Locl-05 cerebral metastatic lung carcinoma: effect of alk- and egfr-mutation status and surgical management upon clinical outcome

Abstract PURPOSE There have been many advancements in the surgical and medical treatment of metastatic lung carcinoma. In the post-genomic era, new directed-oncological therapies such as monoclonal antibodies (mAbs) and tyrosine-kinase inhibitors (TKIs) may offer increased survival for lung carcinoma patients with EGFR- and ALK- mutations. No surgical series have investigated the role of these mutations upon patient survival in lung brain metastases (BM). METHODS We performed a multi-site, retrospective study of all patients who had BM with primary lung cancer undergoing surgical resection at Emory University Hospital between January 2012 and March 2021. Driver mutational statuses were categorized as EGFR-amplified, ALK-rearranged, or wild-type from biopsied brain tissue. Descriptive, univariate, and multivariate survival analyses were performed. RESULTS 95 patients (mean age: 65.8 ± 10.6) met the inclusion criteria. 6 (6.3%) had ALK-rearranged mutations and 19 (20.0%) had EGFR-amplified mutations. 9 (9.5%) received second line therapies in the form of TKIs and mAbs. The majority of patients who underwent craniotomies had gross total resection (GTR) (n=72, 79.1%) with 83.5% (95% CI: 71.2-90.8%) and 89.9% (95% CI: 74.9-96.2%) 1-year overall survival (OS) and progression-free survival (PFS), respectively. On univariate analysis, ALK-rearranged (HR: 2.92; 95% CI: 0.57-9.75; p-value = 0.230) and EGFR-amplified (HR: 0.56; 95% CI: 0.15-1.61; p-value = 0.260) mutations were not significantly associated with OS. CONCLUSION After assessing ALK- and EGFR- mutations on OS, we found no benefit with mutational status, unlike other cancer types such as Melanoma BRAF mutations. Our low sample size of patients receiving targeted therapies may bias our measures of association to the null hypothesis. However, the OS and PFS in our cohort were better than earlier trials in literature, demonstrating the improvement in systemic lung metastasis therapy. We suspect that as further targeted therapies become available, OS and PFS for lung BM patients will continue to improve.