BMET-22. DOES WHOLE BRAIN RADIOTHERAPY FOR OLIGOMETASTATIC BRAIN METASTASES TRANSLATE INTO A SURVIVAL BENEFIT FOR PATIENTS WITH A LIMITED COMPETING RISK FROM EXTRA-CRANIAL DISEASE? A SECONDARY ANALYSIS OF EORTC 22952-26001

Abstract

Purpose/Objective(s): The failure of randomized trials to find a survival benefit for whole brain radiation (WBRT) has been attributed to a competing risk of death from extra‐cranial disease. We assessed the survival benefit of WBRT for patients with controlled extra‐cranial disease and those with favorable disease‐specific graded prognostic assessment (GPA) scores within EORTC 22952. Materials/Methods: In the EORTC 22952 trial, patients with 1‐3 brain metastases with stable systemic disease or asymptomatic primary tumors were randomized to WBRT versus observation prior to stereotactic radiosurgery (SRS) or after surgical resection. We performed an exploratory analysis using Cox regression and Kaplan‐Meier analysis to evaluate overall survival according to receipt of WBRT, accounting for (1) extracranial progression (evidence of progressive disease outside the brain) and (2) calculated GPA score (unfavorable = [0.5‐2.0] or favorable = [2.5‐4.0]). We adjusted for performance status, primary site, number of metastases, and initial presence of extracranial disease in multivariable analysis including time to extracranial progression as a time‐dependent covariate. Results: A total of 358 patients were included for analysis with a median follow up of 6.5 months. The most common primary site was lung (53%) followed by breast (12%), colorectal (8%), and kidney (8%). Ninety‐three of 196 patients undergoing SRS and 79 of 162 patients undergoing surgery were randomized to WBRT. A total of 140 (39%) patients had no extracranial progression, while 81 (23%) patients had extracranial progression <90 days, 57 (16%) patients between 90 and 180 days, and 80 (22%) patients >180 days. Overall, there was no significant interaction between the effect of WBRT and time to extracranial progression (P = 0.25) on overall survival. Although model‐based risk of death was lower for the WBRT group before extracranial progression (HR [95% CI] = 0.81 [0.54‐1.22]), this was not statistically significant (P = 0.32). There was no significant difference between WBRT groups after extracranial progression (HR [95% CI] = 1.10 [0.81‐1.49]). Two hundred sixty‐six patients had data for GPA calculation with the majority (72%) representing lung cancer. There was no overall survival benefit to WBRT among patients with favorable GPA scores (P = 1.00) or unfavorable GPA scores (P = 0.87). Conclusion: After careful patient selection, we were unable to find a subset of patients with controlled extracranial disease or favorable GPA scores that benefited from the addition of WBRT. This secondary analysis of phase III data further supports the omission of WBRT for patients with 1‐3 brain metastases undergoing SRS or surgery and close surveillance.