Adjuvant Hepatic Artery Infusion Chemotherapy is Associated With Improved Survival Regardless of KRAS Mutation Status in Patients With Resected Colorectal Liver Metastases

Abstract

OBJECTIVE:To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). BACKGROUND:Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. METHODS:Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. RESULTS:Between 1993-2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group, however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI vs 57% for patients without HAI (HR 0.51, p<0.001). In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI vs. 40% for patients without HAI (HR 0.56, p<0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, p<0.002) independent of KRAS status and other clinico-pathologic factors.

Reevaluating the prognostic value of RAS mutation status in patients with resected liver metastases from colorectal cancer: A systematic review and meta‐analysis

“…Of the 10 studies that included patients who underwent liver resection, eight were retrospective cohort studies 6,8,9,12‐16 and two were prospectively maintained databases 10,17 . In total, 3491 patients were incorporated, of which 3115 had known RAS status (1123 with mutated RAS vs 1992 with wild‐type RAS).…”

“…Seven studies 6,8‐10,15‐17 reported data regarding the OS of 2779 patients with known RAS status. Patients with RAS gene mutations were found to have significantly worse OS rates (HR 1.49, 95% CI 1.3‐1.71, P < .001; Figure 2).…”

“…Data relating to disease‐free survival were available in seven studies, 6,8,10,12‐14,17 totaling 2644 patients with known RAS status. Pooled results revealed that patients harboring the RAS mutation had worse DFS than their wild‐type counterparts (HR 1.36, 95% CI 1.22‐1.51, P < .001; Figure 3).…”

Recurrence After Liver Resection of Colorectal Liver Metastases: Repeat Resection or Ablation Followed by Hepatic Arterial Infusion Pump Chemotherapy

“…However, previous studies have demonstrated that the effect of HAIP chemotherapy is independent of KRAS mutational studies. 18 Other studies demonstrated that RAS mutations are associated with unsalvageable recurrences after initial hepatectomy; this may also apply for subsequent recurrences after curative treatment of recurrent CRLM. 19 However, primary tumor location, which is associated with KRAS mutations, and inferior survival in right-sided patients in previous studies, were included in multivariable analysis in this paper.…”

Unravel hepatic artery infusion chemotherapy in patients with resected colorectal liver metastases

“…On this line, we read with interest the retrospective study published by Gholami et al (5), who recently reported on the utilization of adjuvant HAI in the setting of resected CLM. In particular, they reported how adjuvant HAI was independently associated with improved recurrencefree and overall survival regardless of KRAS mutational status.…”