Association Of Response To Whole-Brain Irradiation Of Brain Metastases With Molecular Profile In Non-Small Cell Lung Cancer.

9096 Background: Brain metastases (BM) are one of the common sites of disease progression in non-small-cell-lung-cancer (NSCLC) and lead to treatment failure and impaired quality of life. We determined the impact of genetic alterations in EGFR, ALK and KRAS on the objective response rate (ORR), intracranial progression-free survival (IPFS) and overall survival (OS) of patients with BM after whole-brain irradiation (WBI). Methods: From January 2009 through June 2015, 231 NSCLC patients with BM at diagnosis were reviewed for eligibility. Among them, 121 patients were treated with WBI and without concurrent chemotherapy or tyrosine kinase inhibitors (TKIs) and have available genotyping status. Results: EGFR, KRAS, ALK and WT patients were found in 38.0%, 6.6%, 5.8% and 49.6%, respectively. Overall, ORR and disease control rate (DCR) were 61.2% and 76.0%, respectively. ORR for EGFR, KRAS, ALK and WT patients were 82.6%, 28.6%, 71.4% and 50.0%, respectively (P =0.002). EGFR was the only independent factor associated to treatment response to WBI (OR 8.9 [95% CI 2.2-35.2], P <0.001). High grade and KRAS mutations were independently associated with resistance to WBI. Median IPFS was 6.17 months [95% CI 4.6 -7.6]. IPFS for EGFR, KRAS, ALK and WT patients were 7.1, 4.5, 12.1 and 5.1 months, respectively (P =0.004). EGFR mutation status (HR 0.58 [95%CI 0.3-0.8], P =0.015) and KPS at BM ≥ 70 (HR 0.26 [95%CI 0.1-0.8], P =0.020) were associated with higher IPFS in the multivariate Cox-regression analysis. Median OS was 9.1 months [95% CI 7.4-10.9]. OS for EGFR, KRAS, ALK and WT patients were 9.3, 4.9, 12.1 and 9.2 months, respectively (P <0.001). Only intracranial objective response was associated with a higher OS (HR 0.25 [95%CI 0.1-0.4], P <0.001), while KRAS mutation positive status (HR 4.65 [95%CI 1.6-13.5], P =0.005) and carcinoembrionic-antigen ≥ 20 pg/ml at diagnosis (HR 1.48 [95%CI 1.1-2.1], P =0.039) were independently associated with worse OS. Conclusions: EGFR mutation is an independent predictive factor for objective response to WBI without concurrent TKI for BM in patients with NSCLC. KRAS mutation is an independent predictive factor for both BM treatment resistance and worse OS after BM.