Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2015-07, Vol.17 (7), p.1022-1028
• Main Authors: Wang, Tony J C, Saad, Shumaila, Qureshi, Yasir H, Jani, Ashish, Nanda, Tavish, Yaeh, Andrew M, Rozenblat, Tzlil, Sisti, Michael B, Bruce, Jeffrey N, McKhann, Guy M, Lesser, Jeraldine, Halmos, Balazs, Stoopler, Mark B, Lassman, Andrew B, Cheng, Simon K, Isaacson, Steven R
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Brain Neoplasms - genetics; Brain Neoplasms - mortality; Brain Neoplasms - radiotherapy; Brain Neoplasms - secondary; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Cycle Proteins - genetics; Clinical Investigations; Epidermal Growth Factor - genetics; Female; Humans; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Microtubule-Associated Proteins - genetics; Middle Aged; Mutation; Proportional Hazards Models; Proto-Oncogene Proteins p21(ras) - genetics; Radiosurgery; Receptor Protein-Tyrosine Kinases - genetics; Serine Endopeptidases - genetics
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nov043

We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC). A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population. Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P = .019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P = .071). Targeted therapy was a strong predictor of increased OS on univariate (P = .037) and multivariate (P = .022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P < .05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95% CI: 2.0-33.7; P = .003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P = .471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P = .577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7%, 5.4%, 4.3%, and 5.1%, respectively. This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.