Prediction of recurrence risk in endometrial cancer with multimodal deep learning.

Journal: Nature medicine
PMID:

Abstract

Predicting distant recurrence of endometrial cancer (EC) is crucial for personalized adjuvant treatment. The current gold standard of combined pathological and molecular profiling is costly, hampering implementation. Here we developed HECTOR (histopathology-based endometrial cancer tailored outcome risk), a multimodal deep learning prognostic model using hematoxylin and eosin-stained, whole-slide images and tumor stage as input, on 2,072 patients from eight EC cohorts including the PORTEC-1/-2/-3 randomized trials. HECTOR demonstrated C-indices in internal (n = 353) and two external (n = 160 and n = 151) test sets of 0.789, 0.828 and 0.815, respectively, outperforming the current gold standard, and identified patients with markedly different outcomes (10-year distant recurrence-free probabilities of 97.0%, 77.7% and 58.1% for HECTOR low-, intermediate- and high-risk groups, respectively, by Kaplan-Meier analysis). HECTOR also predicted adjuvant chemotherapy benefit better than current methods. Morphological and genomic feature extraction identified correlates of HECTOR risk groups, some with therapeutic potential. HECTOR improves on the current gold standard and may help delivery of personalized treatment in EC.

Authors

  • Sarah Volinsky-Fremond
    Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
  • Nanda Horeweg
    Department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands.
  • Sonali Andani
    Department of Computer Science, ETH Zurich, Zurich, Switzerland; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Jurriaan Barkey Wolf
    Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
  • Maxime W Lafarge
  • Cor D de Kroon
    Department of Gynecology and Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
  • Gitte Ørtoft
    Department of Gynecology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Estrid Høgdall
    Department of Pathology, Herlev University Hospital, Herlev, Denmark.
  • Jouke Dijkstra
    Department of Radiology, Division of Image Processing, Leiden University Medical Center, Leiden, The Netherlands.
  • Jan J Jobsen
    Department of Radiation Oncology, Medisch Spectrum Twente, Enschede, Netherlands.
  • Ludy C H W Lutgens
    Department of Radiation Oncology, Maastricht University Medical Center+, Maastricht, Netherlands.
  • Melanie E Powell
    Department of Clinical Oncology, Barts Health NHS Trust, London, UK.
  • Linda R Mileshkin
    Department of Medical Oncology, Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
  • Helen Mackay
    Department of Medical Oncology and Hematology, Odette Cancer Center Sunnybrook Health Sciences Center, Toronto, Ontario, Canada.
  • Alexandra Leary
    Medical Oncology Department, Gustave Roussy Institute, Villejuif, France.
  • Dionyssios Katsaros
    Department of Surgical Sciences, Gynecologic Oncology, Città della Salute and S Anna Hospital, University of Turin, Turin, Italy.
  • Hans W Nijman
    Department of Obstetrics and Gynecology, University Medical Center Groningen, Groningen, Netherlands.
  • Stephanie M de Boer
    Department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands.
  • Remi A Nout
    Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Marco de Bruyn
    Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • David Church
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Vincent T H B M Smit
    Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
  • Carien L Creutzberg
    Department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands.
  • Viktor H Koelzer
    Institute of Cancer and Genomic Science, University of Birmingham, 6 Mindelsohn Way, Birmingham, B15 2SY, UK. vkoelzer@well.ox.ac.uk.
  • Tjalling Bosse
    Department of Pathology, Leiden University Medical Center, Leiden, Netherlands. Electronic address: t.bosse@lumc.nl.