Association of IDH1 Mutations with Survival and Recurrence in Resected Intrahepatic Cholangiocarcinoma Received or not Received Adjuvant Chemotherapy

Abstract Background IDH1 mutations are causal in tumor development and progression; however, their association with disease characteristics, prognosis, and therapy response in patients with resected intrahepatic cholangiocarcinoma (ICC) remains controversial. Materials and Methods In this cohort study, we recruited 803 patients who underwent curative resection for ICC at a single hospital in China. We performed whole-exome sequencing and Sanger sequencing to identify IDH1 mutations. We used the Kaplan–Meier method and log-rank test to compare overall survival (OS) and disease-free survival (DFS). Results A total of five different subtypes of IDH1 somatic mutation affecting 94 (11.7%) patients were identified. R132C was the most frequent mutant allele in this cohort, followed by R132L and R132G. Across all patients considered, those that received adjuvant chemotherapy had significantly superior OS and DFS compared with those that did not receive adjuvant chemotherapy. In the whole ICC cohort, patients with IDH1 mutations showed no significant difference in OS compared with patients with wild-type IDH1. When we looked at patients that either received or did not receive adjuvant chemotherapy separately, univariate and multivariable analyses revealed that IDH1 mutations were significantly associated with superior OS among patients that received adjuvant chemotherapy, whereas they were marginally associated with worse OS among patients that did not receive adjuvant chemotherapy. Conclusion We characterized the distribution of IDH1 mutations in a large cohort of patients with ICC from China. The presence of IDH1 mutations was associated with better survival and decreased risk of recurrence in patients with resected ICC that received adjuvant chemotherapy.