KRASG12C Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma.

摘要: Purpose: KRASG12C is the most common KRAS mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging activity of inhibitors metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features patients with surgically resected KRASG12C-mutant Experimental Design: Patients who underwent resection stage I–III adenocarcinoma next-generation sequencing (NGS) were evaluated. Exclusion criteria receipt induction therapy, incomplete resection, low-quality NGS. Mutations classified as wild-type (KRASwt), G12C (KRASG12C), or non-G12C (KRASother). DFS was compared between groups using log-rank test; factors associated assessed Cox regression. Mutual exclusivity cooccurrence, clonality, mutational signatures assessed. Results: In total, 604 included: 374 KRASwt (62%), 95 (16%), 135 KRASother (22%). Three-year not different KRAS-mutant tumors. However, 3-year worse than tumors (log-rank P = 0.029). had more lymphovascular invasion (51% vs. 37%; 0.032) higher burden [median (interquartile range), 7.0 (5.3–10.8) 6.1 (3.5–9.7); 0.021], independently on multivariable analysis. Our findings externally validated an independent The Cancer Genome Atlas cohort. Conclusions: mutations are after complete These harbor aggressive clinicopathologic other identified a high-risk group for whom may be to improve survival.