Title | Phosphatidylinositol-3-Kinase Mutations Are Associated With Increased Local Failure in Brain Metastases Treated With Radiation. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Lockney NA, Wang DG, Pei X, Goldman DA, Zhang Z, Lin A, Chan TA, Yamada Y, Beal K, T Yang J |
Journal | Int J Radiat Oncol Biol Phys |
Volume | 101 |
Issue | 4 |
Pagination | 833-844 |
Date Published | 2018 07 15 |
ISSN | 1879-355X |
Keywords | Adult, Aged, Aged, 80 and over, Analysis of Variance, Brain Neoplasms, Confidence Intervals, Cranial Irradiation, Dose Fractionation, Radiation, Female, Humans, Male, Middle Aged, Mutation, Phosphatidylinositol 3-Kinase, Radiosurgery, Retrospective Studies, Treatment Failure, Young Adult |
Abstract | 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. |
DOI | 10.1016/j.ijrobp.2018.03.032 |
Alternate Journal | Int. J. Radiat. Oncol. Biol. Phys. |
PubMed ID | 29976496 |
Grant List | P30 CA008748 / CA / NCI NIH HHS / United States |
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