Nerve Fibers in the Tumor Microenvironment as a Novel Biomarker for Oncological Outcome in Patients Undergoing Surgery for Perihilar Cholangiocarcinoma

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jan Bednarsch - , University Hospital Aachen (Author)
  • Jakob Kather - , Else Kröner Fresenius Center for Digital Health, University Hospital Aachen (Author)
  • Xiuxiang Tan - , University Hospital Aachen (Author)
  • Shivan Sivakumar - , University of Oxford (Author)
  • Claudio Cacchi - , University Hospital Aachen (Author)
  • Georg Wiltberger - , University Hospital Aachen (Author)
  • Zoltan Czigany - , University Hospital Aachen (Author)
  • Florian Ulmer - , University Hospital Aachen (Author)
  • Ulf Peter Neumann - , University Hospital Aachen (Author)
  • Lara Rosaline Heij - , University Hospital Aachen (Author)

Abstract

INTRODUCTION: Perihilar cholangiocarcinoma (pCCA) is a biliary tract cancer with a dismal prognosis, with surgery being the only chance of cure. A characteristic aggressive biological feature of pCCA is perineural growth which is defined by the invasion of cancer cells to nerves and nerve fibers. Recently, nerve fiber density (NFD) was linked to oncological outcomes in various malignancies; however, its prognostic role in pCCA remains to be elucidated.

MATERIALS AND METHODS: Data of 101 pCCA patients who underwent curative-intent surgery between 2010 and 2019 were included in this study. Extensive group comparisons between patients with high and low NFD were carried out, and the association of cancer-specific survival (CSS) and recurrence-free survival with NFD and other clinicopathological characteristics was assessed using univariate and multivariable cox regression models.

RESULTS: Patients with high NFD showed a median CSS of 90 months (95% CI: 48-132, 3-year CSS = 77%, 5-year CSS = 72%) compared to 33 months (95% CI: 19-47, 3-year CSS = 46%, 5-year CSS = 32%) in patients with low NFD ( p = 0.006 log rank). Further, N1 category (HR = 2.84, p = 0.001) and high NFD (HR = 0.41, p = 0.024) were identified as independent predictors of CSS in multivariable analysis. Patients with high NFD and negative lymph nodes showed a median CSS of 90 months (3-year CSS = 88%, 5-year CSS = 80%), while patients with either positive lymph nodes or low NFD displayed a median CSS of 51 months (3-year CSS = 59%, 5-year CSS = 45%) and patients with both positive lymph nodes and low NFD a median CSS of 24 months (3-year CSS = 26%, 5-year CSS = 16%, p = 0.001 log rank).

CONCLUSION: NFD has been identified as an important novel prognostic biomarker in pCCA patients. NFD alone and in combination with nodal status in particular allows to stratify pCCA patients based on their risk for inferior oncological outcomes after curative-intent surgery.

Details

Original languageEnglish
Pages (from-to)260-274
Number of pages15
JournalLiver cancer
Volume10
Issue number3
Publication statusPublished - Jun 2021
Peer-reviewedYes

External IDs

PubMedCentral PMC8237795
Scopus 85107488773

Keywords

Sustainable Development Goals

Library keywords