Molecular markers are redefining classification of lower grade gliomas and ushering in a paradigm shift in their management. Our objective was to evaluate the differences in pattern of care and outcome by comparing grade II and grade III molecularly defined 1p19q co-deleted gliomas. We evaluated 1618 patients in the National Cancer Database diagnosed with 1p19q co-deleted gliomas from 2010 through 2014 and treated with surgery followed by radiation therapy (RT), chemotherapy (CT), or combined-modality therapy. Differences in patterns of care included that fifty-one percent of grade II tumors received surgery alone, whereas most patients with grade III tumors (86%) received surgery or biopsy followed by a form of post-operative therapy (p < 0.001). In a propensity score matched cohort, the Cox multivariable proportional hazards model with frailty testing identified significant covariates were age, comorbidity, histology and grade. Outcomes were different in overall survival even after adjusting for treatment received. The hazard for death for grade III 1p19q co-deleted gliomas was about 3.6 times higher ([HR] 3.69, 95% confidence interval [CI] 2.03-6.68, p < 0.001) than grade II 1p19q gliomas. Oligodendroglioma histology was associated with a lower likelihood of death (HR 0.40, 95% CI 0.230.70, p < 0.001). Our study is among the largest series to report on 1p19q co-deleted gliomas, which would otherwise require decades to acquire outside of large databases. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.

Importance: Preoperative stereotactic radiation therapy (SRT) vs postoperative SRT logistics and toxic effects provides clinically significant data on management outcomes.Objective: To determine preoperative SRT logistics and safety profile compared with postoperative in patients with brain metastases.Design, Setting, and Participants: This single-institution phase 3 randomized clinical trial included patients 18 years and older and undergoing a planned surgical resection. Patients were required to have an Eastern Cooperative Oncology Group Performance Status score of 2 or greater and be candidates for SRT within 30 days of surgical resection. Patients with radiosensitive histologies (eg, small cell lung cancer and lymphoma), brain metastasis of unknown primary, and/or radiographic evidence of leptomeningeal disease were excluded. Data were collected from December 2018 to August 2023, and data were analyzed from September 2023 to December 2024.Interventions: Patients were randomized 1:1. Patients randomized to the preoperative SRT cohort underwent SRT (in 1 to 5 fractions) followed by surgical resection within 1 month of radiation therapy. Patients randomized to the postoperative SRT cohort underwent resection followed by postoperative SRT within 1 month of surgery.Main Outcomes and Measures: Outcomes reported focus on nonprimary end point analysis of the trial, including comparative toxic effect outcomes of preoperative vs postoperative SRT postprocedural events, feasibility of preoperative SRT, and radiation therapy management.Results: Of 103 patients, 56 (54.4%) were male, and the median (range) age was 59 (26-83) years. Of 103 patients, 83 (80.6%) completed both radiation and surgery for brain metastases while in the study. Of these, 70 patients (84%) had 1 to 4 brain metastases at enrollment, 11 (13%) had 5 to 10 lesions, and 2 (2%) had more than 10 lesions. In the preoperative stereotactic radiosurgery (SRS)/SRT cohort, 45 (88%) completed both treatments compared with 38 (73%) in the postoperative SRS/SRT arm. There were no statistically significant differences between treatment groups in 30-day postoperative morbidity or postprocedural events. The median (range) time between surgery and SRT was significantly shorter in the preoperative arm (6 [0-24] days) compared with the postoperative arm (22 [12-42] days; P < .001). The median (range) time from randomization to receiving both brain-directed therapies was 10 (4-31) days in the preoperative arm compared with 32.5 (19-55) days for the postoperative arm (P < .001).Conclusions and Relevance: In this randomized clinical trial, preoperative SRT had comparable safety to postoperative SRT and resulted in shorter time to treatment completion, potentially facilitating expedited care.Trial Registration: ClinicalTrials.gov Identifier: NCT03741673

Purpose: Molecular glioblastoma (molGBM) is a variant lacking the full histopathological profile of glioblastoma. We report a trial aimed at addressing the optimal management of this newly recognized rarer form of glioma. Methods: In this phase II study, molGBM patients were treated with radiation to a dose of 60Gy to the gross tumor volume (GTV) only, and a single smaller margin potentially as low as 1cm to the clinical tumor volume (CTV). As the trial is ongoing, we report on important exploratory biomarker findings correlating with median overall survival (mOS). Analysis included Kaplan-Meier and univariable/multivariable cox proportional hazard models. Available pre-operative tissue was subjected to epigenetic/DNA methylation profiling on the Infinium EPIC platform. Results: From 2019 to 2023, 25 patients were enrolled based on initial pathology review, with 23 identified on 2nd review as grade 2 and 3 disease. 74% of patients received concurrent chemoradiotherapy with adjuvant chemotherapy. Of 9 patients with profiling, 5 were classified as mesenchymal subtype, while 4 matched to a variety of other phenotypes, including a novel F type GBM. Despite similar histological appearance corresponding to “lower grade glioma”, molGBM classified as IDH-wildtype mesenchymal had mOS of 15.7 months (95% CI 15.5-NA) while the other tumors had a mOS of 37.7 months (95% CI 10.9-NA). Conclusion: Our results demonstrate underlying heterogeneity within the molGBM population, pointing to future hypothesis-generating risk stratification strategies. We also demonstrate the feasibility of CTV reduction with therapy intensification to set a practice standard for RT management of non-enhancing molGBM.