(HPB P4) Clinical Significance of SMAD4 Mutation Status in Patients with Resected Colorectal Liver Metastases

In patients (pts) with colorectal liver metastases (CRLM), SMAD4 mutations have been associated with worse survival. The impact of SMAD4 mutation status in pts undergoing hepatectomy and adjuvant hepatic arterial chemotherapy (A-HAIC) is unknown. Pts with SMAD4 mutation status (wild type, WT; mutated, MUT) undergoing hepatectomy between 2001-2017 were identified from an institutional database. Overall survival (OS) and disease-free survival (DFS) from hepatectomy were estimated using Kaplan-Meier methods and compared between subgroups using log-rank test and Cox regression. 329 pts were included. Median follow-up amongst survivors was 46 months. 13% were SMAD4 MUT, 74% received chemotherapy before hepatectomy, 83% received adjuvant systemic, 58% received A-HAIC. SMAD4 MUT was not associated with OS (5 years OS MUT 60% vs. WT 67%, p=0.306) or DFS (5 years DFS MUT 38% vs. WT 27%, p=0.090). A-HAIC was associated with improved OS (5year OS A-HAIC 71% vs. No A-HAIC 58%, p=0.01) and DFS (5year DFS A-HAIC 40% vs. No A-HAIC 11%, p<0.001). On multivariable analysis, A-HAIC was associated with improved OS (A-HAIC HR=0.60, 95% CI 0.38-0.898, p= 0.014) and DFS (A-HAIC HR 0.5, 95% CI 0.378-0.646, p<0.001) regardless of SMAD4 status. While Clinical Risk Score was associated with OS and DFS, SMAD4 mutation status was not prognostic. In pts with CRLM undergoing hepatectomy, SMAD4 status is not associated with OS or DFS. In the setting of A-HAIC, SMAD4 mutation status may not carry prognostic significance.