Rthp-33. Pik3 Mutations Are Associated With Decreased Local Control in Brain Metastases Treated With Radiation
Year: 2017
Type: conference-abstract
Abstract: Hyperactivation of the phosphatidylinositol-3-kinases (PI3K) pathway has been reported to be associated with radioresistance in preclinical models. We examined whether PIK3 mutations are associated with poor radiation (RT) response in brain metastases (BM). We retrospectively reviewed 259 patients with BM treated with RT from 2004-2017 for whom MSK-IMPACT testing data was available for primary or metastatic lesions. MSK-IMPACT analyzes 341 genes, including PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2 and PIK3R3. Association between clinical factors, mutation status, and local control (LC) was evaluated with Cox regression multivariate analysis. The Kaplan-Meier method was used to assess differences in LC rates and overall survival (OS). 147 patients received stereotactic radiation (SRS) and 112 patients received whole brain radiation (WBRT). The most common histologies were lung (48%) and breast (20%). Eighty-three (32%) patients had PIK3 mutations, and 36 (14%) patients specifically had PIK3CA mutations. Median follow-up was 10.8 months. LC was 82% at 12 months. The presence of any PIK3 mutation (HR=0.4, p<0.001), PIK3CA mutation (HR=0.7, p=0.006), and receipt of WBRT (HR=0.1, p<0.001) were associated with decreased LC, while age and histology were not. For patients who received WBRT, mutation status resulted in worse LC at 12-months: 42% for PIK3 mutation positive vs. 65% for mutation negative, p<0.001; 50% for PIK3CA mutation positive vs. 60% for mutation negative, p=0.002. Interestingly, for SRS treatments, PIK3 mutation positivity did not result in worse LC at 12 months (90% vs. 93% mutation negative, p=0.17), while PIK3CA mutation positivity did (76% vs. 92% mutation negative, p=0.05). There was no difference in OS based on PIK3 mutation status. Patients with PIK3 mutations are at significantly higher risk for decreased LC after RT for BM. Specifically, patients with PIK3CA mutations are more likely to developed local recurrence that is not abrogated by SRS.
Source: Neuro-Oncology
Authors: Natalie Lockney, Diana Wang, Andrew Lin, Xin Pei, Timothy Chan, Yoshiya Yamada, Kathryn Beal, T Jonathan Yang
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767736497