Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma - PubMed (original) (raw)

. 2015 Sep;20(9):1019-27.

doi: 10.1634/theoncologist.2015-0210. Epub 2015 Aug 5.

Aparna Govindan 1, Rahul A Sheth 1, Valentina Nardi 1, Lawrence S Blaszkowsky 1, Jason E Faris 1, Jeffrey W Clark 1, David P Ryan 1, Eunice L Kwak 1, Jill N Allen 1, Janet E Murphy 1, Supriya K Saha 1, Theodore S Hong 1, Jennifer Y Wo 1, Cristina R Ferrone 1, Kenneth K Tanabe 1, Dawn Q Chong 1, Vikram Deshpande 1, Darrell R Borger 1, A John Iafrate 1, Nabeel Bardeesy 1, Hui Zheng 1, Andrew X Zhu 2

Affiliations

Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma

Lipika Goyal et al. Oncologist. 2015 Sep.

Abstract

Background: Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC.

Methods: Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging.

Results: Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status.

Conclusion: The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation.

Implications for practice: Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with unresectable or metastatic disease, and the current study is the first to focus on the prognosis and clinical phenotype of this population and reports on the largest cohort of patients with advanced IDH mutant ICC to date. The finding that the IDH mutation lacks prognostic significance in advanced ICC is preliminary and needs to be confirmed prospectively in a larger study.

Keywords: Cholangiocarcinoma; Isocitrate dehydrogenase; Metastatic; Phenotype; Prognosis.

©AlphaMed Press.

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Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1.

Figure 1.

Comparison of CA19-9 in pateints with IDH_m_ versus IDH_wt_ advanced intrahepatic cholangiocarcinoma (ICC). (A): Comparison of the log10 pretreatment CA19-9 level in patients with IDH_m_ versus IDH_wt_ advanced ICC. The median log10 pretreatment CA19-9 level for patients with IDH_m_ versus IDH_wt_ disease was 1.42 and 1.96, respectively (p = .04). (B): Comparison of the log10 pretreatment CA19-9 to tumor volume ratio in patients with IDH_m_ versus IDH_wt_ advanced ICC. The median log10 pretreatment CA19-9 to tumor volume ratio for patients with IDH_m_ versus IDH_wt_ disease was −0.30 and 0.14, respectively. Abbreviations: CA19-9, carbohydrate antigen 19-9; IDH_m_, isocitrate dehydrogenase mutant; IDH_wt_, isocitrate dehydrogenase wild type.

Figure 2.

Figure 2.

Tumor volume (TV) assessment based on abdominal computed tomography scans. Frontal projections of three-dimensional reconstructions demonstrate liver tumor volumes (green) overlaid on anatomic structures in two patients. Reconstructions and semiautomatic tumor volume calculations were generated by a commercial software package (iNtuition). (A): Computed tomography scan of a 47-year-old white man with primary, unresectable isocitrate dehydrogenase (IDH) wild-type intrahepatic cholangiocarcinoma (ICC) with a baseline carbohydrate antigen 19-9 (CA19-9) level of 5,688 U/mL and a baseline TV of 1,487 cm3. (B): Computed tomography scan a 59-year-old white woman with primary, unresectable IDH-mutant ICC with a baseline CA19-9 level of 24 U/mL and TV of 1,007 cm3.

Figure 3.

Figure 3.

Overall survival of patients with isocitrate dehydrogenase (IDH) mutant (IDH_m_) versus IDH wild-type (IDH_wt_) unresectable or metastatic intrahepatic cholangiocarcinoma since date of diagnosis of advanced disease. The median overall survival of patients with IDH_m_ versus IDH_wt_ advanced-stage disease was 15.0 months versus 20.1 months, respectively (p = .17).

References

    1. Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24:115–125. - PubMed
    1. Park I, Lee JL, Ryu MH, et al. Prognostic factors and predictive model in patients with advanced biliary tract adenocarcinoma receiving first-line palliative chemotherapy. Cancer. 2009;115:4148–4155. - PubMed
    1. Walter T, Horgan AM, McNamara M, et al. Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: A large retrospective study. Eur J Cancer. 2013;49:329–335. - PubMed
    1. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–1281. - PubMed
    1. Kipp BR, Voss JS, Kerr SE, et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Hum Pathol. 2012;43:1552–1558. - PubMed

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