Benchmarking outcomes after ablative radiotherapy for molecularly characterized intrahepatic cholangiocarcinoma

Brian De, Ibrahim Abu-Gheida, Aashini Patel, Sylvia S.W. Ng, Mohamed Zaid, Connor P. Thunshelle, Dalia Elganainy, Kelsey L. Corrigan, Michael K. Rooney, Milind Javle, Kanwal Raghav, Sunyoung S. Lee, Jean Nicolas Vauthey, Ching Wei D. Tzeng, Hop S.Tran Cao, Ethan B. Ludmir, Bruce D. Minsky, Grace L. Smith, Emma B. Holliday, Cullen M. TaniguchiAlbert C. Koong, Prajnan Das, Eugene J. Koay

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2–18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81–144 Gy). The median (95% confidence interval) follow-up was 58 (42–104) months from diagnosis and 39 (33–74) months from RT. The median OS was 32 (29–35) months after diagnosis and 20 (16–24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65–80%), 81% (73–87%), and 34% (26–42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.

Original languageEnglish (US)
Article number1270
JournalJournal of Personalized Medicine
Volume11
Issue number12
DOIs
StatePublished - Dec 2021

Keywords

  • Cholangiocarcinoma
  • Genetic
  • Genomic
  • Mutation
  • Radiotherapy

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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