Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug;149(9):6391-6398.
doi: 10.1007/s00432-023-04603-7. Epub 2023 Feb 9.

Impact of IDH1 mutation on clinical course of patients with intrahepatic cholangiocarcinoma: a retrospective analysis from a German tertiary center

Maximilian N Kinzler  1 , Jan Jeroch  2 , Christina Klasen  1 , Vera Himmelsbach  1 , Christine Koch  1 , Fabian Finkelmeier  1 , Jörg Trojan  1 , Stefan Zeuzem  1 , Ursula Pession  3 , Henning Reis  2 , Melanie C Demes  2 , Peter J Wild  2   4   5 , Dirk Walter  6
Affiliations

Impact of IDH1 mutation on clinical course of patients with intrahepatic cholangiocarcinoma: a retrospective analysis from a German tertiary center

Maximilian N Kinzler et al. J Cancer Res Clin Oncol. 2023 Aug.

Abstract

Purpose: IDH1 mutation is a known biomarker for targeted therapy of intrahepatic cholangiocarcinoma (iCCA), while its prognostic relevance for current palliative chemotherapy is still unclear. Aim of this study was to analyze clinicopathological characteristics of patients with IDH1 mutations and to outline a potential impact on the outcome after state-of-the-art palliative chemotherapy regimens.

Methods: All patients with iCCA receiving large panel molecular profiling and follow-up treatment at Frankfurt University Hospital until 04/2022 were retrospectively analyzed. Clinicopathological characteristics were assessed for IDH1 mutated (mut) and IDH1 wild type (wt) patients, and progression-free survival (PFS) and overall survival (OS) were determined.

Results: In total, 75 patients with iCCA received molecular profiling. Of the patients with available DNA data, pathogenic mutations in IDH1 were found in 14.5% (n = 10). IDH1 mut status was associated with lower serum CA-19/9 (p = 0.023), lower serum lactate dehydrogenase (p = 0.006), and a higher proportion of primary resectability (p = 0.028) as well as response to chemotherapy after recurrence (p = 0.009). Median PFS was 5.9 months (95% CI 4.4-7.3 months) for IDH1 wt in comparison to 9.8 months (95% CI 7.7-12 months) for patients with IDH1 mut (p = 0.031). IDH1 wt was a significant risk factor for shortened PFS in univariate (p = 0.043), but not in multivariate analysis (p = 0.061). There was no difference in OS between both groups.

Conclusion: Patients with IDH1 mutated iCCA seem to have a favorable tumor biology including a longer PFS for palliative chemotherapy regimens compared to IDH1 wild type.

Keywords: Chemotherapy; Intrahepatic cholangiocarcinoma; Isocitrate dehydrogenase 1; Progression-free survival.

PubMed Disclaimer

Conflict of interest statement

C. K. reports consulting fees, speaker fees, or travel support from Eisai, Elsevier, Ipsen, Medac, Merck, MSD, Novartis, Roche, Bayer, BMS, Astra Zeneca and Servier. F. F. has received travel support from Ipsen, and speaker fees from AbbVie, MSD, Ipsen, Eisai and Fresenius. J.T. received honoraria for consulting and advisory board role from Amgen, Astra Zeneca, Bayer Healthcare, Bristol Myers-Squibb, Eisai, Ipsen, Merck Serono, Merck Sharp & Dome, Lilly Imclone, Roche and Servier; research support was provided by Ipsen and Roche. S.Z. has received speaker fees and/or honoraria for consultancy from AbbVie, Allergan, BioMarin, Gilead, Intercept, Janssen, MSD/Merck, NovoNordisk, SoBi and Theratechnologies. H.R. was on an advisory board of Bristol-Myers Squibb, received honoraria from Roche, Bristol-Myers Squibb, Janssen-Cilag GmbH, Novartis and Astra Zeneca, received travel support from Philips, Roche, and Bristol-Myers Squibb, received grants from Bristol-Myers Squibb and holds shares of Bayer. P.J.W. has received consulting fees and honoraria for lectures by Bayer, Janssen-Cilag, Novartis, Roche, MSD, Astellas Pharma, Bristol-Myers Squibb, Thermo Fisher Scientific, Molecular Health, Guardant Health, Sophia Genetics, Qiagen, Eli Lilly, Myriad, Hedera Dx, and Astra Zeneca; research support was provided by Astra Zeneca. All other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves for progression-free and overall survival in patients with iCCA. a/b Progression-free survival a and overall survival b in IDH1 (mut) / (wt) patients with iCCA receiving palliative chemotherapy. Date of last follow-up was treated as censored observation. One patient who was molecularly profiled as part of research projects was excluded from the analysis of overall survival in the palliative setting as no recurrence occurred in this patient after surgical resection with curative intent. iCCA intrahepatic cholangiocarcinoma, IDH1 isocitrate dehydrogenase 1
See this image and copyright information in PMC

References

    1. Abou-Alfa GK, Macarulla T, Javle MM et al (2020) Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 21:796–807. 10.1016/S1470-2045(20)30157-1 - PMC - PubMed
    1. Borger DR, Tanabe KK, Fan KC et al (2012) Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 17:72–79. 10.1634/theoncologist.2011-0386 - PMC - PubMed
    1. Boscoe AN, Rolland C, Kelley RK (2019) Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review. J Gastrointest Oncol 10:751–765. 10.21037/jgo.2019.03.10 - PMC - PubMed
    1. Churi CR, Shroff R, Wang Y et al (2014) Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS ONE 9:e115383. 10.1371/journal.pone.0115383 - PMC - PubMed
    1. Dong LQ, Shi Y, Ma LJ et al (2018) Spatial and temporal clonal evolution of intrahepatic cholangiocarcinoma. J Hepatol 69:89–98. 10.1016/j.jhep.2018.02.029 - PubMed

Substances

LinkOut - more resources