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PURPOSE: Many cancer centers engage in multidisciplinary tumor board meetings to determine the optimal approach to complex cancer care. With the onset of the COVID-19 pandemic, many institutions changed the format of these meetings from in-person to virtual. The aim of this study was to determine if the change to a virtual meeting format had an impact on attendance and cases presented. METHODS: Tumor board records were analyzed to obtain attendance and case presentation information at a National Cancer Institute–designated Comprehensive Cancer Center. Twelve-month in-person tumor board data were compared with 12-month virtual tumor board data to assess for difference in attendance and case presentation patterns. RESULTS: Seven separate weekly tumor board meetings at the beginning of the study (breast, GI, gynecology, liver, lung, melanoma, and urology) were expanded to nine meetings on the virtual platform (+endocrine and pancreas). Overall attendance increased by 46% on the virtual platform compared with in-person meetings (4,030 virtual attendances v 2,753 in-person, P < .001). Increased attendance was present across all specialties on the virtual platform. In addition, the number of patient cases discussed increased from 2,127 in in-person meeting to 2,656 on the virtual platform (a 20% increase, P < .001). CONCLUSION: A significant increase was observed in overall tumor board attendance and in case presentations per meeting, requiring the expansion of additional weekly meetings. Furthermore, in a major cancer center with multiple community affiliates, virtual tumor boards may encourage increased participation from remote sites with the benefit of obtaining expert specialist advice as compared with geographically challenging in-person meetings.

Uveal melanoma (UM), the most frequently occurring non-cutaneous melanoma and most common primary intraocular malignancy in adults, arises from the melanocytes of the choroid in approximately 95% of cases. Prompt diagnosis and treatment is vital as primary tumor size is one of the key factors associated with survival. Despite recent advances in management, more than half of the patients develop metastatic disease which portends poor survival. Currently, treatment options for UM include local resection, enucleation, plaque brachytherapy, and/or particle beam radiotherapy (RT). Enucleation was initially the standard of care in the management of UM, but a shift towards eye-preserving therapeutic choices such as RT and local resection has been noted in recent decades. Plaque brachytherapy, a form of localized RT, is the most popular option and is now the preferred treatment modality for a majority of UM cases. In this review we discuss the etiopathogenesis, clinical presentation and diagnosis of UM and place a special emphasis on its therapeutic options. Furthermore, we review the current literature on UM management and propose a functional treatment algorithm for non-metastatic disease.

ObjectiveGamma knife (GK) staged stereotactic radiosurgery (Staged-SRS) has become an effective treatment option for large brain metastases (BMs); however, it has been challenging to evaluate the total dose because of tumor shrinkage between two staged sessions. This study aims to evaluate total biological effective dose (BED) in Staged-SRS, and to compare the BED with those in single-fraction SRS (SF-SRS) and hypo-fractionated SRS (HF-SRS).MethodsPatients treated with GK Staged-SRS at a single institution were retrospectively included. The dose delivered in two sessions of Staged-SRS was summed using the deformable image registration. Each patient was replanned for SF-SRS and HF-SRS. The total BEDs were computed using the linear-quadratic model. Tumor BED98% and brain V84Gy2, equivalent to V12Gy in SF-SRS, were compared between SF-SRS, HF-SRS, and Staged-SRS plans with the Wilcoxon test.ResultsTwelve patients with 24 BMs treated with GK Staged-SRS were identified. We observed significant differences (p < 0.05) in tumor BED98% but comparable brain V84Gy2 (p = 0.677) between the Staged-SRS and SF-SRS plans. No dosimetric advantages of Staged-SRS over HF-SRS were observed. Tumor BED98% in the HF-SRS plans were significantly higher than those in the Staged-SRS plans (p < 0.05). Despite the larger PTVs, brain V84Gy2 in the HF-SRS plans remained lower (p < 0.05).ConclusionWe presented an approach to calculate the composite BEDs delivered to both tumor and normal brain tissue in Staged-SRS. Compared to SF-SRS, Staged-SRS delivers a higher dose to tumor but maintains a comparable dose to normal brain tissue. Our results did not show any dosimetric advantages of Staged-SRS over HF-SRS.

ObjectivesThe purpose of this study is to independently compare the performance of the inverse planning algorithm utilized in Gamma Knife (GK) Lightning Treatment Planning System (TPS) to manual forward planning, between experienced and inexperienced users, for different types of targets.Materials and MethodsForty patients treated with GK stereotactic radiosurgery (SRS) for pituitary adenoma (PA), vestibular schwannoma (VS), post-operative brain metastases (pBM), and intact brain metastases (iBM) were randomly selected, ten for each site. Three inversely optimized plans were generated for each case by two experienced planners (OptExp1 and OptExp2) and a novice planner (OptNov) using GK Lightning TPS. For each treatment site, the Gradient Index (GI), the Paddick Conformity Index (PCI), the prescription percentage, the scaled beam-on time (sBOT), the number of shots used, and dosimetric metrics to OARs were compared first between the inversely optimized plans and the manually generated clinical plans, and then among the inversely optimized plans. Statistical analyses were performed using the Student’s t-test and the ANOVA followed by the post-hoc Tukey tests.ResultsThe GI for the inversely optimized plans significantly outperformed the clinical plans for all sites. PCIs were similar between the inversely optimized and clinical plans for PA and VS, but were significantly improved in the inversely optimized plans for iBM and pBM. There were no significant differences in the sBOT between the inversely optimized and clinical plans, except for the PA cases. No significant differences were observed in dosimetric metrics, except for lower brain V12Gy and PTV D98% in the inversely optimized plans for iBM. There were no noticeable differences in plan qualities among the inversely optimized plans created by the novice and experienced planners.ConclusionInverse planning in GK Lightning TPS produces GK SRS plans at least equivalent in plan quality and similar in sBOT compared to manual forward planning in this independent validation study. The automatic workflow of inversed planning ensures a consistent plan quality regardless of a planner’s experience.

PurposeIn radiotherapy, high radiation exposure to optic nerve (ON) can cause optic neuropathy or vision loss. In this study, we evaluated the pattern and extent of the ON movement using MRI, and investigated the potential dosimetric effect of this movement on radiotherapy.MethodsMRI was performed in multiple planes in 5 human subjects without optic pathway abnormalities to determine optic nerve motion in different scenarios. The subjects were requested to gaze toward five directions during MRI acquisitions, including neutral (straight forward), left/right (horizontal movement), and up/down (vertical movement). Subsequently, the measured displacement was applied to patients with peri-optic tumors to evaluate the potential dosimetric effect of this motion.ResultsThe motion of ON followed a nearly conical shape. By average, the anterior end of ONs moved with 10.8 ± 2.2 mm horizontally and 9.3 ± 0.8 mm vertically, while posterior end has negligible displacement. For patients who underwent stereotactic radiotherapy to a peri-optic tumors, the movement of ON in this measured range introduced non-negligible dosimetric effect.ConclusionThe range of motion of the anterior portions of the optic nerves is on the order of centimeters, which may need to be considered with extra attention during radiation therapy in treating peri-optic lesions.

PURPOSE: Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS: This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS: Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [P = .049] and 16.4% v 33.3% [P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue (P = .04), less difficulty with remembering things (P = .01), and less difficulty with speaking (P = .049) and using imputed data, less interference of neurologic symptoms in daily activities (P = .008) and fewer cognitive symptoms (P = .01). CONCLUSION: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

Metastatic melanoma is often accompanied by the development of brain metastases, at presentation or during the course of therapy. Local therapies such as surgery and radiation have been considered standard treatments for intracranial disease. However, the emergence of systemic therapies has been changing the treatment paradigm for the management of brain metastases. In patients with BRAF-mutated melanoma, combined BRAF and MEK inhibition has been found to elicit significant clinical responses. Patients who develop resistance to MAP kinase (MAPK) targeted therapy can achieve significant responses upon rechallenge. In this case, a 68-year-old woman with metastatic melanoma who had received multiple treatment courses including combination immunotherapy and combination MAPK-targeted therapy presented with a brainstem metastasis and demonstrated a complete response upon initiation of encorafenib and binimetinib, thereby obviating the need for stereotactic radiosurgery.

Objective Metastatic melanoma patients often receive palliative radiotherapy (RT) and immunotherapy (IT). However, the immunological interplay between RT dose-fractionation and IT is uncertain, and the optimal treatment strategy using RT and IT in metastatic melanoma remains unclear. Our main objective was to examine the effect of RT dose-fractionation on overall survival (OS). Methods Using the National Cancer Database (NCDB), we classified metastatic melanoma patients who received palliative RT into two dose-fractionation groups - conventionally fractionated RT (CFRT

Purpose: Strong mentorship has been shown to improve mentee productivity, clinical skills, medical knowledge, and career preparation. We conducted a survey to evaluate resident satisfaction with mentorship within their radiation oncology residency programs. Methods and Materials: In January 2019, 126 radiation oncology residents training at programs in the northeastern United States were asked to anonymously complete the validated Munich Evaluation of Mentoring Questionnaire (MEMeQ). Results of residents with a formal mentoring program were compared to those without a formal program. Results: Overall response rate was 42%(n = 53). Participants were 25% post-graduate year two (PGY-2), 21% PGY-3, 26% PGY-4, and 28% PGY-5. Only 38% of residents reported participation in a formal mentoring program, while 62% had no formal program, and 13% reported having no mentor at all. Residents participating in a formal mentoring program reported strikingly higher rates of overall satisfaction with mentoring compared to those who were not (90% vs. 9%, p < 0.001). Overall, 38% of residents were either satisfied/very satisfied with their mentoring experience, while 49% of residents were unsatisfied/very unsatisfied. Conclusion: Residents participating in a formal mentorship program are significantly more likely to be satisfied with their mentoring experience than those who are not. Our results suggest that radiation oncology residency programs should strongly consider implementing formal mentorship programs.

e21551 Background: Combined BRAF/MEK inhibition results in improved progression free and overall survival in BRAF mutated melanoma, but significant response is not universally observed. TERT promoter activating mutations often co-occur with BRAF mutations and have been associated with aggressive features and poorer prognosis. The TERT promotor inhibits apoptosis via a mechanism dependent upon BRAF mutant MAPK activation. Preclinical data in mouse models suggests that BRAF/TERT genetic duet melanomas are associated with improved response to BRAF/MEK inhibition as compared with BRAF mutant/TERT-WT melanomas. Methods: We performed a single center retrospective analysis of adults with melanoma with confirmed BRAF mutations +/- TERT promoter mutations. Responses and progression free survival in response to BRAF/MEK inhibition was assessed. Differences in RR and PFS were compared using Kaplan-Meier and Log-Rank. Results: 52 cases of BRAF/TERT genetic duet and BRAF mutated/TERT-WT melanomas were assessed. A total of 24 patients received BRAF/MEK inhibitors over the course of treatment meeting criteria for study inclusion; 9 (37.5%) BRAF/TERT genetic duet and 15 (62.5%) BRAF mutated/TERT-WT. BRAF V600E was present in 19/24 (79.2%) and V600K in 5/24 (20.8%). In the genetic duets, TERT -146C > T was present in 4/9 (44.4%), -124C > T in 2/9 (22.2%), -139_-138CC > TT in 2/9 (22.2%), and a SNV in 1/9 (11.1%). Mean age at diagnosis was 56 ± 13.5 years and 62.5% were male. ECOG PFS was 0-1 in 15/24 (62.5%), 2-3 in 6/24 (25%), and unreported in 3/24 (12.5%). Mean LDH at start of therapy was 391 (range 81-1664). At initial diagnosis 20.8% were Stage I, 25% Stage II, 37.5% Stage III, and 16.7% Stage IV. Two or more sites of disease were present in 10/24 (41.7%) and 2/24 (8.3%) had CNS metastases. BRAF/MEK directed therapy was first line in 6/24 (25%) of patients, others received prior immunotherapy. No significant differences between groups were observed in baseline demographics, disease state at diagnosis, or treatment history. In BRAF/TERT genetic duet melanomas CR was observed in 1/9 (11.1%), PR in 7/9 (77.8%), and NR in 1/9 (11.1%). In BRAF mutated/TERT-WT CR was observed in 3/15 (20%), PR in 11/15 (73.3%), and NR in 1/15 (6.7%). BRAF/TERT genetic duets were observed to initially have somewhat better PFS on first exposure to BRAF/MEK directed therapy but the PFS curves crossed at about 5 months with no significant difference observed overall (p = 0.40). Conclusions: This study is the first to report on outcomes of BRAF/MEK directed therapy in BRAF/TERT genetic duet vs BRAF mutated/TERT-WT melanomas in humans. While preclinical data from mouse models observed an improved response to BRAF/MEK inhibition in genetic duet tumors, no significant difference was observed. Our study is limited by small sample size. A multicenter analysis may be of interest to better understand the effects of BRAF inhibition in patients with BRAF/TERT genetic duet melanoma.

Purpose: Renal cell carcinoma (RCC) and melanoma have been considered `radioresistant' due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases. Materials and Methods: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors. Results: We identified 53 radioresistant brain metastases (28\% RCC and 72\% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 +/- 9.5 mL and 95.5\% +/- 2.9\%, respectively. The mean prescription dose was 20 +/- 4.9 Gy. Forty lesions (75\%) demonstrated a complete/partial response and 13 lesions (24\%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS. Conclusion: SRS is an effective management option with up to 75\% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.