DOI: 10.1200/po-25-01261 ISSN: 2473-4284
Evaluating the Prognostic Impact of IDH Mutations in Intrahepatic Cholangiocarcinoma
Rachel N. Harvey, Rebecca Gelfer, Esther Drill, Vinod Balachandran, Michael D'Angelica, Jeffrey Drebin, T Peter Kingham, Lily Saadat, Kevin 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
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 22 months versus 18 months, respectively (
P
= .13). There remained no differences after controlling for high-risk alterations.
IDH
status was not a significant survival predictor in multivariable models.
CONCLUSION
In this cohort of patients with ICC,
IDH
mut was not an independent predictor of survival, after controlling for high-risk alterations and clinical variables.
IDH
mutational status alone should, therefore, not be used to guide prognosis.