86P - KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma

Background

KRAS G12C mutations are found in about 12–13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, early stage LUAD. We evaluated a retrospective, single-center cohort of patients treated with video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracoscopic surgery (RATS) at our institution and leveraged on publicly available cohorts (TCGA LUAD, MSK LUAD⁶⁰⁴) to confirm the findings.

Methods

IRE cohort: retrospective cohort of patients with surgically resected, pathological stage I LUAD whose tumor tissue underwent targeted sequencing. TCGA LUAD cohort: pathologic stage I LUAD; patients who received post-operative radiation therapy and patients exposed to non-curative surgical resection were not included. MSK LUAD⁶⁰⁴ cohort: pathologic stage I LUAD. Clinical and genomic data for the TCGA LUAD and MSK LUAD⁶⁰⁴ cohort were downloaded from cBioPortal. The pooled cohort was made up by merging eligible patients in the IRE stage I cohort, TCGA LUAD stage I cohort and MSK LUAD604 stage I cohort.

Results

In the IRE stage I cohort we found a significant association between KRAS G12C mutations and worse DFS in multivariate analysis (DFS HR 2.47). In the TCGA LUAD stage I cohort we did not find any statistically significant association between the KRAS G12C mutation and survival outcomes. In the MSK LUAD604 stage I cohort we found that KRAS G12C mutated tumors had worse survival outcomes only when compared to KRAS nonG12C mutated tumors in univariate analysis (DFS HR 3.5). In the pooled stage I cohort (IRE stage I, TCGA LUAD stage I and MSK LUAD604 stage I tumors) we found that KRAS G12C mutated tumors had worse DFS when compared to KRAS nonG12C mutated tumors (DFS HR 2.6), to KRAS wild type tumors (DFS HR 1.6) and to any other tumors (DFS HR 1.8) in univariate analysis; in multivariable analysis, the KRAS G12C mutation was associated with worse DFS (DFS HR 1.61).

Conclusions

Our results suggest that patients with resected, stage I LUAD with a KRAS G12C mutation may have inferior survival outcomes when compared to KRAS nonG12C mutated tumors and to KRAS wild type tumors.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.