Non-small cell lung cancer molecular alterations impact on brain metastases response to gamma knife radiosurgery: Identification of potential radiosensitive tumor phenotypes

Abstract

Introduction Results from clinical studies regarding the radiosensitivity of non-small cell lung cancer (NSCLC) brain metastases (BMs) are scarce and inconclusive. Indeed, little is known about the actual impact of the primary tumor molecular profile and radiological response to radiosurgery. We report here the analysis of a prospective patient cohort of NSCLC patients harboring BMs treated by gamma knife radiosurgery and investigated whether the primary tumor molecular phenotype had an actual impact on BM radiosensitivity. Materials and methods Two hundred sixty three patients were enrolled between January 2010 and April 2013. Molecular profile was available for 90 patients. Local and distant brain control was determined for these 90 patients harboring 173 BMs. Radiological assessment using MRI-scans was undertaken every 3 months after radiosurgery. Patient-, tumor- and treatment-related data were included. Log-rank test and Cox regression model were used to correlate molecular profile of the primary tumor and other clinical features to intracranial radiological control. Results In total, 48/90 (53.3%) of patients presented molecular alterations, 25/90 (27.8%) had KRAS mutations, 16/90 (17.8%) had EGFR mutations, 3/90 (3.3%) had ALK translocation, and 4 patients other genetic alterations. Overall, local and distant control was achieved in 83/90 (92.2%) and in 39/90 (43.4%) patients respectively. No local treatment failure was observed in EGFR mutant or ALK translocated tumor. One (4%) of the 25 KRAS mutated patients experienced a local failure. In the 42/90 patients (46.7%), local failure occurred in 4 cases (9.5%). Multivariate analysis demonstrated that EGFR mutation status and ALK translocation were independent predictors of better local control in patients treated by gamma knife radiosurgery. Conclusion EGFR mutation and ALK translocation are independent prognostic factor regarding local control after Gama Knife radiosurgery in NSCLC patients with BM. The results provided here suggest that molecular profile of NSCLC patient might be taken in account in treatment decision strategy.