Phosphatidylinositol-3-Kinase Mutations Are Associated With Increased Local Failure in Brain Metastases Treated With Radiation

Abstract

Todetermine whether phosphatidylinositol-3-kinase (PI3K) mutations confer suboptimal local control after radiation therapy (RT) for brain metastases. We retrospectively reviewed 259 patients with brain metastases treated with RT during the period 2004 to 2017 for whom tumor genetic data (MSK-IMPACT) were available for primary or metastatic lesions. Associations between clinical factors, PI3K mutations status, and local failure (LF) were evaluated with univariate and multivariate competing risks regression. A total of 112 patients received whole brain radiation therapy (WBRT) to a median dose of 30Gy in 10 fractions, and 147 patients received stereotactic radiosurgery (SRS) to 338 lesions; 276 lesions were treated with single fraction SRS (median dose 21Gy) and 76 lesions over 3 to 5 fractions SRS (median dose 30Gy). PI3K mutations were present in 36 WBRT patients (32%) and 44 SRS patients (30%). For WBRT, patients with PI3K mutations (hazard ratio 2.67, P<.001) were found to be at higher risk for LF on multivariable analysis, and the 1-year cumulative incidence of LF was 50% (95% confidence interval [CI] 32%-65%) for patients with PI3K mutations versus 26% (95% CI 17%-37%) for patients without PI3K mutations. For SRS lesions, while PI3K mutations positivity was not statistically significantly associated with LF, higher rate of LF was observed: 1-year LF cumulative incidence of 11% (95% CI 6%-17%) for patients with PI3K mutations versus 5% (95% CI 3%-9%) for patients without PI3K mutations. Patients with PI3K mutations are at higher risk for LF for brain metastases after RT. Novel therapeutic strategies to improve treatment outcomes in these patients should be considered.