Deep learning can predict survival directly from histology in clear cell renal cell carcinoma.

Journal: PloS one
Published Date:

Abstract

For clear cell renal cell carcinoma (ccRCC) risk-dependent diagnostic and therapeutic algorithms are routinely implemented in clinical practice. Artificial intelligence-based image analysis has the potential to improve outcome prediction and thereby risk stratification. Thus, we investigated whether a convolutional neural network (CNN) can extract relevant image features from a representative hematoxylin and eosin-stained slide to predict 5-year overall survival (5y-OS) in ccRCC. The CNN was trained to predict 5y-OS in a binary manner using slides from TCGA and validated using an independent in-house cohort. Multivariable logistic regression was used to combine of the CNNs prediction and clinicopathological parameters. A mean balanced accuracy of 72.0% (standard deviation [SD] = 7.9%), sensitivity of 72.4% (SD = 10.6%), specificity of 71.7% (SD = 11.9%) and area under receiver operating characteristics curve (AUROC) of 0.75 (SD = 0.07) was achieved on the TCGA training set (n = 254 patients / WSIs) using 10-fold cross-validation. On the external validation cohort (n = 99 patients / WSIs), mean accuracy, sensitivity, specificity and AUROC were 65.5% (95%-confidence interval [CI]: 62.9-68.1%), 86.2% (95%-CI: 81.8-90.5%), 44.9% (95%-CI: 40.2-49.6%), and 0.70 (95%-CI: 0.69-0.71). A multivariable model including age, tumor stage and metastasis yielded an AUROC of 0.75 on the TCGA cohort. The inclusion of the CNN-based classification (Odds ratio = 4.86, 95%-CI: 2.70-8.75, p < 0.01) raised the AUROC to 0.81. On the validation cohort, both models showed an AUROC of 0.88. In univariable Cox regression, the CNN showed a hazard ratio of 3.69 (95%-CI: 2.60-5.23, p < 0.01) on TCGA and 2.13 (95%-CI: 0.92-4.94, p = 0.08) on external validation. The results demonstrate that the CNN's image-based prediction of survival is promising and thus this widely applicable technique should be further investigated with the aim of improving existing risk stratification in ccRCC.

Authors

  • Frederik Wessels
    Digital Biomarkers for Oncology Group, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Max Schmitt
    National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany.
  • Eva Krieghoff-Henning
    Digital Biomarkers for Oncology Group (DBO), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Jakob N Kather
    Department of Gastroenterology, University Hospital RWTH Aachen, Aachen, Germany. jakob.kather@gmail.com.
  • Malin Nientiedt
    Department of Urology & Urological Surgery, Medical Faculty Mannheim of Heidelberg University, University Medical Center Mannheim, Mannheim, Germany.
  • Maximilian C Kriegmair
    Department of Urology, University Medical Centre Mannheim, Mannheim, Germany. Maximilian.Kriegmair@medma.uni-heidelberg.de.
  • Thomas S Worst
    Department of Urology and Urological Surgery, Medical Faculty Mannheim of Heidelberg University, University Medical Center Mannheim, Mannheim, Germany.
  • Manuel Neuberger
    Department of Urology and Urological Surgery, Medical Faculty Mannheim of Heidelberg University, University Medical Center Mannheim, Mannheim, Germany.
  • Matthias Steeg
    Institute of Pathology, Medical Faculty Mannheim of Heidelberg University, University Medical Center Mannheim, Mannheim, Germany.
  • Zoran V Popovic
    Institute of Pathology, Medical Faculty Mannheim of Heidelberg University, University Medical Center Mannheim, Mannheim, Germany.
  • Timo Gaiser
    Institute of Pathology, University Medical Center Mannheim, Mannheim, Germany.
  • Christof von Kalle
    National Center for Tumor Diseases, Department of Translational Oncology, German Cancer Research Center, Heidelberg, Germany.
  • Jochen S Utikal
    Department of Dermatology, Heidelberg University, Mannheim, Germany; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Stefan Fröhling
    National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
  • Maurice S Michel
    Department of Urology and Urological Surgery, Medical Faculty Mannheim of Heidelberg University, University Medical Center Mannheim, Mannheim, Germany.
  • Philipp Nuhn
    Department of Urology and Urological Surgery, Medical Faculty Mannheim of Heidelberg University, University Medical Center Mannheim, Mannheim, Germany.
  • Titus J Brinker
    National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.