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Purpose: To determine whether phosphatidylinositol-3-kinase (PI3K) mutations confer suboptimal local control after radiation therapy (RT) for brain metastases.Methods and Materials: 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.Results: A total of 112 patients received whole brain radiation therapy (WBRT) to a median dose of 30 Gy in 10 fractions, and 147 patients received stereotactic radiosurgery (SRS) to 338 lesions; 276 lesions were treated with single fraction SRS (median dose 21 Gy) and 76 lesions over 3 to 5 fractions SRS (median dose 30 Gy). 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background and purpose Hypofractionated conformal radiotherapy (hfCRT) is used for larger brain metastases or metastases near critical structures. We investigated hfCRT outcomes for newly diagnosed brain metastases. Materials and methods We identified 195 patients with 1–3 brain metastases who underwent 5 × 6 Gy hfCRT for 231 lesions from 2007 to 2013. Associations among clinical factors, local control (LC), distant brain control (DC) and overall survival (OS) were tested using univariate and multivariate (MVA) Cox regression analysis and Kaplan–Meier method. Results Median follow-up was 12.8 months. One hundred forty-three (62%) lesions were treated with hfCRT post-operatively, and 88 (38%) with definitive hfCRT. LC for all lesions was 83% at 1 year. For lesions treated with post-operative hfCRT, tumor size (HR = 4.7, p = 0.04) and subtotal resection (HR = 2.7, p = 0.02) were predictive of local failure on MVA. For lesions ≥2.8 cm in size, LC was 61% at 12 months for lesions status-post subtotal resection, compared to 84% status-post gross total resection ( p = 0.004). Extracranial disease presence was associated with worse DC (HR = 1.8, p = 0.008) and OS (HR = 3.1, p < 0.001). Conclusions We showed 5 × 6 Gy hfCRT provides acceptable LC at 1 year for limited brain metastases. For large lesions not grossly resected, more aggressive strategies can be considered to improve LC. [ABSTRACT FROM AUTHOR]