MLTI-02. Impact of driver mutations on timing, pattern, treatment, and outcome in patients with brain metastases from non-small cell lung cancer

OBJECTIVE: To assess the impact of driver mutations in non-small cell lung cancer (NSCLC) on the formation and treatment outcome of brain metastases (BM). PATIENTS AND METHODS: We retrospectively analyzed patients with BM from NSCLC with respect to driver mutations and assessed timing and pattern of BM development as well as local cerebral control and survival after BM treatment. RESULTS: We included 253 patients. Histology was adenocarcinoma in 223, squamous cell carcinoma in 25 and not otherwise specified (NOS) in five patients. All tumors were analyzed for known alterations in NSCLC by panel sequencing and fluorescence in situ hybridization (FISH). An activating KRAS mutation (n=85) was the most prevalent mutation, followed by activating EGFR mutation (n=31) and MET amplification (n=29). Other mutations were detected in 27 patients. No alterations were found in 102 patients. Time to BM development did not differ between the molecular groups (p=.22), nor did the number (p=.72) or location (supra- vs. infratentorial; p=.76) of the BM. Patients underwent multimodal cerebral treatment comprising surgery followed by radiotherapy and/or stereotactic radiosurgery (n=138), whole brain radiotherapy (n=13) or stereotactic radiosurgery alone (n=102). Systemic treatment was initiated or continued after BM therapy in 169 patients and its frequency did not differ significantly between genotypes (p=.08) while the modality of medical treatment depended on genotype (p<0.0001). The latter showed longer local cerebral control rates compared to other mutations (0.23) and a longer overall survival compared to KRAS and wild type genotypes (p=.015). Systemic treatment (HR 2.1 95%CI 1.4–3.0; p<.0001) and a good clinical status (HR 2.1 95%CI 1.2–3.7; p=0.014) were the only independent factors for further survival. CONCLUSION: The actual known driver mutations do not influence BM formation. Specific genotypes show a better oncological course, presumably due to available molecular treatment.