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PPS47. Evaluating the Prognostic Impact of IDH Mutations in Intrahepatic Cholangiocarcinoma

Friday, March 6, 2026
3:40 PM - 4:10 PM MST
Location: HUB Poster Park - West Hall 1-3
Introduction

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1, IDH2) are common in intrahepatic cholangiocarcinoma (ICC), but their prognostic value is unclear. Using a large, clinically annotated dataset, we assessed their impact in resected and non-resected ICC.

Methods

This was a retrospective study of ICC patients who underwent next-generation sequencing from 2008-2022. Adults treated with curative intent resection (resected) or managed nonoperatively (unresectable) were analyzed.

Results

Of 795 patients, 25% had IDH1/2 mutations (80% IDH1, 20% IDH2) (IDHmut) and 43% underwent resection. High-risk genetic alterations (TP53mut, KRASmut, CDKN2Adel) were more frequent in IDH wild-type (IDHwt) (IDHmut, OR 2.26; q<0.001) (Table 1). In the entire cohort, median overall survival (OS) was 32 months in IDHmut and 28 months for IDHwt (p=0.2); by contrast, OS was 19 months in patients with high-risk alterations compared to 40 months without (p<0.001). In resected patients, recurrence free survival (RFS) in IDHmut was 20 months vs. 14 months for IDHwt (p=0.018), and OS was 69 months vs. 50 months, respectively (p=0.2); however, after controlling for high-risk genetic alterations, any benefit of IDHmut disappeared (RFS: HR 0.78; p=0.095; OS: HR 0.88; p=0.4). In unresectable patients, progression free survival (PFS) in IDHmut was 9.4 months compared to 9.1 months for IDHwt (p=0.7), and OS was 22 months vs. 18 months, respectively (p=0.13). There remained no significant differences after controlling for high-risk alterations (PFS: HR 1.03; p=0.8; OS: HR 0.94; p=0.6). IDH mutational status was not a significant survival predictor in multivariable models for both resected and non-resected patients. In 42 patients with unresectable IDHmut treated with IDH inhibitors, median OS was 12 months.

Conclusions

In this large cohort of resected and non-resected ICC patients, IDH mutations were not an independent predictor of survival after controlling for high-risk genetic alterations and clinical variables. Thus, IDH status should not be used in isolation to guide prognosis.

Learning Objectives:

  • IDH mutations in intrahepatic cholangiocarcinoma are not independent predictors of survival. Therefore, IDH status alone should not be used to guide prognostication.
  • Co-occurring high risk genetic alterations in KRAS and TP53 and CDK2NAdel may confer worse survival outcomes.