Evaluating the Prognostic Impact of IDH Mutations in Intrahepatic Cholangiocarcinoma.
Source: PubMed, NCBI / U.S. National Library of Medicine
Isocitrate dehydrogenase 1 and 2 (and) 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. 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. Of the 795 patients analyzed, 25% hadmutations (mut) and 43% underwent resection. Median overall survival (OS) of the cohort was 32 months inmut and 28 months forwt (= .2). High-risk genetic alterations (mut,mut, anddel) were more frequent inwild-type (wt; odds ratio, 2.26; q < 0.001). OS was 19 months in patients with high-risk alterations versus 40 months in patients without (< .001). In resected patients, recurrence-free survival (RFS) inmut was 20 months versus 14 months forwt (= .018), and OS was 69 months versus 50 months, respectively (= .2). However, after controlling for high-risk alterations, the potential benefit ofmut was no longer apparent (RFS: hazard ratio [HR], 0.78;= .095; OS: HR, 0.88;= .4). In unresectablemut patients, progression-free survival was 9.4 months versus 9.1 months forwt (= .7), and OS was 22 months versus 18 months, respectively (= .13). There remained no differences after controlling for high-risk alterations.status was not a
Abstract
Isocitrate dehydrogenase 1 and 2 (and) 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. 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. Of the 795 patients analyzed, 25% hadmutations (mut) and 43% underwent resection. Median overall survival (OS) of the cohort was 32 months inmut and 28 months forwt (= .2). High-risk genetic alterations (mut,mut, anddel) were more frequent inwild-type (wt; odds ratio, 2.26; q < 0.001). OS was 19 months in patients with high-risk alterations versus 40 months in patients without (< .001). In resected patients, recurrence-free survival (RFS) inmut was 20 months versus 14 months forwt (= .018), and OS was 69 months versus 50 months, respectively (= .2). However, after controlling for high-risk alterations, the potential benefit ofmut was no longer apparent (RFS: hazard ratio [HR], 0.78;= .095; OS: HR, 0.88;= .4). In unresectablemut patients, progression-free survival was 9.4 months versus 9.1 months forwt (= .7), and OS was 22 months versus 18 months, respectively (= .13). There remained no differences after controlling for high-risk alterations.status was not a significant survival predictor in multivariable models. In this cohort of patients with ICC,mut was not an independent predictor of survival, after controlling for high-risk alterations and clinical variables.mutational status alone should, therefore, not be used to guide prognosis.