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Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG).

ABSTRACT: BRAF kinase gene V600 point mutations drive approximately 40% to 50% of all melanomas, and BRAF inhibitors (BRAFi) have been found to significantly improve survival outcomes. Although radiation therapy (RT) provides effective symptom palliation, there is a lack of toxicity and efficacy data when RT is combined with BRAFi, including vemurafenib and dabrafenib. This literature review provides a detailed analysis of potential increased dermatologic, pulmonary, neurologic, hepatic, esophageal, and bowel toxicity from the combination of BRAFi and RT for melanoma patients described in 27 publications. Despite 7 publications noting potential intracranial neurotoxicity, the rates of radionecrosis and hemorrhage from whole brain RT (WBRT), stereotactic radiosurgery (SRS), or both do not appear increased with concurrent or sequential administration of BRAFis. Almost all grade 3 dermatitis reactions occurred when RT and BRAFi were administered concurrently. Painful, disfiguring nondermatitis cutaneous reactions have been described from concurrent or sequential RT and BRAFi administration, which improved with topical steroids and time. Visceral toxicity has been reported with RT and BRAFi, with deaths possibly related to bowel perforation and liver hemorrhage. Increased severity of radiation pneumonitis with BRAFi is rare, but more concerning was a potentially related fatal pulmonary hemorrhage. Conversely, encouraging reports have described patients with leptomeningeal spread and unresectable lymphadenopathy rendered disease free from combined RT and BRAFi. Based on our review, the authors recommend holding BRAFi and/or MEK inhibitors ?3 days before and after fractionated RT and ?1 day before and after SRS. No fatal reactions have been described with a dose <4 Gy per fraction, and time off systemic treatment should be minimized. Future prospective data will serve to refine these recommendations.

SUBMITTER: Anker CJ

PROVIDER: S-EPMC5102246 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG).

Anker Christopher J CJ Grossmann Kenneth F KF Atkins Michael B MB Suneja Gita G Tarhini Ahmad A AA Kirkwood John M JM

International journal of radiation oncology, biology, physics 20160601 2

BRAF kinase gene V600 point mutations drive approximately 40% to 50% of all melanomas, and BRAF inhibitors (BRAFi) have been found to significantly improve survival outcomes. Although radiation therapy (RT) provides effective symptom palliation, there is a lack of toxicity and efficacy data when RT is combined with BRAFi, including vemurafenib and dabrafenib. This literature review provides a detailed analysis of potential increased dermatologic, pulmonary, neurologic, hepatic, esophageal, and b ...[more]

PMID: 27131079

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Project description:PurposeClinical trials have described variation in radiation therapy plan quality, of which contour delineation is a key component, and linked this to inferior patient outcomes. In response, consensus guidelines have been developed to standardize contour delineation. This investigation assesses trends in contouring guidelines and examines the methodologies used to generate and deliver recommendations.Methods and materialsWe conducted a literature search for contouring guidelines published after 1995. Of 11,124 citations, 332 were identified for full-text review to determine inclusion. We abstracted articles for the intent of the consensus process, key elements of the methodology, and mode of information delivery. A Fisher exact test was used to identify elements that differed among the guidelines generated for clinical trials and routine care.ResultsOverall, 142 guidelines were included, of which 16 (11%) were developed for a clinical trial. There was an increase in guideline publication over time (0 from 1995-1999 vs 65 from 2015- 2019; P = .03), particularly among recommendations for stereotactic radiation and brachytherapy. The most common disease sites were head and neck (24%), gastrointestinal (12%), and gynecologic (12%). Methods used to develop recommendations included literature review (50%) and image-based methods (45%). Panels included a median of 10 physicians (interquartile range, 7-16); 70% of panels represented multidisciplinary expertise. Guidelines developed for a clinical trial were more likely to include an image-based approach, with quantitative analysis of contours submitted by the panel members and to publish a full set of image-based recommendations (P < .005).ConclusionsThis review highlights an increase in consensus contouring recommendations over time. Guidelines focus on disease sites, such as head and neck, with evidence supporting a correlation between treatment planning and patient outcomes, although variation exists in the approach to the consensus process. Elements that may improve guideline acceptance (ie, image-based consensus contour analysis) and usability (ie, inclusion of a full image set) are more common in guidelines developed for clinical trials.

Dataset Information

Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG).

Publications

Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG).

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