Immune niches in brain metastases contain TCF1+ stem-like T cells, are associated with disease control and are modulated by preoperative SRS.

The CD8+ T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1+ TCF1+ stem-like CD8+ T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS's impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8+ T cells at 3 days. However, CD8+ T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1+ stem-like population.

Prospective 5-Year Analysis of the United States Radiation Oncology Job Market Using the ASTRO Career Center Website.

PURPOSE: We provide 5-year results of prospectively collected radiation oncology (RO) job opportunities and a longitudinal assessment of RO graduate numbers within the United States. METHODS AND MATERIALS: Full-time domestic RO job opportunities were collected and categorized using the American Society for Radiation Oncology (ASTRO) Career Center from July 1, 2016 to June 30, 2021. A chi-square test was used to compare regional job availability by city size and position type. The corresponding number of graduating United States (US) RO residents (2017-2021) was collected. US census and Medicare database resources were used as comparators for population and workforce estimates. Pearson's correlation coefficients were used to examine changes in data over time and a 2-tailed t test was used to assess for statistical significance. RESULTS: Over the 5-year study period, 819 unique job offers were posted, compared with 935 RO graduates (0.88 total jobs-to-graduates ratio). Most jobs were nonacademic (57.6%), located in populated areas >1 million (57.1%; median: 1.57M), with the largest proportion of jobs seen in the South region (32.4%). One-third of academic jobs were located at satellites. Regional differences were seen between academic versus nonacademic job availability (P < .01), with the highest proportion of academic jobs seen in the Northeast (60.3%) and the lowest in the Midwest (34.5%). Differences between regions were also observed for jobs in areas >1 million versus ≤1 million (P < .01), with the most jobs in areas >1 million seen in the West (64.6%) and the least in the South (51.3%). Regional job availability over time did not differ by position type (academic vs nonacademic) or population area size (P = .11 and P = .27, respectively). Annual graduate numbers increased with time (P = .02), with the highest percentage of graduates trained in the South (30.8%). Regional distribution of jobs versus graduates significantly differed (P < .01) with the lowest jobs-to-graduates ratio observed in the Northeast (0.67) and highest ratio in the West (1.07). Regional RO workforce estimates based on the 4336 radiation oncologists who were Medicare providers in 2020 were compared with total jobs and graduates by region with no difference observed between the distributions of the workforce and jobs (P = .39), but comparisons between the workforce and graduates were proportionally different (P < .01). The number of total jobs (vs graduates) per 10 million population in the Northeast, South, Midwest, and West were 30.2 (45.1), 21.0 (22.7), 30.6 (33.4), and 22.6 (21.2), respectively. CONCLUSIONS: This multiyear quantitative assessment of the RO job market and graduates identified fewer job opportunities than graduates overall in most regions, most notably in the Northeast. Regional differences were seen between available job type (academic vs nonacademic) and population size (>1 million vs ≤1 million). The findings are worrisome for trainee oversupply and geographic maldistribution. The number and distribution of RO trainees and residency programs across the US should be evaluated to minimize job market imbalance for future graduates, promote workforce stability, and continue to meet the future societal needs of patients with cancer.

Quantitative Medical Physics National Job Data Distribution Analysis.

PURPOSE: The purpose of this study was to investigate the contemporary distribution of medical physics (MP) employment opportunities across the United States. METHODS AND MATERIALS: An annual record (2018-2019) of advertised full-time MP jobs was created using publicly available information from the American Association of Physicists in Medicine and Indeed websites. Listed jobs were categorized based on position name, work experience, job function, and geographic region. To account for regional population differences, a preponderance of employment opportunities per 10 million people was computed. Using Commission on Accreditation of Medical Physics Education Programs residency accreditation data, the nationwide locations of the MP training centers and the number of residency positions per annum were identified. A chi-square goodness-of-fit test was used for statistical analysis. RESULTS: A total of 441 unique MP jobs were identified nationwide per annum (2018-2019). The highest percentage of MP jobs was reported from the South region (33.6%), and the lowest (17.2%) was from the West. Analysis revealed that 148 jobs (33.6%) were academic and 293 (66.4%) were nonacademic. The South had the most academic jobs overall (31.8%), whereas the West had the fewest (13.5%). Regionally, the highest percentage of academic jobs (46.9%) was reported from the Northeast, whereas the West had the lowest percentage (26.3%). The analysis of academic versus nonacademic job comparison by regions showed statistically significant differences (P = .0133). The Midwest and the West regions, respectively, showed the highest (18.2) and lowest (10.24) number of jobs per unit population, measured in 10 million. CONCLUSIONS: To our knowledge, this is one of the first national quantitative job data analyses of MP job distributions. This study revealed the level of demand for qualified candidates in 2018 to 2019, showing an imbalance between academic and nonacademic positions across the regions of the United States. Moreover, the geographic distribution of job listings deviated significantly from expectation given the relative population of each region.

Leptomeningeal disease and neurologic death after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis.

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

The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma.

BACKGROUND: Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. METHODS: We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post-subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. RESULTS: A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. CONCLUSIONS: This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post-subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

Women's Representation in Leadership Positions in Academic Medical Oncology, Radiation Oncology, and Surgical Oncology Programs.

Importance: Women are underrepresented in medical leadership positions; however, representation of women among academic oncology leadership is unknown. Objectives: To evaluate representation of women overall and in leadership positions in academic medical oncology (MO), radiation oncology (RO), and surgical oncology (SO) programs and to examine the association of women leadership with overall faculty representation of women per program. Design, Setting, and Participants: In this cross-sectional study, MO, RO, and SO training program websites were queried from October 2018 through June 2019. All faculty from 265 of 273 accredited MO, RO, and SO training programs (97.1%) were included. Exposure: Gender. Main Outcomes and Measures: Observed proportions of women in leadership positions compared with the expected proportion of overall women faculty in MO, RO, and SO were assessed. Rates of representation of women across each MO, RO, and SO program's faculty based on the presence or absence of a woman in a leadership position were compared. Results: Of 6030 total faculty, only 2164 (35.9%) were women. Total representation of women among MO, RO, and SO faculty was 37.1% (1563 of 4215), 30.7% (389 of 1269), and 38.8% (212 of 546), respectively. Women composed only 21.7% (30 of 138), 11.7% (11 of 94), and 3.8% (1 of 26) of MO, RO, and SO chair positions, respectively. The observed proportion of women in chair positions was significantly lower than the expected proportion for MO, RO, and SO. In all, 47.9%, 33%, and 18.5% of MO, RO, and SO programs, respectively, had at least 1 woman in a leadership position (program director or chair). Programs with 1 or more women in a leadership position were associated with a higher mean (SD) percentage of women faculty than those without at least 1 woman leader in MO (40.7% [12.5%] vs 33.1% [11.0%]; P < .001) and RO (36.2% [13.3%] vs 23.4% [12.3%]; P < .001) but not SO (40.2% [15.4%] vs 31.4% [16.9%]; P = .29). Conclusions and Relevance: Gender disparity exists in academic MO, RO, and SO faculty, which is magnified at the chair level. Programs in MO and RO with a woman physician in a leadership position were associated with a higher percentage of women faculty, but this was not true for SO. These data will serve as a benchmark to monitor progress toward a more balanced workforce.

Dosimetric Factors Related to Radiation Necrosis After 5-Fraction Radiosurgery for Patients With Resected Brain Metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBMs. METHODS AND MATERIALS: From 2008 to 2016, 55 rBMs at a single institution that were treated postoperatively with 5-fraction linear accelerator-based SRS (25-35 Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included radiation therapy dose to normal brain, location and magnitude of hotspots, clinical target volume (CTV), and margin size. Hotspot location was stratified as within the tumor bed alone (CTV) or within the planning target volume (PTV) expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence. Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic. RESULTS: Median age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cm3, the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed that max hotspots with a hazard ratio of 3.28 (P = .045), hotspots within the PTV expansion margin with relative magnitudes of 105%, 110%, and 111%, and an absolute dose of 33.5 Gy predicted for RN (P = .029, P = .04, P = .038, and P = .0488, respectively), but hotspots within the CTV did not. CONCLUSIONS: To our knowledge, this is the first study that investigated dosimetric factors that predict for RN after 5-fraction hypofractionated SRS for rBM. Hotspot location and magnitude appear important for predicting RN risk, thus these parameters should be carefully considered during treatment planning.

A 15-Year Profile of U.S. Radiation Oncology Residency Growth by Geographic Region, Metropolitan Size, and Program Size.

PURPOSE: The size and growth of U.S. radiation oncology (RO) residency positions have important implications for the RO workforce. There are no data on residency growth by geographic region, major urban centers, and program size. We aim to fill this gap. METHODS AND MATERIALS: A database of all RO programs and positions from 2003 to 2018 was created using National Resident Matching Program data. Programs were categorized by U.S. Census Bureau geographic region, major metropolitan location (top 10 combined statistical area vs all other), and program size (small [≤6 trainees], medium [7-12], and large [>12 trainees]). Linear regression with interaction terms was used to determine the effect of region, major metropolitan location, and program size on RO program and position growth over time. RESULTS: There has been a 69% (54-91) and 82% (106-193) increase in the number of RO programs and annual positions from 2003 to 2018. Differences in program and position growth, respectively, were seen in each category. Growth in the Northeast (92% and 83%), South (81% and 113%), and West (125% and 130%) has outpaced the Midwest (17% and 33%). Growth in top 10 metropolitan areas (77% and 92%) is higher than in all other areas (63% and 73%). Growth in medium (68% and 80%) and large (175% and 153%) programs is greater than in smaller (36% and 33%) programs. CONCLUSIONS: There has been a major increase in the number of RO residency programs and positions over the past 15 years. Growth is occurring in every major category but there are differences in magnitude within each category. This information can inform future decisions about RO training programs in the United States.

Predictors of Lymph Node Involvement by Soft Tissue Sarcoma of the Trunk and Extremity: An Analysis of the National Cancer Database.

Background and Objectives Lymph node metastases (LNM) in soft tissue sarcoma (STS) of the trunk and extremity are rare but are associated with worse survival. Established risk factors for LNM in this group are based on small institutional retrospective reviews. This study identifies the risk factors associated with LNM in otherwise non-metastatic trunk/extremity STS patients using the National Cancer Database (NCDB) and sought out to delineate a high-risk group that may be considered for pathologic nodal evaluation. Methods The files of 10,731 patients with STS of the trunk/extremity without distant metastasis from 2004 - 2015 were evaluated. Exclusion criteria included neoadjuvant therapy and a lack of pathologic nodal evaluation. Univariate and multivariable logistic regression models were performed to evaluate variables associated with LNM. Results Of the total of 10,731 patients, 223 (2.1%) had LNM. On multivariable analysis, LNM was associated with Grade 3 tumors (odds ratio (OR) 15.6, 95% confidence interval (CI) 6.36 - 38.04, p < 0.001) and clear cell/angiosarcoma/rhabdomyosarcoma/epithelioid (CARE) histology (OR 4.72, 95% CI 3.35 - 6.66, p < 0.001), lymphovascular invasion (LVI) (OR 5.86, 95% CI 3.33 - 10.31, p < 0.001, and bone invasion (BI) (OR 2.73, 95% CI 1.32 - 5.61, p = 0.006). Patients with Grade 3 CARE tumors (n = 402) had an 11.9% risk of LNM vs. 1.7% of adults without all these characteristics (p < 0.001). Patients with Grade 3 CARE tumors and either LVI or BI (n = 36) had a 33.3% risk of LNM. Conclusions High-grade and CARE histology are associated with LNM in STS. Adult patients with both features have an overall 11.9% risk of LNM and may be considered for pathologic LN assessment, particularly with the presence of LVI or BI.

Does the addition of chemotherapy to neoadjuvant radiotherapy impact survival in high-risk extremity/trunk soft-tissue sarcoma?

BACKGROUND: The role of chemotherapy in extremity/trunk soft-tissue sarcoma (ET-STS) is controversial, even for patients at high risk for distant recurrence and death (those with high-grade tumors ≥5 cm in size). This study examines the impact of integrating chemotherapy with neoadjuvant radiotherapy (RT) on overall survival (OS) for patients with high-risk ET-STS. METHODS: The National Cancer Data Base was queried for adult patients with high-risk ET-STS who received neoadjuvant RT and limb salvage surgery between 2006 and 2014. Patients were stratified into RT and chemoradiotherapy (CRT) cohorts. OS for the RT and CRT cohorts was analyzed with the Kaplan-Meier method, log-rank tests, and Cox proportional hazards models. Propensity score matching (PSM) analysis was used to account for a potential treatment selection bias between the cohorts. RESULTS: A total of 884 patients were identified: 639 (72.3%) in the RT cohort and 245 (27.7%) in the CRT cohort. The unadjusted 5-year Kaplan-Meier OS rate was significantly higher in the CRT cohort: 72.0% versus 56.1% (P < .001). Neoadjuvant chemotherapy was associated with improved OS in univariate and multivariable analyses (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.41-0.78; P < .001). PSM identified 2 evenly matched cohorts of 212 patients each. The 5-year matched Kaplan-Meier OS rates were 69.8% and 55.4% for the CRT and RT cohorts, respectively (P = .002). The addition of neoadjuvant chemotherapy remained prognostic for OS on PSM (HR, 0.56; 95% CI, 0.39-0.83; P = .003). CONCLUSIONS: The addition of chemotherapy to neoadjuvant RT was associated with improved OS for patients with high-risk ET-STS. In the absence of randomized data evaluating CRT versus RT, these findings warrant further investigation.

Safety and Efficacy of Palbociclib and Radiation Therapy in Patients With Metastatic Breast Cancer: Initial Results of a Novel Combination.

PURPOSE: Palbociclib is a selective cyclin-dependent kinase 4/6 inhibitor approved for metastatic ER+/HER2- breast cancer. Preclinical evidence suggests a possible synergistic effect of palbociclib when combined with radiation therapy (RT); however, the toxicity of this pairing is unknown. We report preliminary results on the use of this combination. METHODS AND MATERIALS: Records of patients treated with palbociclib at our institution from 2015 to 2018 were retrospectively reviewed. Patients who received RT for symptomatic metastases concurrently or within 14 days of palbociclib were included. Local treatment effect was assessed by clinical examination and subsequent computed tomography/magnetic resonance imaging. Toxicity was graded based on Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 16 women received palliative RT in close temporal proximity to palbociclib administration. Four patients received palbociclib before RT (25.0%), 5 concurrently (31.3%), and 7 after RT (43.8%). The median interval from closest palbociclib use to RT was 5 days (range, 0-14). The following sites were irradiated in decreasing order of frequency: bone (11 axial skeleton [9 vertebra and 2 other]; 4 pelvis; 3 extremity), brain (4: 3 whole brain RT and 1 stereotactic radiosurgery), and mediastinum (1). The median and mean follow-up time is 14.7 and 17.6 months (range, 1.7-38.2). Pain relief was achieved in all patients. No radiographic local failure was noted in the 13 patients with evaluable follow-up imaging. Leukopenia, neutropenia, and thrombocytopenia were seen in 4 (25.0%), 5 (31.3%), and 1 (6.3%) patient before RT. After RT, 5 (31.3%), 1 (6.3%), and 3 (18.8%) patients were leukopenic, neutropenic, and thrombocytopenic, respectively. All but 2 (grade 2) hematologic toxicities were grade 1. No acute or late grade 2+ cutaneous, neurologic, or gastrointestinal toxicities were noted. Toxicity results did not differ based on disease site, palbociclib-RT temporal association, or irradiated site. CONCLUSIONS: The use of RT in patients receiving palbociclib resulted in minimal grade 2 and no grade 3+ toxicities. This preliminary work suggests that symptomatic patients receiving palbociclib may be safely irradiated.

Retrospective analysis of safety and efficacy of anti-PD-1 therapy and radiation therapy in advanced melanoma: A bi-institutional study.

BACKGROUND AND PURPOSE: Antibodies against programmed cell death protein 1 (PD-1) are standard treatments for advanced melanoma. Palliative radiation therapy (RT) is commonly administered for this disease. Safety and optimal timing for this combination for melanoma has not been established. MATERIALS AND METHODS: In this retrospective cohort study, records for melanoma patients who received anti-PD-1 therapy at Duke University or Emory University (1/1/2013-12/30/2015) were reviewed. Patients were categorized by receipt of RT and RT timing relative to anti-PD-1. RESULTS: 151 patients received anti-PD-1 therapy. Median follow-up was 12.9 months. Patients receiving RT (n = 85) had worse baseline prognostic factors than patients without RT (n = 66). One-year overall survival (OS) was lower for RT patients than patients without RT (66%, 95% CI: 55-77% vs 83%, 95% CI: 73-92%). One-year OS was 61% for patients receiving RT before anti-PD-1 (95% CI: 46-76%), 78% for RT during anti-PD-1 (95% CI: 60-95%), and 58% for RT after anti-PD-1 (95% CI: 26-89%). On Cox regression, OS for patients without RT did not differ significantly from patients receiving RT during anti-PD-1 (HR 1.07, 95% CI: 0.41-2.84) or RT before anti-PD-1 (HR 0.56, 95% CI: 0.21-1.45). RT and anti-PD-1 therapy administered within 6 weeks of each other was well tolerated. CONCLUSION: RT can be safely administered with anti-PD-1 therapy. Despite worse baseline prognostic characteristics for patients receiving RT, OS was similar for patients receiving concurrent RT with anti-PD-1 therapy compared to patients receiving anti-PD-1 therapy alone.

Defining an Intermediate-risk Group for Low-grade Glioma: A National Cancer Database Analysis.

BACKGROUND: RTOG 9802 identified a cohort of patients with age less than 40 years and undergoing gross total resection as having low-risk, low-grade glioma (LR-LGG). European Organization for Research and Treatment of Cancer studies have demonstrated additional prognostic features in this group. The aim of this study was to analyze clinical factors associated with overall survival (OS), identify a potentially higher risk group within LR-LGG, and investigate patterns of care for adjuvant therapy. MATERIALS AND METHODS: Patients with LR-LGG diagnosed between 2010 to 2013 were identified in the National Cancer Database. Kaplan-Meier method was used to analyze OS. Propensity score matching and multivariate analysis were utilized to adjust for differences in cohorts. RESULTS: A total of 1,032 patients with LR-LGG were identified. Histological breakdown was 42.0% astrocytoma, 33.2% oligodendroglioma, and 25.8% mixed. Median follow-up was 3.9 years; median pre-operative tumor size was 4.0 cm. Overall, 834 (80.8%) underwent observation and 198 (19.2%) received adjuvant therapy. Tumor size >5 cm predicted for receipt of adjuvant therapy on regression analyses (OR=2.02, p=0.001). On multivariate analysis, tumor size >5 cm (hazard ratio=1.95) and non-oligodendroglioma histology (hazard ratio=2.50) were associated with inferior OS (both p<0.05). For patients with both poor prognostic features (a subset we consider "intermediate-risk"), 5-year OS was 78.4%, compared to 94.1% for all other low-risk patients (p<0.001). After propensity score matching, the intermediate-risk group continued to be associated with worse 5-year OS: 80.5% vs. 94.0%, p=0.004. CONCLUSION: Due to inferior OS for patients with LR-LGG with >5 cm, non-oligodendroglioma tumors, we propose an 'intermediate-risk' clinical classification for this subset.

A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases.

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

Preoperative Vs Postoperative Radiosurgery For Resected Brain Metastases: A Review.

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

Hemorrhagic and Cystic Brain Metastases Are Associated With an Increased Risk of Leptomeningeal Dissemination After Surgical Resection and Adjuvant Stereotactic Radiosurgery.

BACKGROUND: Brain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection. OBJECTIVE: To investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD. METHODS: One hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method. RESULTS: Median imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, P = .015), cystic features (HR 2.34, P = .013), breast histology (HR 3.23, P = .016), and number of brain metastases >1 (HR 2.09, P = .032) were independently associated with increased risk of LMD. CONCLUSION: Hemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk.

The Impact of Graduates' Job Preferences on the Current Radiation Oncology Job Market.

PURPOSE: To examine the role of radiation oncology (RO) graduates' application patterns and personal preferences in current labor concerns. METHODS AND MATERIALS: An anonymous, voluntary survey was distributed to 665 domestic RO graduates from 2013 to 2017. Questions assessed graduates' regional (Northeast [NE]; Midwest [MW]; South [SO]; West [WT]) job type and population size preferences. Top regional choice was compared across other categorical and numerical variables using the χ2 test and analysis of variance, respectively. RESULTS: Complete responses were obtained from 299 (45.0% response rate) participants: 82 (27.4%), 74 (24.7%), 85 (28.4%), and 58 (19.4%) graduated from NE, MW, SO, and WT programs. The most to least commonly applied regions were SO (69.2%), MW (55.9%), and then NE/WT (55.2% each). The first and last regional choices were the WT (29.4%) and MW (15.7%), respectively. The most and least common application and top choice preferences were consistent in terms of city size: >500,000 (86.0% and 64.5%, respectively) and <100,001 (26.1% and 7.0%, respectively). The majority of applicants applied to both academic and nonacademic positions (60.9%), with top job type choice being equally split. The majority of respondents independently received a job offer in their preferred region (75.3%), city population size (72.6%) or job type (81.9%). Additionally, 52.5% received a job offer that included all three preferences. Those who underwent residency training (44.3% vs 62.0%-83.6%, P < .001) or medical schooling (50.7% vs 56.3%-75.6%, P < .001) or grew up in the MW (60.8% vs 70.0%-74.7%, P < .001) were least likely to choose this region as their top regional choice compared with other regions. CONCLUSIONS: The MW and jobs in smaller cities are less appealing to RO graduates, even if they receive training in the MW, which may contribute to current job market concerns. Nonetheless, the majority of respondents received a job offer in the region, population size, and job type of their top choice. Assessing prospective candidates' city size and geographic preferences and prioritizing applicants who are compatible with positions may help address potential job market discrepancies.

Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm.

OBJECTIVEPreoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS and may lower the risk of radiation necrosis (RN) and leptomeningeal disease (LMD) recurrence. The study goal was to report the efficacy and toxicity of preoperative SRS in an expanded patient cohort with longer follow-up period relative to prior reports.METHODSThe records for patients with brain metastases treated with preoperative SRS and planned resection were reviewed. Patients with classically radiosensitive tumors, planned adjuvant whole brain radiotherapy, or no cranial imaging at least 1 month after surgery were excluded. Preoperative SRS dose was based on lesion size and was reduced approximately 10-20% from standard dosing. Surgery generally followed within 48 hours.RESULTSThe study cohort consisted of 117 patients with 125 lesions treated with single-fraction preoperative SRS and planned resection. Of the 117 patients, 24 patients were enrolled in an initial prospective trial; the remaining 93 cases were consecutively treated patients who were retrospectively reviewed. Most patients had a single brain metastasis (70.1%); 42.7% had non-small cell lung cancer, 18.8% had breast cancer, 15.4% had melanoma, and 11.1% had renal cell carcinoma. Gross total resection was performed in 95.2% of lesions. The median time from SRS to surgery was 2 days, the median SRS dose was 15 Gy, and the median gross tumor volume was 8.3 cm3. Event cumulative incidence at 2 years was as follows: cavity local recurrence (LR), 25.1%; distant brain failure, 60.2%; LMD, 4.3%; and symptomatic RN, 4.8%. The median overall survival (OS) and 2-year OS rate were 17.2 months and 36.7%, respectively. Subtotal resection (STR, n = 6) was significantly associated with increased risk of cavity LR (hazard ratio [HR] 6.67, p = 0.008) and worsened OS (HR 2.63, p = 0.05) in multivariable analyses.CONCLUSIONSThis expanded and updated analysis confirms that single-fraction preoperative SRS confers excellent cavity local control with very low risk of RN or LMD. Preoperative SRS has several potential advantages compared to postoperative SRS, including reduced risk of RN due to smaller irradiated volume without need for cavity margin expansion and reduced risk of LMD due to sterilization of tumor cells prior to spillage at the time of surgery. Subtotal resection, though infrequent, is associated with significantly worse cavity LR and OS. Based on these results, a randomized trial of preoperative versus postoperative SRS is being designed.

Proton vs. Photon Radiation Therapy for Primary Gliomas: An Analysis of the National Cancer Data Base.

Background: To investigate the impact of proton radiotherapy (PBT) on overall survival (OS) and evaluate PBT usage trends for patients with gliomas in the National Cancer Data Base (NCDB). Methods: Patients with a diagnosis of World Health Organization (WHO) Grade I-IV glioma treated with definitive radiation therapy (RT) between the years of 2004-13 were identified. Patients were stratified based on WHO Grade and photon radiotherapy (XRT) vs. PBT. Univariate (UVA) and multivariable analysis (MVA) with OS were performed by Cox proportional hazards model and log-rank tests. Propensity score (PS) weighting was utilized to account for differences in patient characteristics and to minimize selection bias. Results: There were a total of 49,405 patients treated with XRT and 170 patients treated with PBT. Median follow-up time was 62.1 months. On MVA, the following factors were associated with receipt of PBT (all p < 0.05): WHO Grade I-II gliomas, treatment at an academic/research program, west geographic facility location, and surgical resection. After PS weighting, all patients treated with PBT were found to have superior median and 5 year survival than patients treated with XRT: 45.9 vs. 29.7 months (p = 0.009) and 46.1 vs. 35.5% (p = 0.0160), respectively. Conclusions: PBT is associated with improved OS compared to XRT for patients with gliomas. This finding warrants verification in the randomized trial setting in order to account for potential patient imbalances not adequately captured by the NCDB, such as tumor molecular characteristics and patient performance status. Importance of the Study: This is the first study that compares the outcomes of patients treated with photon based radiotherapy vs. proton based radiotherapy for patients with gliomas. In this retrospective analysis, the results demonstrate that proton therapy is associated with improved outcomes which support ongoing prospective, randomized clinical trials comparing the two modalities in patients with gliomas.

The importance of surgery in scalp angiosarcomas.

BACKGROUND: Scalp angiosarcomas (SA) are rare, representing <1% of soft tissue sarcomas. The optimal management of these tumors is unknown, with management based on small case series. We sought to assess the impact of different therapies on overall survival (OS), the practice patterns nationally, and identify factors associated with OS for non-metastatic scalp angiosarcomas. METHODS: A prospectively maintained database was used to identify non-metastatic scalp angiosarcomas who received some form of definitive therapy. Logistics regression, Kaplan-Meier, and Cox proportional-hazard models were utilized. RESULTS: A total of 589 patients met study entry criteria with a median follow-up of 4.2 years. The majority (482 patients, 81.8%) had upfront definitive resection and an additional 317 patients (65.8%) received postoperative radiation. Of the 107 patients who didn't have surgery, the majority (65 patients, 60.7%) received definitive radiation and 42 patients (39.3%) received radiation and chemotherapy. One-year and five-year survival estimates for patients not receiving definitive surgery were 68.0% (95%CI: 57.5-76.4) and 18.0% (95%CI: 10.2-27.5) respectively compared to 78.2% (95%CI: 74.0-81.9) and 34.1% (95%CI: 28.9-39.3) for patients receiving definitive surgery (p < 0.01). On multivariable analysis, age ≥65 years, tumor size ≥5 cm, and not receiving definitive surgery was associated with worse OS. CONCLUSIONS: The majority of patients with non-metastatic scalp angiosarcomas had upfront definitive surgery, with a subsequent improvement in OS, including when accounting for other patient and tumor factors. Postoperative radiation was frequently given. Our large series confirmed age and tumor size as prognostic factors for this rare disease.