patil, T., Imber, B. S., Myall, N. J., Pollom, E. L., Hui, C., Qu, V., Langston, J., Chiang, V., Grant, M., Goldberg, S. B., Palmer, J. D., Prasad, R. N., Wang, T. J., Lee, A., Shu, C. A., Chen, L. N., Thomas, N. J., Braunstein, S. E., Kavanagh, B. D., Camidge, D. R., Rusthoven, C. G. 2024: JCO2302668

  Abstract

  PURPOSE: Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.MATERIALS AND METHODS: Data on TKI-naive patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors.RESULTS: From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM ≥1 cm (P < .001) and neurologic symptoms (P < .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41 v 40 months, respectively; P = .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96]; P = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55]; P < .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival.CONCLUSION: The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR- and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.

  View details for DOI 10.1200/JCO.23.02668

  View details for PubMedID 39047224

• Tyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC). Miao, E., Pike, L. G., Boe, L. A., Patil, T., Myall, N., Hui, C., Pollom, E. L., Qu, V., Langston, J., Grant, M. J., Goldberg, S. B., Palmer, J., Prasad, R., Wang, T. C., Lee, A., Shu, C. A., Chen, L., Thomas, N. J., Camidge, D., Rusthoven, C. G., TURBO NSCLC LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557400381

• Opportunity in Complexity: Harnessing Molecular Biomarkers and Liquid Biopsies for Personalized Sarcoma Care. Seminars in radiation oncology Ewongwo, A., Hui, C., Moding, E. J. 2024; 34 (2): 195-206

  Abstract

  Due to their rarity and complexity, sarcomas represent a substantial therapeutic challenge. However, the incredible diversity within and across sarcoma subtypes presents an opportunity for personalized care to maximize efficacy and limit toxicity. A deeper understanding of the molecular alterations that drive sarcoma development and treatment response has paved the way for molecular biomarkers to shape sarcoma treatment. Genetic, transcriptomic, and protein biomarkers have become critical tools for diagnosis, prognostication, and treatment selection in patients with sarcomas. In the future, emerging biomarkers like circulating tumor DNA analysis offer the potential to improve early detection, monitoring response to treatment, and identifying mechanisms of resistance to personalize sarcoma treatment. Here, we review the current state of molecular biomarkers for sarcomas and highlight opportunities and challenges for the implementation of new technologies in the future.

  View details for DOI 10.1016/j.semradonc.2023.12.002

  View details for PubMedID 38508784

• Less than whole uterus irradiation for patients with locally advanced cervical cancer. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Hui, C., Ewongwo, A., Mendoza, M. G., Kozak, M. M., Jackson, S., Fu, J., Kidd, E. 2024: 110199

  Abstract

  Current consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation.We identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point.The median follow-up time was 65 months (range 3-352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3-9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups.Including less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity.

  View details for DOI 10.1016/j.radonc.2024.110199

  View details for PubMedID 38438017

• Development and clinical implementation of simple needle attachment post placement interstitial template (SNAPP-IT) enabling a shorter, more direct needle path while preserving tumor visualization. Brachytherapy Baniel, C. C., Hui, C., Franco, P. A., Niedermayr, T., Kidd, E. A. 2023

  Abstract

  PURPOSE: Historical gynecologic interstitial brachytherapy templates block direct tumor visualization during needle placement, presenting an opportunity for clinical innovation to develop a novel interstitial template allowing direct tumor visualization during needle insertion.METHODS AND MATERIALS: We designed and implemented a novel interstitial template, simple needle attachment post placement interstitial template (SNAPP-IT), that allowed direct visualization of the target vaginal tumor during interstitial needle placement while maintaining the ability to individually secure needles to the template, allow a vaginal cylinder, suture holes for securing to the perineum, MRI compatibility and sterilizable for repeat use. Procedure outcomes including procedure time, needle path lengths, and plan dosimetry were prospectively captured in a patient database.RESULTS: Forty gynecologic interstitial brachytherapy cases were recorded (20 SNAPP-IT, 20 traditional templates). Needle insertion depth was reduced using the SNAPP-IT in comparison with traditional interstitial templates (11.8 cm vs. 3.6 cm, p < 0.0001). The average CTV volume was 25.6 cc for SNAPP-IT and 20.7 cc for traditional; both methods averaged a similar number of needles (15.8, 15.6). Dosimetric constraints were similarly met in both treatment groups. Procedures performed using the SNAPP-IT were shorter compared with those performed with traditional interstitial devices (83.4 minutes vs. 100.7 minutes) and there were no post-operative infections in the SNAPP-IT group.CONCLUSIONS: Implementation of a novel gynecologic interstitial brachytherapy template (SNAPP-IT) reduced procedure times, allowed direct tumor visualization, and decreased needle insertion depth. SNAPP-IT provides a useful alternative approach for vaginal interstitial brachytherapy, may increase brachytherapist efficiency with complex procedures and potentially expands access to interstitial brachytherapy.

  View details for DOI 10.1016/j.brachy.2023.12.002

  View details for PubMedID 38160101

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

  Abstract

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

  View details for DOI 10.1016/j.ijrobp.2023.11.056

  View details for PubMedID 38056777

• Advancements without consensus: differing practice patterns highlight unanswered questions in the management of brain metastases from EGFR- and ALK-positive non-small cell lung cancer. Journal of thoracic disease Hui, C., Pollom, E. L., Li, G., Myall, N. J. 2023; 15 (11): 5877-5884

  View details for DOI 10.21037/jtd-23-1483

  View details for PubMedID 38090286

  View details for PubMedCentralID PMC10713290

• Patient Selection and Outcomes for Hypofractionated Accelerated Radiation and Concurrent Chemotherapy for Non-Small-Cell Lung Cancer. Clinical lung cancer Hui, C., Marquez, C., Lau, B., Das, M., Myall, N. J., Roy, M., Wakelee, H. A., Neal, J. W., Kovalchuk, N., Chin, A., Diehn, M., Loo, B. W., Xiang, M., Vitzthum, L. K. 2023

  Abstract

  Adoption of hypofractionated accelerated radiation therapy (HART) with concurrent chemotherapy has been limited by toxicity concerns. We aimed to describe outcomes of patients treated with HART and concurrent chemotherapy and to evaluate dosimetry to organs at risk to guide patient selection.We evaluated a retrospective cohort of NSCLC patients treated with concurrent chemotherapy with HART (>2.2 Gy per fraction) or standard fractionated radiation therapy (SFRT; 2-2.2 Gy fractions). Dosimetric parameters to key organs at risk were compared, and toxicity, patterns of recurrence and survival were calculated for the cohorts.Fifty-three patients treated with HART were compared with 100 patients treated with SFRT. Median dose per fraction for the HART cohort was 2.75 Gy (range 2.4-3 Gy). HART patients had significantly lower doses to the lung, heart, and esophagus due to patient selection. The HART group and had rates of grade 2+ pneumonitis (9.4 vs. 19%, P = .16) and grade 2+ esophagitis (20.8 vs. 45%, P < .01) that compared favorably to SFRT. Cumulative incidence of in-field recurrence trended lower in the HART cohort (7.6% vs. 23.1%, P = .058). Among the HART group, 88.7% (47/53) met the newly proposed lung constraints based on the degree of hypofractionation CONCLUSION: In select patients with favorable dosimetry to organs at risk, definitive HART with concurrent chemotherapy achieved excellent local control with low toxicity. These results are being used to inform a prospective study on the safety and efficacy of HART with concurrent chemotherapy for select NSCLC patients.

  View details for DOI 10.1016/j.cllc.2023.11.008

  View details for PubMedID 38065707

• Personalized Accelerated ChEmoRadiation (PACER) for Lung Cancer: Protocol for a Bayesian Optimal Phase I/II Trial. Clinical lung cancer Hui, C., Brown, E., Wong, S., Das, M., Wakelee, H., Neal, J., Ramchandran, K., Myall, N. J., Pham, D., Xing, L., Yang, Y., Kovalchuk, N., Yuan, Y., Lu, Y., Xiang, M., Chin, A., Diehn, M., Loo, B. W., Vitzthum, L. K. 2023

  Abstract

  Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs).Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping boundaries and evaluate the primary endpoint.PACER will evaluate the safety and feasibility of personalized accelerated chemoradiotherapy for lung cancer.

  View details for DOI 10.1016/j.cllc.2023.11.004

  View details for PubMedID 38040540

• Less than whole uterus irradiation for locally advanced cervical cancer maintains locoregional control and decreases radiation dose to bowel Kidd, E., Hui, C., Ewongwo, A., Mendoza, M. BMJ PUBLISHING GROUP. 2023: A104

  View details for DOI 10.1136/ijgc-2023-IGCS.175

  View details for Web of Science ID 001262421600367

• Advancements without consensus: differing practice patterns highlight unanswered questions in the management of brain metastases from<i> EGFR-</i> and<i> ALK</i>-positive non-small cell lung cancer JOURNAL OF THORACIC DISEASE Hui, C., Pollom, E. L., Li, G., Myall, N. J. 2023

  View details for DOI 10.21037/jtd-23-1483

  View details for Web of Science ID 001096720900001

• Outcomes and Imaging Analysis in Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy. Practical radiation oncology Hui, C., Baclay, R., Lau, B., von Eyben, R., Vitzthum, L., Pollom, E., Chang, D. T. 2023; 13 (2): e139-e148

  Abstract

  Although arterial phase enhancement is commonly used to evaluate treatment response for hepatocellular carcinoma, it may not accurately describe response for lesions treated with stereotactic body radiation therapy (SBRT). We aimed to describe the post-SBRT imaging findings to better inform the optimal timing of salvage therapy after SBRT.We retrospectively reviewed patients with hepatocellular carcinoma treated with SBRT from 2006 to 2021 at a single institution with available imaging showing lesions with characteristic arterial enhancement and portal venous washout. Patients were then stratified into 3 groups based on treatment: (1) concurrent SBRT and transarterial chemoembolization, (2) SBRT only, and (3) SBRT followed by early salvage therapy due to persistent enhancement. Overall survival was analyzed with the Kaplan-Meier method, and cumulative incidences were calculated with competing risk analysis.We included 82 lesions in 73 patients. The median follow-up time was 22.3 months (range, 2.2-88.1 months). The median time to overall survival was 43.7 months (95% confidence interval, 28.1-57.6 months) and median progression-free survival was 10.5 months (95% confidence interval, 7.2-14.0 months). There were 10 (12.2%) lesions that experienced local progression and there was no difference in rates of local progression between the 3 groups (P = .32). In the SBRT-only group, the median time to resolution of arterial enhancement and washout was 5.3 months (range, 1.6-23.7 months). At 3, 6, 9, and 12 months, 82%, 41%, 13%, and 8% of lesions, respectively, continued to show arterial hyperenhancement.Tumors treated with SBRT may continue to exhibit persistence of arterial hyperenhancement. Without an increase in size of enhancement, continued surveillance may be appropriate for these patients.

  View details for DOI 10.1016/j.prro.2022.08.012

  View details for PubMedID 36868725

• ASO Visual Abstract: Patterns of Recurrence after Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation. Annals of surgical oncology Hui, C., Ewongwo, A., Lau, B., Fisher, G., Delitto, D., Poultsides, G., Ho, Q. A., Rahimy, E., Pollom, E., Chang, D. T., Vitzthum, L. K. 2023

  View details for DOI 10.1245/s10434-023-14475-3

  View details for PubMedID 37875741

• ASO Author Reflections: A Role for Neoadjuvant Radiation in the Treatment of Locally Advanced Gastric Cancer? Annals of surgical oncology Hui, C., Vitzthum, L. K. 2023

  View details for DOI 10.1245/s10434-023-14403-5

  View details for PubMedID 37831276

  View details for PubMedCentralID 4517071

• Patterns of local recurrence and risk of skin recurrence in soft tissue sarcomas after surgical resection. Practical radiation oncology Ewongwo, A., Oladipo, E. D., Hui, C., Avedian, R. S., Steffner, R. J., Mohler, D. G., Kalbasi, A., Chin, A. L., Million, L., Hiniker, S. M., Moding, E. J. 2023

  Abstract

  Although there is a theoretical risk of skin seeding during surgical resection of soft tissues sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during RT. However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT.We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007-2021. For patients who developed LR, the depth was evaluated. Progression free survival (PFS) and overall survival (OS) were analyzed from time of first LR using Kaplan-Meier method. Cumulative incidence of distant metastasis (CIDM) was calculated with competing risk analysis from date of LR.Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, five patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had pre-operative RT, 53.3% had post operative RT, and bolus was used in 46.7%. Surgical margins were close (<1mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within RT field in 13 patients (86.7%). At 1 year after LR, PFS was 70.3%, OS was 81.7%, and CIDM was 5.9%.Skin recurrences were rare after surgical resection of STSs, and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

  View details for DOI 10.1016/j.prro.2023.09.006

  View details for PubMedID 37804883

• Patterns of Recurrence After Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation. Annals of surgical oncology Hui, C., Ewongwo, A., Lau, B., Fisher, G., Delitto, D., Poultsides, G., Ho, Q., Rahimy, E., Pollom, E., Chang, D. T., Vitzthum, L. K. 2023

  Abstract

  BACKGROUND: Improved treatment strategies are needed for patients with locally advanced gastric cancer with poor response to neoadjuvant chemotherapy. We aimed to describe patterns of failure for patients with no or partial response (NR, PR) to preoperative chemotherapy.PATIENTS AND METHODS: We analyzed patients with locally advanced gastric cancer treated from 2008 to 2022 with preoperative chemotherapy followed by surgery with D2 resection. We excluded patients who received radiation. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated. For patients with recurrent abdominal disease, hypothetical radiation clinical treatment volumes (CTV) were contoured on postoperative scans and compared with patterns of recurrence.RESULTS: A total of 60 patients were identified. The most used preoperative chemotherapy was FLOT (38.6%), followed by FOLFOX (30%) and ECF/ECX/EOX (23.3%). Four (6.7%), 40 (66.7%), and 9 patients (15%) had a complete pathologic response (CR), PR, and NR to neoadjuvant therapy, respectively. Among patients without a CR, 3-year overall and progression-free survival rates were 62.3% (95% CI 48-76.6%) and 51.3% (95% CI 36.9-65.7%), respectively. Three-year cumulative incidence of LRF and DM were 8.4% (95% CI 0.4-16.4%) and 41.0% (95% CI 26.3-55.4%), respectively. Absolute rates of patients having the first site of recurrence encompassed by a postoperative radiation CTV was 2.0% for patients without a CR and 0% for patients with NR.CONCLUSIONS: Patients with locally advanced gastric cancer with less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival.

  View details for DOI 10.1245/s10434-023-14350-1

  View details for PubMedID 37755563

• Does lymph node assessment change the prognostic significance of substantial LVSI and p53 status in endometrial endometrioid carcinoma? Gynecologic oncology Hui, C., Mendoza, M. G., von Eyben, R., Dorigo, O., Litkouhi, B., Renz, M., Karam, A., Hammer, P. M., Howitt, B. E., Kidd, E. 2023; 177: 150-156

  Abstract

  The PORTEC-2 update suggested that substantial lymphovascular space invasion (LVSI) and abnormal p53 expression (p53abnl) predict for poorer outcomes and that these patients should be treated with external beam radiation therapy (EBRT). We aim to determine if patients with these risk factors who undergo a lymph node (LN) assessment show similar outcomes.We retrospectively reviewed 126 patients with FIGO 2009 stage IA grade 3, stage IB grade 1-2, and stage IIIC (positive LN but no other stage II/III risk factors) endometrioid endometrial cancer who underwent LN assessment. Local (LR), regional recurrences (RR), and distant metastases were analyzed using competing risk methods, and overall survival (OS) was analyzed using Kaplan-Meier.Median follow-up time was 37.2 months. OS was significantly different between patients with and without p53abnl expression (16.7% versus 3.1% deceased), and between patients with and without LVSI (11.1% versus 1.5% deceased; p < 0.01 for both). The 2-year cumulative incidence of LR for patients with p53abnl versus wild type p53 and LVSI versus no LVSI was 11.1% (95% CI 0-25.6) versus 2.2% (95% CI 0-5.25; p = 0.04), and 11.4% (95% CI 2.0-20.9) versus 0%, respectively (p < 0.01). The 2-year cumulative RR in patients with LVSI versus no LVSI was 6.9% (95% CI 0-14.4) versus 0% (p = 0.05). No patients who completed pelvic RT experienced an in-field recurrence.Despite LN assessment, patients with high-intermediate risk early-stage or stage IIIC (with positive lymph nodes only but no other stage II or III risk factors) endometrial cancer with p53abnl expression and/or LVSI have worse outcomes. These patients may derive benefit from intensification with EBRT to improve local and pelvic control.

  View details for DOI 10.1016/j.ygyno.2023.09.001

  View details for PubMedID 37696217

• Management of Local-Regional Recurrence of Breast Cancer CURRENT BREAST CANCER REPORTS Hui, C., Dirbas, F. M., Horst, K. C. 2023

  View details for DOI 10.1007/s12609-023-00498-y

  View details for Web of Science ID 001029109100001

• Adjuvant radiation therapy in early-stage endometrial cancer with abnormal beta-catenin expression is associated with improved local control. Gynecologic oncology Hui, C., Mendoza, M. G., Snyder, J., Dorigo, O., Litkouhi, B., Renz, M., Karam, A., Devereaux, K., Howitt, B. E., Kidd, E. A. 2023; 174: 42-48

  Abstract

  Emerging data suggests that abnormal (nuclear) β-catenin expression in some settings is associated with poorer outcomes. Our study aimed to verify the significance of abnormal β-catenin expression in early-stage endometrial cancer patients and determine if adjuvant radiation therapy (RT) improves local control.We identified 213 patients with FIGO 2018 stage I-II endometrioid endometrial cancer who underwent surgery from 2009 to 2021 with β-catenin expression assessed. Vaginal, regional, and distant recurrences were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier.Median follow up was 53.2 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. For the entire cohort, abnormal β-catenin expression was significantly associated with vaginal recurrence and remained significant on multivariate analysis (p = 0.03). There were 114 patients in the no specific molecular profile (NSMP) subgroup, and abnormal β-catenin expression was present in 46.5%. In the NSMP subgroup, abnormal β-catenin expression was associated with increased rates of vaginal recurrence (p = 0.06). Abnormal β-catenin expression in the NSMP subgroup was significant on multivariate analysis for vaginal recurrence (p = 0.04). RT significantly decreased vaginal recurrences in the entire cohort in patients with abnormal β-catenin expression (0%) versus wild type expression (17.5%; p = 0.03). In the NSMP subgroup 0% of patients who received RT versus 20.9% of patients who did not receive RT experienced a vaginal recurrence (p = 0.03).Use of adjuvant RT for stage I-II NSMP endometrial cancer with abnormal β-catenin expression improved local control. RT should be considered in these patients to decrease risk of vaginal recurrences.

  View details for DOI 10.1016/j.ygyno.2023.04.018

  View details for PubMedID 37149904

• Effect of Radiation Schedule on Transportation-Related Carbon Emissions: A Case Study in Rectal Cancer. Advances in radiation oncology Frick, M. A., Baniel, C. C., Qu, V., Hui, C., Brown, E., Chang, D. T., Pollom, E. L. 2023; 8 (5): 101253

  Abstract

  The health care sector is a major contributor of worldwide greenhouse gas (GHG) emissions. Indirect emissions, including those associated with transportation, make up 82% of the US health care sector's environmental footprint. Radiation therapy (RT) treatment regimens present an opportunity for environmental health care-based stewardship owing to the high incidence of cancer diagnosis, significant utilization of RT, and myriad treatment days required for curative regimens. Because the use of short-course RT (SCRT) in the treatment of rectal cancer has demonstrated noninferior clinical outcomes compared with conventional, long-course RT (LCRT), we investigate the environmental and health equity-related outcomes.Patients treated with curative, preoperative RT for newly diagnosed rectal cancer at our institution between 2004 and 2022 and living in-state were included. Travel distance was estimated using patients' reported home address. Associated GHG emissions were calculated and reported in carbon dioxide equivalents (CO2e).Of 334 patients included, the total distance traveled for the treatment course was significantly greater in patients treated with LCRT versus SCRT (median, 1417 vs 319 miles; P < .001). Total CO2e emissions for those undergoing LCRT (n = 261) and SCRT (n = 73) were 665.3 kg CO2e and 149.9 kg CO2e, respectively, per treatment course (P < .001), with a net difference of 515.4 kg CO2e. Relatively, this suggests that LCRT is associated with 4.5 times greater GHG emissions from patient transportation.Using treatment of rectal cancer as proof-of-principle, we advocate for the inclusion of environmental considerations in the creation of climate-resilient oncologic RT practices, especially in the context of equivocal clinical outcomes between RT fractionation schedules.

  View details for DOI 10.1016/j.adro.2023.101253

  View details for PubMedID 37250284

  View details for PubMedCentralID PMC10209481

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

  Abstract

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

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

  View details for PubMedID 37016416

  View details for PubMedCentralID 7174761

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

  View details for Web of Science ID 000892639300120

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

  Abstract

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

  View details for DOI 10.7759/cureus.31838

  View details for PubMedID 36579260

  View details for PubMedCentralID PMC9788920

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

  Abstract

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

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

  View details for PubMedID 36227422

• Early Outcomes and Toxicity with Concurrent Chemotherapy and Hypofractionated Radiation Therapy in Patients with Non-Small Cell Lung Cancer Hui, C., Marquez, C., Lau, B., Von Eyben, R., Das, M., Myall, N., Roy, M., Chin, A., Diehn, M., Loo, B., Vitzthum, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S44

  View details for Web of Science ID 000847787800093

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

  View details for Web of Science ID 000847787800071

• Rectosigmoid Cancer-Rectal Cancer or Sigmoid Cancer? American journal of clinical oncology Hui, C., Baclay, R., Liu, K., Sandhu, N., Loo, P., von Eyben, R., Chen, C., Sheth, V., Vitzthum, L., Chang, D., Pollom, E. 2022

  Abstract

  OBJECTIVES: We aimed to determine the optimal treatment for patients with locally advanced rectosigmoid cancers, and to determine whether this can be guided by distance from anal verge (AV) and/or anatomic landmarks such as the sacral promontory and peritoneal reflection (PR).MATERIALS AND METHODS: We retrospectively reviewed patients with T3-T4 and/or node-positive rectosigmoid cancers who underwent surgery from 2006 to 2018 with available pelvic imaging. We included tumors at 9 to 20cm from the AV on either staging imaging, or colonoscopy. Patients were stratified into those who received neoadjuvant therapy, and those who underwent upfront surgery. Comparisons of characteristics were performed using chi2 test and Fischer exact test. Locoregional failure (LRF) and overall survival were compared using Cox regressions and Kaplan-Meier analysis.RESULTS: One hundred sixty-one patients were included. Ninety-seven patients had neoadjuvant therapy, and 64 patients had upfront surgery. Median follow-up time was 45.1 months. Patients who had neoadjuvant therapy had tumors that were higher cT stage (P<0.01) with more positive/close circumferential resection margins seen on imaging by radiologists (28.9% vs. 1.6%, P=0.015). The 2-year rate of LRF, distant metastases, or overall survival was not significantly different between the 2 groups. None of 15 patients with tumors below the PR treated with neoadjuvant therapy had LRF, but 1 (25%) of 4 patients with tumors below the PR treated with adjuvant therapy experienced LRF (P=0.05).CONCLUSIONS: Patients with tumors below the PR may benefit more from neoadjuvant therapy. The PR on imaging may be a reliable landmark in addition to the distance from the AV to determine the most appropriate treatment option.

  View details for DOI 10.1097/COC.0000000000000931

  View details for PubMedID 35848736

• Neoadjuvant therapy in the post-German rectal trial era: making sense in the absence of consensus. Practical radiation oncology Hui, C., Vitzthum, L. K., Chang, D. T., Pollom, E. L. 2022

  Abstract

  Trimodality therapy per the German Rectal trial has led to excellent locoregional outcomes for locally advanced rectal cancer. Recent efforts have shifted towards improving distant control and health-related quality of life in this disease. To this end, total neoadjuvant therapy has become an increasingly used approach where most, if not all, chemotherapy is delivered prior to surgery to improve compliance and to address micrometastases early. To avoid surgical morbidity, a "watch-and-wait" approach, in which total mesorectal excision is deferred, has also been studied for patients who achieve a clinical complete response after chemoradiation. These two concurrent treatment trends have raised many points of uncertainty in what used to be a relatively straightforward neoadjuvant treatment paradigm. We discuss here our approach to neoadjuvant therapy for locally advanced rectal cancer, based on the data we currently have and through shared decision-making with patients to help them select the treatment that best aligns with their preferences and values.

  View details for DOI 10.1016/j.prro.2022.06.010

  View details for PubMedID 35803535

• Volumetric modulated arc therapy total body irradiation in pediatric and adolescent/young adult patients undergoing stem cell transplantation: Early outcomes and toxicities. Pediatric blood & cancer Marquez, C., Hui, C., Simiele, E., Blomain, E., Oh, J., Bertaina, A., Klein, O., Shyr, D., Jiang, A., Hoppe, R. T., Kovalchuk, N., Hiniker, S. M. 2022: e29689

  Abstract

  INTRODUCTION: Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy total body irradiation (VMAT-TBI).METHODS: We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019 to 2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method.RESULTS: Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with nonmyeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs Dmean was 7.3 ± 0.3Gy for myeloablative regimens (range: 6.8-7.8). Kidneys were spared to average mean dose of 71.4 ± 4.8% of prescription dose. Gonadal sparing was achieved for patients treated for nonmalignant diseases to Dmean of 0.7 ± 0.1Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI.CONCLUSION: VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.

  View details for DOI 10.1002/pbc.29689

  View details for PubMedID 35373904

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

  Abstract

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

  View details for DOI 10.1089/thy.2021.0628

  View details for PubMedID 35229625

• The Stanford VMAT TBI Technique. Practical radiation oncology Kovalchuk, N., Simiele, E., Skinner, L., Yang, Y., Howell, N., Lewis, J., Hui, C., Blomain, E. S., Hoppe, R. T., Hiniker, S. M. 2022

  Abstract

  In this work, we describe the technical aspects of the XXX VMAT TBI technique, compare it to other VMAT TBI techniques, and share our initial experience.From September 2019 to August 2021, 35 patients were treated with VMAT TBI at our institution. Treatment planning was performed using in-house developed automated planning scripts. Organ sparing depended on the regimen: myeloablative (lungs, kidneys, and lenses); non-myeloablative with benign disease (lungs, kidneys, lenses, gonads, brain, and thyroid). Quality assurance was performed using EPID portal dosimetry and Mobius3D. Robustness was evaluated for the first ten patients by performing local and global isocenter shifts of 5 mm. Treatment was delivered using IGRT for every isocenter and every fraction. In-vivo measurements were performed on the matchline between the VMAT and AP/PA fields and on the testes for the first fraction.The lungs, lungs-1cm, and kidneys Dmean were consistently spared to 57.6±4.4%, 40.7±5.5%, and 70.0±9.9% of the prescription dose, respectively. Gonadal sparing (Dmean=0.69±0.13 Gy) was performed for all patients with benign disease. The average PTV D1cc was 120.7±6.4% for all patients. The average Gamma passing rate for the VMAT plans was 98.1±1.6% (criteria of 3%/2mm). Minimal differences were observed between Mobius3D- and EclipseAAA-calculated PTV Dmean (0.0±0.3%) and lungs Dmean (-2.5±1.2%). Robustness evaluation showed that the PTV Dmax and lungs Dmean are insensitive to small positioning deviations between the VMAT isocenters (1.1±2.4% and 1.2±1.0%, respectively). The average matchline dose measurement indicated patient setup was reproducible (96.1±4.5% relative to prescription dose). Treatment time, including patient setup and beam-on, was 47.5±9.5 min.The XXX VMAT TBI technique, from simulation to treatment delivery, was presented and compared to other VMAT TBI techniques. Together with publicly shared autoplanning scripts, our technique may provide the gateway for wider adaptation of this technology and the possibility of multi-institutional studies in the cooperative group setting.

  View details for DOI 10.1016/j.prro.2021.12.007

  View details for PubMedID 35182803

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

  View details for Web of Science ID 000701779700077

• Trimodality Versus Bimodality Therapy in Patients With Locally Advanced Esophageal Carcinoma: Commentary on the American Society of Clinical Oncology Practice Guidelines. Practical radiation oncology Vitzthum, L. K., Hui, C., Pollom, E. L., Chang, D. T. 2021

  Abstract

  In the recent guideline statement from the American Society of Clinical Oncology, experts reviewed relevant literature and provided treatment recommendations for multimodality treatment approaches. The guidelines recommend either preoperative concurrent neoadjuvant chemoradiotherapy (CRT) or perioperative chemotherapy for locally advanced adenocarcinoma and either preoperative CRT followed by esophagectomy or definitive CRT for squamous cell carcinoma. Whether radiation can be omitted in patients with adenocarcinoma or whether surgery can be omitted in patients with squamous cell carcinoma is a subject of ongoing debate and clinical trials.

  View details for DOI 10.1016/j.prro.2021.05.004

  View details for PubMedID 34353757

• Narrative review of immunotherapy and radiation therapy in elderly patients. Translational cancer research Chau, B., LaGuardia, J., Hui, C., Ye, L., Xing, Y., Massarelli, E., Amini, A. 2021; 10 (5): 2620-2631

  Abstract

  Cancer is primarily a disease of the elderly, but there is a disproportionate lack of data from clinical trials in this population. Oncologists tend to underdiagnose and undertreat geriatric patients with cancer, leading to poor survival outcomes. New therapies or therapeutic combinations such as immunotherapy and stereotactic body radiation therapy (SBRT) can be used in the elderly for better tumor control and survival, with fewer toxicities. The aim of this review is to describe the synergistic effects of immunotherapy and radiation therapy (RT) and to discuss the use of these therapies concurrently and/or sequentially in the elderly. To gain a fuller picture of their elderly patient's health, physicians may also consider incorporating a comprehensive geriatric assessment (CGA) to evaluate their functional capacity, cognition, physical and mental health, and social supports which we will discuss in this review. It is recommended that oncologists use geriatric assessments in their everyday practice to have better insight on their complex elderly patients, therefore providing them a higher quality of care. They should also be incorporated in clinical trials as a way to assess and include more elderly patients in the study. Ultimately, the elderly deserve to be treated with more than their chronological age in mind, and new combination therapies and use of a geriatric assessment can help achieve that.

  View details for DOI 10.21037/tcr-20-2637

  View details for PubMedID 35116575

  View details for PubMedCentralID PMC8799032

• Narrative review of immunotherapy and radiation therapy in elderly patients TRANSLATIONAL CANCER RESEARCH Chau, B., LaGuardia, J., Hui, C., Ye, L., Xing, Y., Massarelli, E., Amini, A. 2021; 10 (5): 2620-2631

  View details for DOI 10.21037/tcr-20-2637

  View details for Web of Science ID 000656696500058

• Radiation Therapy for Primary Cutaneous Gamma Delta Lymphoma Prior to Stem Cell Transplantation. Cancer investigation Wu, Y. F., Skinner, L., Lewis, J., Khodadoust, M. S., Kim, Y. H., Kwong, B. Y., Weng, W., Hoppe, R. T., Sodji, Q., Hui, C., Kastelowitz, N., Fernandez-Pol, S., Hiniker, S. M. 2021: 1–11

  Abstract

  We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the 4 extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

  View details for DOI 10.1080/07357907.2021.1919696

  View details for PubMedID 33899635

• Multimodality treatment including whole pleura radiation therapy for DICER1-associated pediatric pleuropulmonary blastoma. Pediatric blood & cancer Hui, C., Shin, D. H., Wakeling, A., Donaldson, S. S., Hazard, F. K., Rangaswami, A., Hiniker, S. M. 2021: e29004

  Abstract

  Limited data are available regarding radiation therapy in pediatric pleuropulmonary blastoma (PPB). We report the case of a 3-year-old girl with type II PPB successfully treated with trimodality therapy including multiagent chemotherapy, resection, and whole pleura radiation therapy. While longer follow-up is required to confirm ultimate local tumor control and long-term post-treatment sequelae, currently 3.5years following therapy, she is well, without recurrent disease or observable toxicity. The goal of this report is to add our experience to the literature regarding PPB, its management, and treatment, as prospective randomized controlled trials are not feasible due to the rarity of this disease.

  View details for DOI 10.1002/pbc.29004

  View details for PubMedID 33751747

• Improved Survival Outcomes in Medically Fit Patients With Early-Stage Non-Small-Cell Lung Cancer Undergoing Stereotactic Body Radiotherapy. Clinical lung cancer Liu, J., Hui, C., Ladbury, C., Waddington, T., Erhunmwunsee, L., Raz, D., Kim, J., Salgia, R., Chenery, S., Pearlstein, D., Schwer, A., Amini, A. 2021

  Abstract

  INTRODUCTION: Stereotactic body radiotherapy (SBRT) has been shown to result in excellent disease control rates for early-stage non-small-cell lung cancer (NSCLC). It remains unknown which patients would most benefit from SBRT in treating NSCLC.PATIENTS AND METHODS: We conducted a retrospective analysis of 346 patients treated with SBRT for early-stage NSCLC at 2 institutions (86 patients from City of Hope National Medical Center and 260 patients from The Newport Beach Radiosurgery Center/Hoag Hospital) from February 2010 to July 2019. The primary endpoint was overall survival (OS). The omnibus test of model coefficients was performed to study the associations between clinical factors and OS. Survival analyses were performed by the log-rank test and Cox proportional hazards regression.RESULTS: Under the univariate analysis, variables associated with a decreased likelihood of death included age< 65 years (P= .040) and being a surgical candidate (P= .010). Multivariate analysis found that surgical candidates still had a significantly decreased likelihood of death compared to nonsurgical candidates (Hazard ratio 0.360, 95% confidence interval 0.153-0.848, P= .019). Median OS was significantly increased for surgical candidates versus nonsurgical candidates (83 vs 53 months, P= .017). The local failure rate was 9.1%, the locoregional failure rate was 12.7%, and the distant failure rate was 10.7%.CONCLUSION: Patients who are deemed to be candidates for surgery have improved OS compared to those who are not when treated with SBRT. This raises the question of selection bias in trials comparing surgery with SBRT in NSCLC, as patients who are deemed to be surgical candidates and then go on to undergo surgery may have an inherent OS benefit.

  View details for DOI 10.1016/j.cllc.2021.01.003

  View details for PubMedID 33712362

• Overcoming Resistance to Immunotherapy in Head and Neck Cancer Using Radiation: A Review. Frontiers in oncology Hui, C., Chau, B., Gan, G., Stokes, W., Karam, S. D., Amini, A. 2021; 11: 592319

  Abstract

  Radiation therapy remains at the center of head and neck cancer treatment. With improvements in treatment delivery, radiation therapy has become an affective ablative modality for head and neck cancers. Immune checkpoint inhibitors are now also playing a more active role both in the locally advanced and metastatic setting. With improved systemic options, local noninvasive modalities including radiation therapy are playing a critical role in overcoming resistance in head and neck cancer. The aim of this review is to describe the role of radiation therapy in modulating the tumor microenvironment and how radiation dose, fractionation and treatment field can impact the immune system and potentially effect outcomes when combined with immunotherapy. The review will encompass several common scenarios where radiation is used to improve outcomes and overcome potential resistance that may develop with immunotherapy in head and neck squamous cell carcinoma (HNSCC), including upfront locally advanced disease receiving definitive radiation and recurrent disease undergoing re-irradiation. Lastly, we will review the potential toxicities of combined therapy and future directions of their role in the management of HNSCC.

  View details for DOI 10.3389/fonc.2021.592319

  View details for PubMedID 34277390

• Use of cardiac radiation therapy as bridging therapy to CAR-T for relapsed pediatric B-cell acute lymphoblastic leukemia. Pediatric blood & cancer Marquez, C. P., Montiel-Esparza, R., Hui, C., Schultz, L. M., Davis, K. L., Hoppe, R. T., Donaldson, S. S., Ramakrishna, S., Hiniker, S. M. 2020: e28870

  Abstract

  The use of radiotherapy as bridging therapy to chimeric antigen receptor T-cell therapy (CAR-T) in pre-B acute lymphoblastic leukemia (B-ALL) has been minimally explored. Here, we present a boy with B-ALL who relapsed after allogeneic bone marrow transplant with disseminated disease, including significant symptomatic cardiovascular and gastrointestinal (GI) involvement. The cardiac and GI leukemic infiltrates were successfully treated with bridging radiation therapy (BRT) prior to CAR-T infusion. Using this approach, he successfully tolerated CAR-T with no evidence of disease or sequelae on 3-month follow-up. This is the first reported case of safe and effective delivery of cardiac BRT in B-ALL.

  View details for DOI 10.1002/pbc.28870

  View details for PubMedID 33355997

• Radiologic Assessment of Groin Lymph Nodes in Pelvic Malignancies INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER Rudra, S., Fuser, D., DeWees, T. A., Wan, L., Gang, M., Hui, C. Y., Rao, Y. J., Siegel, B. A., Dehdashti, F., Mutch, D. G., Powell, M. A., Schwarz, J. K., Grigsby, P. W., Chen, D. L., Markovina, S. 2020; 30 (7): 947-953

  Abstract

  Metastatic involvement of groin nodes can alter radiation therapy planning for pelvic tumors. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) can identify nodal metastases; however, interpretation of PET/CT-positive nodes can be complicated by non-malignant processes. We evaluated quantitative metrics as methods to identify groin metastases in patients with pelvic tumors by comparison with standard subjective interpretive criteria, with pathology as the reference standard.We retrospectively identified patients with vulvar, vaginal, or anal cancers who underwent 18F-FDG PET/CT before pathologic evaluation of groin nodes between 2007 and 2017. Because patho-radiologic correlation was not possible for every node, one index node identified on imaging was selected for each groin. For each index node, standardized uptake value measurements, total lesion glycolysis, metabolic tumor volume, CT-based volume, and short and long axes were measured. Multivariate logistic regression was used to identify metrics predictive for pathologically positive groins and generate a probabilistic model. Area under the receiver-operating characteristic curves (AUCs) for the model were compared with clinical interpretation from the diagnostic report via a Wald's χ2 test.Of 55 patients identified for analysis, 75 groins had pathologic evaluation resulting in 75 index groin nodes for analysis with 35 groins pathologically positive for malignancy. Logistic regression identified mean standardized-uptake-value (50% threshold) and short-axis length as the most predictive imaging metrics for metastatic nodal involvement. The probabilistic model performed better at predicting pathologic involvement compared with standard clinical interpretation on analysis (AUC 0.91, 95% CI 0.84 to 0.97 vs 0.80, 95% CI 0.71 to 0.89; p<0.01).Accuracy of 18F-FDG PET/CT for detecting groin nodal metastases in patients with pelvic tumors may be improved with the use of quantitative metrics. Improving prediction of nodal metastases can aid with appropriate selection of patients for pathologic node evaluation and guide radiation volumes and doses.

  View details for DOI 10.1136/ijgc-2020-001363

  View details for Web of Science ID 000561760200008

  View details for PubMedID 32487684

• Impact of overall corticosteroid exposure during chemoradiotherapy on lymphopenia and survival of glioblastoma patients JOURNAL OF NEURO-ONCOLOGY Hui, C. Y., Rudra, S., Ma, S., Campian, J. L., Huang, J. 2019; 143 (1): 129-136

  Abstract

  Corticosteroids are commonly used to alleviate symptoms from cerebral vasogenic edema in glioblastoma (GBM) patients. This study evaluated the impact of overall corticosteroid exposure during chemoradiotherapy (CRT) on acute severe lymphopenia (ASL) and survival outcomes of GBM patients.GBM patients treated with CRT from 2007 to 2016 were retrospectively analyzed. Overall corticosteroid exposure was estimated as the average daily dexamethasone dose during 6 weeks of CRT. ASL was defined as grade 3 or higher lymphopenia within 3 months of starting CRT. ASL rates, overall survival (OS), and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Multivariable analysis (MVA) was performed using logistic and Cox regression to identify independent predictors of ASL and survival outcomes, respectively.Of the 319 eligible patients, the median daily dexamethasone use was 2 mg/day. The high-dose dexamethasone cohort (> 2 mg/day) had significantly higher ASL and worse OS than the low-dose dexamethasone cohort: 3-month ASL of 43.7% versus 19.8% (p < 0.003) and median OS of 12.6 months versus 17.9 months (p < 0.001), respectively. On MVA, higher dexamethasone use was independently associated with higher ASL and worse OS, but not worse PFS. A subset analysis of patients with gross-total resection found that higher dexamethasone use was significantly associated with ASL, but not OS.Increased corticosteroid use among GBM patients during CRT appears to be an independent risk factor for developing subsequent ASL. Its apparent association with worse OS may be influenced by other confounding factors and would need to be validated through prospective investigations.

  View details for DOI 10.1007/s11060-019-03146-7

  View details for Web of Science ID 000465615000015

  View details for PubMedID 30864102

• Treatment Patterns and Survival Outcomes for Patients with Small Cell Carcinoma of the Bladder EUROPEAN UROLOGY FOCUS Fischer-Valuck, B. W., Rao, Y., Henke, L. E., Rudra, S., Hui, C., Baumann, B. C., Gay, H. A., Michalski, J. M. 2018; 4 (6): 900-906

  Abstract

  Small cell carcinoma of the bladder (SCCaB) is a rare tumor without a standard treatment algorithm. Treatment patterns and survival outcomes from the National Cancer Database (NCDB) may provide insight into optimal treatment strategies.To investigate the relationship between overall survival (OS) and treatment strategy.This was an observational study of treatment-naïve patients who received treatment from 2004 to 2013. Patients with cT1-4aN0M0 SCCaB were identified from the NCDB, a hospital-based tumor registry that captures >70% of incident cancer cases in the USA.Treatment strategies included local therapy alone, chemotherapy (CT), radiation therapy (RT), chemoradiation therapy (CRT), radical cystectomy (RC), and RC plus chemotherapy (RC+C).OS was analyzed as a function of treatment modality adjusting for patient, demographic, and tumor-related factors. The Kaplan-Meier survival method, and the log-rank test and Cox regression were used for univariable and multivariable analyses.We identified 856 patients with median follow-up of 18.3 mo. The median OS for the entire cohort was 20.7 mo (95% confidence interval [CI] 18.3-23.2) and estimated 3-yr and 5-yr OS were 37.5% and 28.2%, respectively. The most common treatment modality was CT (225 patients; 26.3%) followed by CRT (203 patients; 23.7%) and RC+C (201 patients; 23.5%). The median OS was 18.4 mo (95% CI 15.2-21.5) for CT, 34.1 mo (95% CI 22.5-45.8) for CRT, and 32.4 mo (95% CI 20.8-44.1) for RC+C. OS did not significantly differ between CRT and RC+C (p=0.42). On multivariable analysis, the best OS was associated with CRT (hazard ratio [HR] 0.41, 95% CI 0.32-0.53; p<0.0001) and RC+C (HR 0.45, 95% CI 0.34-0.59; p<0.0001).RC+C and CRT are associated with better OS compared to monotherapy among patients with SCCaB.Small cell carcinoma of the bladder is a rare and highly aggressive cancer. According to National Cancer Database data, radical cystectomy plus chemotherapy and chemoradiation therapy are associated with better overall survival compared to monotherapy.

  View details for DOI 10.1016/j.euf.2017.09.001

  View details for Web of Science ID 000486148900015

  View details for PubMedID 28919521

• Radiologic Response and Disease Control of Recurrent Intracranial Meningiomas Treated With Reirradiation INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lin, A. J., Hui, C., Dahiya, S., Lu, H., Kim, A. H., Campian, J. L., Tsien, C., Zipfel, G. J., Rich, K. M., Chicoine, M., Huang, J. 2018; 102 (1): 194-203

  Abstract

  To evaluate the clinical outcomes of reirradiation of recurrent meningiomas and factors related to patient selection and treatment modality.Recurrent meningioma patients who failed prior stereotactic radiosurgery (SRS) or fractionated external beam radiation therapy (EBRT) received reirradiation using either SRS or EBRT. Complete response (CR), partial response (PR), and progression after reirradiation were evaluated using the MacDonald criteria. Local control (LC), progression-free survival (PFS), and overall survival (OS) after reirradiation were analyzed using the Kaplan-Meier method. Logistic and Cox regression analyses were performed to identify factors associated with reirradiation modality and PFS, respectively.Forty-three patients (14 grade 1/unknown, 29 grade 2/3) were reirradiated with SRS (67%) or EBRT (33%). Median time from initial SRS/EBRT to reirradiation was 60 months (range, 7.5-202); median tumor volume at the time of reirradiation was 4.8 cm3 (range, 0.14-64). After a median radiologic follow-up of 19.4 months, the response rate (CR + PR) was 8% for grade 1 and 20% for grade 2/3 meningiomas. After 2 years, LC was 78%, PFS was 63%, and OS was 80%. Larger tumor volume and prior SRS were associated with reirradiation using EBRT. Reirradiated grade 2/3 meningiomas had significantly worse PFS than grade 1 (2-year PFS: 50% vs 92%, respectively; P = .02) but not LC (P = .11) or OS (P = .39). On multivariable analysis, worse PFS was significantly associated with grade 2/3 histology (hazard ratio, 3.92; 95% confidence interval, 1.33-11.6) as well as worse Karnofsky Performance Scale score but not reirradiation dose, volume, and modality. Grades 3 to 4 radiation necrosis developed in 4 patients (10%).Reirradiation of recurrent meningiomas appears to be feasible with promising clinical outcomes and an acceptable toxicity profile.

  View details for DOI 10.1016/j.ijrobp.2018.05.011

  View details for Web of Science ID 000441076700030

  View details for PubMedID 29970312

• Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rudra, S., Hui, C., Rao, Y. J., Samson, P., Lin, A. J., Chang, X., Tsien, C., Fergus, S., Mullen, D., Yang, D., Thotala, D., Hallahan, D., Campian, J., Huang, J. 2018; 101 (1): 217-225

  Abstract

  To evaluate whether reduction in glioblastoma radiation treatment volume can reduce risk of acute severe lymphopenia (ASL).A total of 210 patients with supratentorial/nonmetastatic glioblastoma were treated with radiation therapy (RT) plus temozolomide from 2007 to 2016 and had laboratory data on total lymphocyte counts. Before 2015, 164 patients were treated with standard-field RT (SFRT), and limited-field RT (LFRT) was implemented thereafter for 46 patients to reduce treatment volume. Total lymphocyte counts were evaluated at baseline, during RT, and at approximately week 12 from initiating RT. Acute severe lymphopenia was defined as any total lymphocyte count < 500 cells/μL within 3 months (by week 12) of initiating RT. Multivariate analysis for overall survival (OS) was performed with Cox regression and with logistic regression for ASL. Propensity score matching was performed to adjust for variability between cohorts. Acute severe lymphopenia, progression-free survival (PFS), and OS were compared using the Kaplan-Meier method.Limited-field RT patients had higher gross tumor volume than SFRT patients yet lower brain dose-volume parameters, including volume receiving 25 Gy (V25 Gy: 41% vs 53%, respectively, P < .01). Total lymphocyte count at week 12 was significantly higher for LFRT than for SFRT (median: 1100 cells/μL vs 900 cells/μL, respectively, P = .02). On multivariate analysis, ASL was an independent predictor of OS, and brain V25 Gy was an independent predictor of ASL. The ASL rate at 3 months was 15.5% for LFRT and 33.8% for SFRT (P = .12). In a propensity-matched comparison of 45 pairs of LFRT and SFRT patients, PFS (median: 5.9 vs 6.2 months, respectively, P = .58) and OS (median: 16.2 vs 13.9 months, respectively, P = .69) were not significantly different.Limited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL.

  View details for DOI 10.1016/j.ijrobp.2018.01.069

  View details for Web of Science ID 000428886100028

  View details for PubMedID 29502931

• Impact of concurrent versus adjuvant chemotherapy on the severity and duration of lymphopenia in glioma patients treated with radiation therapy JOURNAL OF NEURO-ONCOLOGY Lin, A. J., Campian, J. L., Hui, C., Rudra, S., Rao, Y. J., Thotala, D., Hallahan, D., Huang, J. 2018; 136 (2): 403-411

  Abstract

  Prolonged severe lymphopenia has been shown to persist beyond a year in glioma patients after radiation therapy (RT) with concurrent and adjuvant chemotherapy. This study examines the differential impact of concurrent versus adjuvant chemotherapy on lymphopenia after RT. WHO grade II-III glioma patients who received RT with concurrent and/or adjuvant chemotherapy from 2007 to 2016 were retrospectively analyzed. Concurrent chemotherapy was temozolomide (TMZ), and adjuvant chemotherapy was either TMZ or procarbazine/lomustine/vincristine (PCV). Absolute lymphocyte count (ALC) was analyzed at baseline, 1.5, 3, 6, and 12 months after the start of RT. Univariable and multivariable logistic regression were used to identify the clinical variables in predicting acute or late lymphopenia. There were 151 patients with evaluable ALC: 91 received concurrent and adjuvant TMZ (CRT + ADJ), 32 received only concurrent TMZ (CRT), and 28 received only adjuvant TMZ or PCV (ADJ). There were 9 (10%) versus 6 (19%) versus 0 (0%) cases of grade 3 lymphopenia (ALC < 500/mm3) at 6 weeks and 4 (6%) versus 0 (0%) versus 3 (17%) cases at 12 months in CRT + ADJ, CRT and ADJ groups, respectively. On multivariable analyses, concurrent chemotherapy (odds ratio [OR] 72.3, p < 0.001), female sex (OR 10.8, p < 0.001), and older age (OR 1.06, p = 0.002) were the most significant predictors for any grade ≥ 1 lymphopenia (ALC < 1000/mm3) at 1.5 months. Older age (OR 1.08, p = 0.02) and duration of adjuvant chemotherapy (OR 1.19, p = 0.003) were significantly associated with grade ≥ 1 lymphopenia at 12 months. Thus, concurrent chemotherapy appears as the dominant contributor to the severity of acute lymphopenia after RT in WHO grade II-III glioma patients, and duration of adjuvant chemotherapy appears as the key factor to prolonged lymphopenia.

  View details for DOI 10.1007/s11060-017-2668-5

  View details for Web of Science ID 000422788000021

  View details for PubMedID 29143923

• Improved survival with definitive chemoradiation compared to definitive radiation alone in squamous cell carcinoma of the vulva: A review of the National Cancer Database GYNECOLOGIC ONCOLOGY Rao, Y., Chin, R., Hui, C., Mutch, D. G., Powell, M. A., Schwarz, J. K., Grigsby, P. W., Markovina, S. 2017; 146 (3): 572-579

  Abstract

  It is unclear whether definitive chemoradiation (CRT) results in improved overall survival compared to radiation therapy (RT) alone in patients with vulvar cancer who are not candidates for surgery. We compared these treatment strategies in the National Cancer Database (NCDB).We identified 1352 patients with pathologically-confirmed squamous cell carcinoma of the vulva treated with definitive RT (n=353) or definitive CRT (n=999) between 2003 and 2014 in the NCDB. Exclusion criteria were metastatic disease at diagnosis, RT dose <4000cGy, follow-up <6months, and surgical treatment. Overall survival was compared using Kaplan-Meier method with log-rank test. Cox proportional hazard modeling, propensity score matching, and subgroup analyses were performed.The median age overall was 66 (23-90) years. The CRT group was younger (p<0.001) and had more advanced FIGO staging (p<0.001) compared to the RT group. Median radiation dose was 5940 (4000-7920) cGy. The median follow-up for living patients was longer in the CRT group (45.2months [6.0-131.6]) than RT (34.4months [6.1-127.6]) (p=0.004). The 5-year overall survival was higher in the CRT group compared to RT (49.9% vs. 27.4%, p<0.001). On multivariate analysis, CRT was associated with a reduced hazard of death compared to RT (HR: 0.76 [0.63-0.91], p=0.003). The effect remained significant after propensity score matching (HR: 0.78 [0.63-0.97], p=0.023). On subgroup analysis, patients with FIGO stage I only had a trend towards improved survival with CRT (p=0.058).In the NCDB, definitive chemoradiation was associated with higher overall survival compared to radiation alone in patients with squamous cell carcinoma of the vulva who did not receive surgery. These findings suggest that concurrent chemoradiation may be beneficial for select patients in the definitive setting.

  View details for DOI 10.1016/j.ygyno.2017.06.022

  View details for Web of Science ID 000409158200021

  View details for PubMedID 28662775

• Which patients with inoperable vulvar cancer may benefit from brachytherapy in addition to external beam radiation? A Surveillance, Epidemiology, and End Results analysis BRACHYTHERAPY Rao, Y., Hui, C., Chundury, A., Schwarz, J. K., DeWees, T., Powell, M. A., Mutch, D. G., Grigsby, P. W. 2017; 16 (4): 831-840

  Abstract

  It is unknown whether brachytherapy after external beam radiation (EBRT + BT) results in improved outcomes compared with EBRT alone for patients with inoperable vulvar cancer. The purpose of this study was to compare survival outcomes for patients who received these treatment modalities.Data between 1973 and 2011 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients with Federation of International Gynecologists and Obstetricians stage I-IVA vulvar cancer treated with definitive EBRT + BT or EBRT alone were included. Patients with prior surgical resection were excluded. Disease-specific survival (DSS) and overall survival were compared using the Kaplan-Meier method and Cox proportional hazard models.A total of 649 patients were analyzed, of which 617 received EBRT alone and 32 received EBRT + BT. Median follow-up was 33 months in surviving patients. The use of brachytherapy declined from 16% of cases treated in 1973-1980 to 4% in 2001-2011 (p = 0.04). EBRT + BT vs. EBRT alone was not significantly associated with improved DSS (45% vs. 33% at 5 years) or overall survival (34% vs. 24% at 5 years) on univariate or multivariate analyses. On post hoc subgroup analyses, brachytherapy consolidation was associated with higher 5-year DSS in a composite subgroup that included patients with stage IVA disease, tumor >4 cm, or node-positive disease (52% vs. 27%, p = 0.02).Utilization of BT consolidation with EBRT for vulvar cancer is declining in the United States. EBRT + BT is not associated with improved survival compared with EBRT alone in the overall group of patients. Certain subgroups of patients might benefit from brachytherapy, but this hypothesis requires validation in future studies.

  View details for DOI 10.1016/j.brachy.2017.03.012

  View details for Web of Science ID 000407188700022

  View details for PubMedID 28533162

• Survival outcomes in elderly patients with muscle invasive bladder cancer: An analysis of the National Cancer Database. Fischer-Valuck, B., Rao, Y., Rudra, S., Hui, C., Baumann, B., Gay, H., Michalski, J. M. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.4538

  View details for Web of Science ID 000411931702038

• Association of post-treatment positron emission tomography with locoregional control and survival after radiation therapy for squamous cell carcinoma of the vulva RADIOTHERAPY AND ONCOLOGY Rao, Y., Hassanzadeh, C., Chundury, A., Hui, C., Siegel, B. A., Dehdashti, F., DeWees, T., Mullen, D., Powell, M., Mutch, D., Schwarz, J., Grigsby, P. 2017; 122 (3): 445-451

  Abstract

  The aim of this study was to investigate the use of post-treatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for vulvar cancer and compare metabolic response to clinical outcomes.This retrospective study included 21 patients with vulvar squamous cell carcinoma treated with curative-intent radiation between 2007 and 2015. All patients received intensity-modulated radiation treatment (IMRT), a pre-treatment FDG/PET-CT, and a post-treatment FDG-PET/CT performed at a median time of 3months post-IMRT.Median follow-up time was 28months. Post-treatment FDG-PET/CT demonstrated no evidence of disease (NED) in 12 patients and residual or progressive disease (PD) in 9. FDG-PET/CT response significantly correlated with biopsy-proven locoregional failure (p=0.02) and was the only significant factor associated with overall survival (OS) (p=0.049). Patients with NED on FDG-PET had a 2-year locoregional control (LRC) of 89% versus 25% for those with PD (p<0.01). Patients with NED on FDG-PET/CT had a 2-year OS of 100% versus 42% for those with PD (p=0.02). FDG-PET/CT evaluation had a sensitivity of 100% and a specificity of 71% for detecting pathologically proven residual disease in patients receiving neoadjuvant or definitive radiation.In this single-institution study of women with vulvar cancer, post-treatment response on FDG-PET/CT was associated with LRC and OS.

  View details for DOI 10.1016/j.radonc.2016.12.019

  View details for Web of Science ID 000397691500019

  View details for PubMedID 28063696