S. N. Mazur1, S. Dacic2, J. D. Luketich1, M. J. Schuchert1 1University of Pittsburgh Medical Center,Cardiothoracic Surgery,Pittsburgh, PA, USA 2University of Pittsburgh Medical Center,Pathology,Pittsburgh, PA, USA
Introduction: Brain metastases are arguably one of the most feared and devastating consequences of lung cancer. Previous studies have found a relationship between Epidermal Growth Factor Receptor (EGFR) mutations and brain metastasis, especially in Asian populations where a higher rate of EGFR mutations has been observed. A potential link between Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which are quite prevalent in Western non-small cell lung cancer (NSCLC) patients, and brain metastasis has been largely unexamined. In this study, we evaluated the prevalence of molecular mutations in patients with biopsy-proven brain metastases. We hypothesized that there would be a significantly higher number of lung cancer patients with brain metastasis who also harbored a KRAS mutation.
Methods: Retrospective review of all patients undergoing anatomic lung resection (segmentectomy or lobectomy) for primary lung adenocarcinoma with biopsy-proven brain metastases from 2002-2017. Molecular testing data was derived from pathology report summaries. Molecular mutations analyzed include KRAS (primarily codon 12/13) and EGFR (primarily exons 19 and 21). Primary outcome variables included molecular expression patterns and overall survival. Significance of molecular expression was assessed with the Fisher’s Exact test. Survival curves were analyzed utilizing the Kaplan-Maier method, with significance being assessed by the log rank test.
Results: Seventy patients with biopsy-proven brain metastases were identified. Among these, 17 (24.3%) of patients had brain metastases at the time of clinical presentation prior to lung resection. The remaining 53 patients developed brain metastases subsequent to lung resection (median time to brain metastasis = 19.5 months, range: 1.8 – 99.7 months). The average patient age was 62.1 years, and there were 37 male patients (53.0%). Twenty-two patients received neoadjuvant treatment prior to surgery. Molecular testing was performed in 56 (80.0%) of patients. KRAS mutations were identified in 22/56 (39.2%), and EGFR mutations were identified in 4/56 (7.1%) patients undergoing testing [p<0.0001]. The most common KRAS mutation was G12C (59.1% of KRAS-positive patients). The difference in survival time between KRAS-mutated patients and EGFR-mutated patients was not significant (p = 0.67). Likewise, the difference in survival time between KRAS-mutated patients and patients who were wild-type for both KRAS and EGFR was not significant (p = 0.39).
Conclusions: An increased rate of KRAS mutations is noted in patients with brain metastases in the setting of resected lung adenocarcinoma. This may mean that the presence of KRAS mutations could play a larger role in the development of brain metastases in Western populations. The presence of KRAS mutations does not appear to affect overall survival.