Transcriptional diversity of long-term glioblastoma survivors

BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. METHODS: We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival \u3e48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs. RESULTS: The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs. CONCLUSIONS: While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression

Radiation in Early-Stage Breast Cancer: Moving beyond an All or Nothing Approach

Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens’ decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions

Different Re-Irradiation Techniques after Breast-Conserving Surgery for Recurrent or New Primary Breast Cancer

Breast re-irradiation (reRT) after breast-conserving surgery (BCS) using external beam radiation is an increasingly used salvage approach for women presenting with recurrent or new primary breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. There is also limited data on efficacy and safety of external beam hypofractionation and accelerated partial-breast irradiation (APBI) regimens. This paper reviews existing retrospective and prospective data for breast reRT after BCS, APBI reRT outcomes and delivery at our institution and the need for a randomized controlled trial using shorter courses of radiation to better define patient selection for different reRT fractionation regimens

Current Social Media Use Among Radiation Oncology Trainees

Resident physicians use social media (SM) for many reasons. We sought to characterize current SM use by radiation oncology (RO) trainees for education and professional development. An anonymous 40-question survey was sent by e-mail to RO residents in the 2018 to 2019 academic year. SM platform use, time spent on SM, professional use, and opinions regarding SM use were assessed. Descriptive statistics and a univariate logistic regression analysis were performed to identify factors associated with perceptions of SM and spending >25% of SM time for academic or professional purposes. Of the 615 residents surveyed, 149 responded (24% response rate). Facebook (73%), theMednet (62%), Instagram (59%), Twitter (57%), and Doximity (50%) were the top SM platforms used. Most respondents (53%) reported 60 minutes per day over the past week. Residents with an RO mentor on SM (n = 35; 24%; odds ratio [OR]: 2.79; 95% confidence interval [CI], 1.29-6.08; P = .010), those participating in RO discussions on SM (n = 71; 48%; OR: 2.85; 95% CI, 1.42-5.72; P = .003), and those interacting with professional societies (n = 69; 46%; OR: 7.11; 95% CI, 3.32-15.24; P 25% of their SM time on professional/academic purposes. The vast majority of respondents agreed that SM exposed them to novel educational content (82%) and was helpful for career development (65%). In addition, 69% agreed that SM can improve clinical skills and knowledge. A substantial minority agreed that SM distracts them from studying (38%) or they felt pressure to have a SM presence (29%). Most RO residents reported that SM provides novel educational content and can help with career development. Potential disadvantages of SM for trainees may include distraction and pressure to maintain a SM presence. SM use by RO trainees merits further research to optimize its potential for education and professional development

Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. METHODS: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns. CONCLUSIONS: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI