title: Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lipika
authors.initials: L
authors.lastname: Goyal
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Govindan
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rahul A
authors.initials: RA
authors.lastname: Sheth
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nardi
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Faris
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jill N
authors.initials: JN
authors.lastname: Allen
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Murphy
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Supriya K
authors.initials: SK
authors.lastname: Saha
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Wo
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Tanabe
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dawn Q
authors.initials: DQ
authors.lastname: Chong
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Borger
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Bardeesy
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA azhu@partners.org.
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase
keywords: Cholangiocarcinoma; Isocitrate dehydrogenase; Metastatic; Phenotype; Prognosis