Evaluating the Prognostic Impact of IDH Mutations in Intrahepatic Cholangiocarcinoma

作者：Rachel Harvey, Rebecca Gelfer, Esther Drill, Vinod P. Balachandran, Michael D'Angelica, Jeffrey A. Drebin, T.P. Kingham, Lily Saadat, Kevin C. Soares, Alice C. Wei, Ghassan K. Abou‐Alfa, Andrea Cercek, James J. Harding, Eileen M. O’Reilly, Michail Doukas, Marjolein Y.V. Homs, Bas Groot Koerkamp, William R. Jarnagin · 发表于：JCO Precision Oncology · 年份：2026 · DOI：10.1200/po-25-01261 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Gallbladder and Bile Duct Disorders、Hepatocellular Carcinoma Treatment and Prognosis

PURPOSE Isocitrate dehydrogenase 1 and 2 ( IDH1 and IDH2 ) mutations are common in intrahepatic cholangiocarcinoma (ICC), but their prognostic value is unclear. Using a large data set, we assessed their impact in resected and nonresected ICC. METHODS Adults from two medical centers (MSKCC and Erasmus) with ICC treated with curative-intent resection (resected) or managed nonoperatively (unresectable) who underwent next-generation sequencing were analyzed retrospectively. Kaplan-Meier and Cox regressions assessed the impact of IDH status on outcomes. RESULTS Of the 795 patients analyzed, 25% had IDH1/2 mutations ( IDH mut) and 43% underwent resection. Median overall survival (OS) of the cohort was 32 months in IDH mut and 28 months for IDH wt ( P = .2). High-risk genetic alterations ( TP53 mut, KRAS mut, and CDKN2A del) were more frequent in IDH wild-type ( IDH wt; odds ratio, 2.26; q < 0.001). OS was 19 months in patients with high-risk alterations versus 40 months in patients without ( P < .001). In resected patients, recurrence-free survival (RFS) in IDH mut was 20 months versus 14 months for IDH wt ( P = .018), and OS was 69 months versus 50 months, respectively ( P = .2). However, after controlling for high-risk alterations, the potential benefit of IDH mut was no longer apparent (RFS: hazard ratio [HR], 0.78; P = .095; OS: HR, 0.88; P = .4). In unresectable IDH mut patients, progression-free survival was 9.4 months versus 9.1 months for IDH wt ( P = .7), and OS was ...