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Intrahepatic Cholangiocarcinoma: Recurrence Patterns, Genomics, and Survival.

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Recurrence after intrahepatic cholangiocarcinoma (IHC) resection is common. Simultaneous liver and extrahepatic recurrence portends worse survival than liver-only or extrahepatic-only recurrence, suggesting targeted adjuvant therapies may improve outcomes.

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Area of Science:

  • Oncology
  • Surgical Oncology
  • Genomics

Background:

  • Intrahepatic cholangiocarcinoma (IHC) recurrence patterns and genomic drivers remain incompletely understood.
  • The impact of the first recurrence site on patient outcomes after surgical resection is not well-defined.

Purpose of the Study:

  • To investigate the impact of the first recurrence site on overall survival (OS) after intrahepatic cholangiocarcinoma (IHC) resection.
  • To explore the genomic underpinnings associated with recurrence patterns and outcomes in resected IHC.

Main Methods:

  • Retrospective analysis of 318 patients with resected IHC from two institutions with available genomic data.
  • Classification of first recurrence sites into liver only (LO), extrahepatic (EH) only, or simultaneous liver and extrahepatic (SIM).
  • Calculation of overall survival (OS) from the time of recurrence and correlation with clinicopathologic and genomic factors.

Main Results:

  • Of 232 patients who recurred, sites were LO (40%), EH (34%), and SIM (26%).
  • Median OS from recurrence was significantly lower for SIM (12 months) compared to LO (33 months) and EH (33 months) (P < .001).
  • TP53 mutations, CDKN2A deletions, CDKN2B deletions, and KRAS mutations were associated with worse OS; SIM recurrence, N1 status, and a high-risk genotype independently predicted poor OS.

Conclusions:

  • Simultaneous liver and extrahepatic recurrence is associated with dramatically worse survival after IHC resection.
  • Clinicopathologic and genomic factors showed limited ability to predict the site of first recurrence.
  • Adjuvant strategies targeting liver recurrence may be beneficial for improving outcomes in resected IHC patients.