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.
The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.
Importance Evolving data on the effectiveness of post-mastectomy radiation therapy (PMRT) have led to changes in NCCN recommendations, counseling providers to “strongly consider” PMRT for breast cancer patients with tumors ≤5cm and 1-3 positive nodes; however, anticipated PMRT may lead to delay or omission of reconstruction which can have cosmetic, quality of life, and complication implications for patients. Objective To determine whether revised guidelines have increased PMRT and impacted receipt of breast reconstruction. We hypothesized that: 1) PMRT would increase for women affected by the revised guidelines while remaining stable in other cohorts, and 2) that these women would have decreased receipt of breast reconstruction while reconstruction increased in other groups. Design A retrospective, population-based cohort study Setting Surveillance, Epidemiology, and End Results (SEER) data from 2000 – 2011. Participants Women with stage I-III breast cancer undergoing mastectomy were identified. Our analytic sample (n=62,442) was divided into cohorts based on current NCCN radiation recommendations: “Radiation Recommended” (tumors >5 cm or ≥4 positive lymph nodes), “Strongly Consider Radiation” (tumor ≤5cm, 1-3 positive nodes), and “Radiation Not Recommended” (tumors ≤5cm, no positive nodes). Main Outcome Measure(s) We used joinpoint regression analysis to evaluate temporal trends in our outcomes of interest: receipt of PMRT and receipt of breast reconstruction. Results Rates of PMRT were unchanged in the “Radiation Recommended” and “Radiation Not Recommended” cohorts over the study period. In contrast, receipt of PMRT for the “Strongly Consider Radiation” cohort was unchanged until 2007, then significantly increased (APC 9.0%, p=0.013). Breast reconstruction increased across all cohorts. Despite increasing receipt of PMRT, the “Strongly Consider Radiation” cohort maintained a consistent increase in reconstruction (APC 7.5%) throughout the study period. This is similar to the increase in reconstruction observed for the “Radiation Recommended” (10.7%) and “Radiation Not Recommended (8.4%) cohorts. Conclusions and Relevance NCCN guideline changes have increased PMRT receipt for patients with tumors ≤5cm and 1-3 positive nodes without an associated decrease in receipt of reconstruction. This may represent increasing provider comfort with the prospect of irradiating a new breast reconstruction, and may have significant cosmetic and quality of life implications for patients.
Purpose To standardize upper abdominal normal organ contouring guidelines for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials Twelve expert radiation oncologists contoured the liver, esophagus, gastroesophageal junction (GEJ), stomach, duodenum, and common bile duct (CBD), and reviewed and edited 33 additional normal organ and blood vessel contours on an anonymized patient computed tomography (CT) dataset. Contours were overlaid and compared for agreement using MATLAB (MathWorks, Natick, MA). S95 contours, defined as the binomial distribution to generate 95% group consensus contours, and normal organ contouring definitions were generated and reviewed by the panel. Results There was excellent consistency and agreement of the liver, duodenal, and stomach contours, with substantial consistency for the esophagus contour, and moderate consistency for the GEJ and CBD contours using a Kappa statistic. Consensus definitions, detailed normal organ contouring recommendations and high-resolution images were developed. Conclusions Consensus contouring guidelines and a CT image atlas should improve contouring uniformity in radiation oncology clinical planning and RTOG trials.
Equivalent 5-year PFR and toxicity rates are shown for patients with vestibular schwanoma selected for SRS, HypoFSRT, and ConFSRT after multidisciplinary evaluation. Factors correlating with tumor progression included NF2 and larger tumor size.
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