Search

Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly.A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA.Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P.01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies.Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.

Purpose/objective(s) Relapsed or refractory central nervous system lymphoma (CNSL) after high-dose methotrexate-based therapy is a challenging clinical entity with limited treatment options. Salvage systemic therapy and whole brain radiation therapy (WBRT) are commonly employed but are associated with significant toxicity and poor outcomes. Prior studies have shown that primary CNSLs frequently exhibit increased expression of PD-L1, and immune checkpoint inhibitor (ICI) therapy may be active in this setting. We assessed the safety and efficacy of concurrent ICI therapy and hypo-fractionated stereotactic radiation therapy (SRT) in patients with relapsed or refractory CNSL. Materials/methods We retrospectively analyzed the records of patients with relapsed or refractory CNSL treated with SRT + ICI at our institution from 2017 to 2020. ICI therapy included pembrolizumab 200 mg IV q3weeks or nivolumab 3 mg/mg IV q2weeks. Linac-based SRT was delivered in 5 daily fractions of 5 Gy. CTVs included all grossly enhancing disease on T1 weighted post-contrast MR scans, with 3 mm uniform PTV expansions. Patients were followed for symptomatic and radiographic response. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier analysis. Results Seven consecutive patients with relapsed or recurrent CNSL were analyzed: 6 with primary CNSL, 1 with secondary CNSL. Patients presented at a median age of 72.2 years (range: 40.9 - 89.9) after a median of 2 prior courses of systemic therapy. Five patients had a solitary intracranial lesion and 2 had multiple lesions. None had active extracranial disease. Median pre-SRT Karnofsky Performance Status (KPS) was 60 (range 50 - 90). All 7 patients completed SRT and received concurrent and adjuvant ICI therapy. Median follow-up after completion of SRT was 9.1 months. Acute toxicities of SRT and ICI therapy were minimal, including fatigue (3 patients), diarrhea (2), and adrenal insufficiency requiring oral steroids (1). Five patients (71.4%) achieved symptomatic improvement after SRT including 2 patients (28.5%) with a clinical complete response (CR). Median post-SRT KPS was 70 (range: 60 - 100). Six patients had follow-up imaging, and all had an objective response including 3 (50%) with a radiographic CR. The median time to best radiographic response was 2.0 months (range 0.3 - 3.7 months), and all treated lesions remained controlled on all subsequent imaging. Three patients (42.9%) experienced out-of-field intracranial recurrence. Median PFS was 7.7 months (95% CI: 4.0 - 11.4 months) and median OS was 12.6 months (95% CI: 7.5 - 12.7 months) post-SRT. Conclusion Among patients with relapsed or refractory CNSL, SRT + ICI appears to be well tolerated and offers excellent symptomatic and radiographic local control. Further studies are needed to identify appropriate candidates for salvage SRT + ICI, and to evaluate the clinical efficacy and neurocognitive impact of this approach.

Purpose/Objective(s) Medical students underrepresented in medicine (UIM) are less likely to attend medical schools with associated radiation oncology (RO) programs. In response, the Radiation oncology Intensive Shadowing Experience (RISE) was created to proactively address inequities in exposure to RO for UIM. This analysis describes the experiences of participating mentors. We hypothesize that RISE will have an overall positive impact on participating physician mentors. Materials/Methods RISE was developed as a one-week virtual opportunity for UIM senior medical students, interested in RO, attending US or US-affiliated medical schools. Participating medical students were matched with 1-2 RO attendings, a senior resident, a physicist, and a dosimetrist. Mentors were provided with course objectives and a detailed schedule for the week. Mentors completed a post-program survey. Statistical analyses were performed using Fisher's exact test and Mann–Whitney U test. Free text responses provided additional descriptive data. Results Forty-three mentors participated in RISE across two academic medical centers from July-October 2020. Survey response rate was 93% (40/43); 14 attendings, 12 residents, 9 physicists and 5 dosimetrists. Mentors self-identified as White (55%), Asian (34%), Multiracial (5%), Black or African American (3%), and Hispanic/Latino (3%). The majority of attendings and residents found that the goals and objectives were clearly stated, interactions with students were meaningful, and they would recommend the experience to other colleagues (Table 1). Attendings reported a median of 6 hours [interquartile range (IQR) 5,8 hours] on RISE activities per week while residents reported 10 hours [IQR 9,13.5 hours] (P = 0.01). All attendings (100%) and 83% of residents agreed the time commitment was appropriate. Qualitative data revealed themes including positive mentor-mentee connections, improvement in student RO knowledge, positive perception of mentee enthusiasm and engagement, and a sense of personal fulfillment from participation. Conclusion RISE mentors reported a positive and fulfilling experience with the program, and manageable time commitments. Time commitment for resident mentors may need to be improved to ensure sustainability. Future work is merited to determine the long-term impact on both mentors and mentees.

PURPOSE/OBJECTIVE(S) Leptomeningeal disease (LMD) is a devastating diagnosis with limited treatment options and poor prognosis. With recent advances in treatment, women with breast cancer (BC) are living longer and the incidence of LMD in this population is increasing. There remains little data regarding the prognosis and optimal treatment of these patients. As such, we conducted a multi-institutional retrospective review of women with BC LMD and analyzed outcomes based on prognostic factors and treatments. MATERIALS/METHODS We analyzed the records of women diagnosed with BC LMD via MRIs of their brain and/or spine between 2000 and 2020 at two academic medical centers. Demographic and clinical characteristics were abstracted from electronic medical records and an in-depth radiographic review was performed by a neuro-radiologist for each case. Univariate and multivariate Cox proportional-hazards models were generated to identify factors associated with prolonged survival. Collection and analysis of the data was approved by institutional IRB. RESULTS We identified 227 women with BC LMD. Prior to developing LMD, most women initially presented with Stage I-III BC (62.1%) with ductal histology (67.0%) and biological subtypes including ER-positive/HER2-negative (56.8%), HER2-positive (17.6%), and triple-negative (22.0%). LMD was first diagnosed a median of 4.6 years (range: 0 to 34.1 years) after the initial diagnosis of BC, and the median age at LMD diagnosis was 54.6 years (range: 29.4 to 84.5 years). At time of LMD diagnosis, 146 (64.3%) women presented with a Karnofsky Performance Status (KPS) ≥ 70, 90 (39.6%) had a preceding parenchymal brain metastasis, and 23 (10.1%) had LMD as their only site of metastatic disease. Radiographically, classical LMD (61.7%) was observed more frequently than nodular-only LMD (13.2%). Brain-only LMD was present in 55.1% of patients, spine-only in 6.1% of patients, and both brain and spine in 38.8% of patients. Median survival from the time of LMD diagnosis was 4.5 months (95% CI: 3.4-7.8). Pre-treatment clinical factors associated with improved survival on univariate analysis included ER-positive/HER2-negative subtype (P = 0.010), KPS ≥ 70 (P < 0.001), LMD as the only site of metastasis (P = 0.004), stable or controlled extracranial metastases (P = 0.042), absence of leukopenia (P = 0.040) and the presence of nodular LMD (P < 0.001). After adjusting for these clinical factors, the receipt of radiation therapy (adjusted hazard ratio [AHR] 0.50, 95% CI: 0.37 - 0.68), systemic therapy (AHR 0.27, 95% CI: 0.19 - 0.38) and intrathecal chemotherapy (AHR 0.49, 95% CI: 0.33 - 0.75) were all associated with improved survival. CONCLUSION In one of the largest multi-institutional reviews to date, we found that several pre-treatment clinical factors were significantly associated with improved survival among women with breast cancer LMD. However, despite treatment overall survival remains poor, and there is a need for new, effective therapies. AUTHOR DISCLOSURE M.G. Milligan: None. A. Aitelli: None. W.A. Mehan: Consultant; Kura Oncology. D.D. Shi: None. D.N. Cagney: Research Grant; Viewray, NhTheraguix. K.S. Oh: None. N. Wang: None. P. Brastianos: Research Grant; Merck, Eli Lily, BMS. Honoraria; Merck, Genentech. Consultant; Angiochem, Dantari Pharmaceuticals, Elevatebio, Eli Lily, Genentech, Pfizer, SK Life Sciences, Tesaro. B. Moy: Research Grant; PUMA biotechnology. N.U. Lin: Research Grant; Genentech, Merck, Pfizer, Seattle Genetics. Consultant; PUMA Biotechnology, Seattle Genetics, Daiichi Sankyo, Astra Zeneca, Denali Therapeutics, California Institute for Regenerative Medicine, Prelude Therapeutics. H.A. Shih: Employee; Dartmouth Hitchcock. Research Grant; AbbVie, NIH. Honoraria; UpToDate. Consultant; Cleveland Clinic. Speaker's Bureau; prIME Oncology. advisory; The Radiosurgery Society. director of clinical operations; Massachusetts General Hospital. clinical operational leader; Massachusetts General Hospital.

Purpose Health care practices across the United States have been consolidating in response to various market forces. The degree of practice consolidation varies widely across specialties but has not been well studied within radiation oncology. This study used Medicare data to characterize the extent of practice consolidation among radiation oncologists and to investigate associated market factors. Methods and Materials We utilized Medicare Provider Enrollment, Chain, and Ownership System data to assess the practice size and billing patterns of U.S. radiation oncologists in 2013 and again in 2017. Individual practices were categorized by the number of radiation oncologists practicing together: solo practices had 1 radiation oncologist, small practices 2 to 10, and large practices 11 or more. Market consolidation within each hospital referral region (HRR) across the country was quantified using the Herfindahl-Hirschman Index. Hospital and market level data were obtained for each HRR, and factors associated with the growth of radiation oncology practices over time were calculated via multivariable linear regression. Results Across the United States, radiation oncology practices appear to be highly consolidated. The mean Herfindahl-Hirschman Index was 0.4711 in 2013—indicating high levels of consolidation at baseline—and increased further to 0.4865 by 2017. Between 2013 and 2017, the number of practices with radiation oncologists in the United States decreased 3.8%, from 1679 to 1615, whereas the number of practicing radiation oncologists increased 9.4%, from 4948 to 5415. Over the study period, the number of solo practices fell 11% (from 708 in 2013 to 627 in 2017), whereas the number of large practices (those with 11 or more radiation oncologists) increased 50% (from 60 to 90). Large practices likewise grew to employ a greater share of all radiation oncologists (23.9%-32.4%) and accounted for a larger proportion of total Medicare billing (21%-26%). Two market factors were predictive for increases in the mean radiation oncology practice size. HRRs with greater hospital market consolidation and those with lower levels of baseline radiation oncology consolidation were more likely to experience higher levels of growth over the study period. Conclusions Radiation oncologists are increasingly working in larger practices. By 2017, nearly one-third of all practicing radiation oncologists in the United States were employed by just the 90 largest practices. Radiation oncology, as a field, is highly concentrated, and represents one of the most consolidated specialties across the country. The implications of practice consolidation among radiation oncologists warrants further investigation.

Purpose/Objective(s) Accurate radiation therapy targeting for stomach cancer is challenging given daily variations in the stomach's size and position. We evaluated daily MR-based imaging to quantify changes in stomach volume and characterized the impact of inter-fractional variation on dosimetry for gastric cancer radiation plans. Materials/Methods We assessed inter-fraction changes in the volume and position of the stomach via MR-based imaging for 10 patients who previously underwent abdominal stereotactic body radiation therapy. All patients were simulated and treated over 5 fractions and were instructed to fast for 3 hours before each session. The stomach and regional organs-at-risk (OARs) were contoured on each fraction's MR scan according to standard RTOG guidelines. Inter-fraction variation in the size and position of the stomach was quantified by calculating the percentage volume change and dice similarity coefficient (DSC) as compared to the simulation scan. To determine the potential impact of inter-fraction stomach motion on treatment planning, we generated mock plans to recapitulate neoadjuvant or definitive stomach cancer treatments. For the purpose of this study, the stomach contour was symmetrically expanded by 1.7 cm to generate a planning treatment volume (PTV) and a prescription dose of 45 Gy in 1.8 Gy fractions was applied. Intensity-modulated radiation therapy plans were then generated to meet the following dosimetric goals: PTV V95% of 95%, liver V30 less than 30%, and bilateral kidney V20 less than 20%. Finally, the impact of gastric variation on these dose metrics was assessed. Results Despite standard daily preparation and set up procedures, we observed significant variability in the size and location of the stomach between fractions. The mean absolute daily change in gastric volume compared to the planning MRI was 19.1% (total range: -42.0% to 58.4%). The average stomach DSC was 0.69 (range: 0.40 to 0.86). Given this degree of variability, mock gastric cancer treatment plans displayed suboptimal dose metrics. The average PTV V45 was 81.5% (range: 58.8% to 99.2%. 95% CI: 78.8% to 84.2%). Average liver V30 values were 12.7% (range: 3.5% to 20.1%. 95% CI: 11.7% to 13.9%) and bilateral kidney V20 values were 12.3% (range: 0.5% to 31.3%. 95% CI: 9.2% to 15.3%). Target metrics were highly correlated with the percent change in stomach volume—a 10% increase in stomach volume was associated with a 2.4% decrease in the V45 (P Conclusion We observed significant inter-fraction variability in the dimensions of the stomach using daily MRI-based imaging, leading to dosimetrically inferior mock gastric cancer treatment plans. Our study suggests that larger PTV margins may be necessary for conventional stomach plans, which would come at the expense of greater OAR exposure. Alternatively, MRI-based image guidance and daily adaptive treatments may improve the therapeutic window of radiation therapy for gastric tumors.

Purpose/Objective(s) To identify risk groups and patterns of recurrence after curative treatment of primary SGT treated with PORT +/- ST. Materials/Methods We retrospectively identified consecutive pts with stage I-IVA SGT, excluding adenoid cystic carcinoma (ca), treated with curative-intent surgery and postoperative IMRT with or without radiosensitizing chemotherapy from 12/2008-02/2020 at a tertiary care center. Pts were classified into clinical risk groups based on histologic diagnoses and pathologic features: (1) low-risk = morphologically low grade (LG) tumors (e.g. acinic cell, secretory, LG mucoepidermoid (MEC), epithelial-myoepithelial, basal cell adenocarcinoma), pN0, without lymphovascular invasion (LVI) or perineural invasion (PNI), including minimally invasive/non-invasive carcinoma ex-pleomorphic adenoma (CXPA); (2) intermediate-risk = intermediate grade morphology (e.g. grade 2 MEC) or LG morphology with PNI or LVI or pN+; (3) high-risk = high grade histology (e.g. salivary duct, high-grade MEC, poorly differentiated ca including invasive CXPA). Kaplan Meier estimates were used for recurrence-free survival (RFS) and univariable predictors. Results 72 pts were included. Median age at surgery was 59.6 years [interquartile range (IQR) 49.7,67.7 yrs]. Sites were: 86% parotid (n = 62), 8% submandibular (n = 6), 4% minor salivary (n = 3), and 1% unknown primary. SGT were classified into clinical risk groups: 26% low (n = 19), 25% intermediate (n = 18), and 49% high-risk (n = 35). Concurrent chemotherapy (CRT) was given to 3% of low-risk (n = 1), 13% of intermediate risk (n = 4), and 71% of high-risk pts (n = 25). Regimens included carboplatin + paclitaxel, cisplatin, and concurrent/adjuvant trastuzumab (in 10 pts with HER2-positive SGT). With a median follow-up of 40.5 months, 2-year OS was 95% (85-98%); there were 11 recurrences (9 distant metastasis (DM), 2 in-field local failure (LF) both in pts with gross residual after surgery), with 82% (9 of 11) having received CRT. All recurrences were in the high-risk group with 2-year RFS of 73% (54%-85%) and 2-year cumulative incidence of DM 21% and LF 6%. Factors associated with RFS included positive margins (P = 0.004) and low-neck positive lymph nodes (level III/IV/V vs. level I/II, P = 0.04). Thirteen pts (18%) had targeted genomic sequencing (4 with recurrence); common mutations included TP53 (n = 4), HRAS (n = 3), NFKBIZ (n = 3), and PIK3CA (n = 3). Mutations in NF1 (n = 3) and HNFA1 (n = 2) were observed only in pts that recurred. Conclusion DM are the primary mode of recurrence in pts with resected SGT treated with PORT +/- ST and occurred only in high-risk pts. After randomized trials like RTOG 1008 determine the added benefit of chemo to PORT, DM is likely to remain an unmet need. Further studies incorporating molecular characterization of high-grade SGT may identify potentially actionable targets to prevent distant recurrence.