The Impact of Tumor Biology on Survival and Response to Radiation Therapy among Patients with Non-Small Cell Lung Cancer Brain Metastases

Publication date: Available online 5 January 2017
Source:Practical Radiation Oncology
Author(s): Jacob A. Miller, Rupesh Kotecha, Manmeet S. Ahluwalia, Alireza M. Mohammadi, John H. Suh, Gene H. Barnett, Erin S. Murphy, Michael A. Vogelbaum, Lilyana Angelov, Samuel T. Chao
PurposeTo investigate the natural history and response to radiation therapy among ALK-rearranged, EGFR-mutated, wild-type adenocarcinoma, and squamous cell non-small cell lung cancer (NSCLC) brain metastases.Materials and MethodsPatients with NSCLC brain metastasis diagnosed from 1989–2014 at a single tertiary-care institution were included. The primary outcome was overall survival, while secondary outcomes included local failure, distant intracranial failure, and radiation necrosis. Cox proportional hazards regression was used to model overall survival, while multivariate competing risks regression was used to model secondary outcomes.ResultsWithin the study period, 1920 patients presented with 6312 brain metastases. Squamous histology was associated with poorer median survival compared with adenocarcinomas (5.4 vs. 8.8 mo., p<0.01). Median survival was greatest among ALK+ patients (49.2 mo.), followed by EGFR+ (20.3 mo.), and wild-type adenocarcinomas (10.0 mo., p<0.01). Treatment with EGFR inhibitors (HR 0.66, p<0.01) and VEGF antibodies (HR 0.65, p<0.01) increased survival independent of mutational status.Among 2056 lesions treated with stereotactic radiosurgery, the 12-month cumulative incidence of local failure was significantly greater among squamous cell carcinomas relative to adenocarcinomas (15% vs. 10%, HR 1.26, p=0.04). Patients with ALK+ metastases experienced higher rates of local failure (10%, HR 2.00, p=0.05), distant failure (39%, HR 2.94, p<0.01), and radiation necrosis (18%, HR 5.77, p<0.01), while EGFR+ patients experienced the lowest rates of local failure (5%, HR 0.46, p=0.04) and distant failure (3%, HR 0.13, p=0.04).ConclusionsAdvances in precision medicine have increased survival among select patients with NSCLC. In the present investigation, ALK+ and EGFR+ status were associated with improved survival. However, patients with ALK+ metastases have poor intracranial control relative to EGFR+ metastases, possibly due to limited intracranial penetration of crizotinib compared to EGFR inhibitors. Future investigations are warranted to determine the optimal management of ALK+ brain metastases with the introduction of second-generation ALK inhibitors.



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