Outcome-Supervised Deep Learning on Pathologic Whole Slide Images for Survival Prediction of Immunotherapy in Patients with Non-Small Cell Lung Cancer.

Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Published Date:

Abstract

Although programmed death-(ligand) 1 (PD-(L)1) inhibitors are marked by durable efficacy in patients with non-small cell lung cancer (NSCLC), approximately 60% of the patients still suffer from recurrence and metastasis after PD-(L)1 inhibitor treatment. To accurately predict the response to PD-(L)1 inhibitors, we presented a deep learning model using a Vision Transformer (ViT) network based on hematoxylin and eosin (H&E)-stained specimens of patients with NSCLC. Two independent cohorts of patients with NSCLC receiving PD-(L)1 inhibitors from Shandong Cancer Hospital and Institute and Shandong Provincial Hospital were enrolled for model training and external validation, respectively. Whole slide images (WSIs) of H&E-stained histologic specimens were obtained from these patients and patched into 1024 × 1024 pixels. The patch-level model was trained based on ViT to identify the predictive patches, and patch-level probability distribution was performed. Then, we trained a patient-level survival model based on the ViT-Recursive Neural Network framework and externally validated it in the Shandong Provincial Hospital cohort. A total of 291 WSIs of H&E-stained histologic specimens from 198 patients with NSCLC in Shandong Cancer Hospital and 62 WSIs from 30 patients with NSCLC in Shandong Provincial Hospital were included in the model training and validation. The model achieved an accuracy of 88.6% in the internal validation cohort and 81% in the external validation cohort. The survival model also remained a statistically independent predictor of survival from PD-(L)1 inhibitors. In conclusion, the outcome-supervised ViT-Recursive Neural Network survival model based on pathologic WSIs could be used to predict immunotherapy efficacy in patients with NSCLC.

Authors

  • Butuo Li
    Department of Radiation Oncology, Shandong Cancer Hospital & Institute, Jinan, China.
  • Linlin Yang
    Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Huan Zhang
    Department of Plant Protection, Zhejiang University, 866 Yuhangtang Road, 5 Hangzhou 310058, China.
  • Haoqian Li
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • Chao Jiang
    Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
  • Yueyuan Yao
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • Shuping Cheng
    College of Life Science and Bioengineering, Beijing University of Technology, Intelligent Physiological Measurement and Clinical Translation, Beijing International Base for Scientific and Technological Cooperation, Beijing, 100124, China.
  • Bing Zou
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China.
  • Bingjie Fan
    Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China.
  • Taotao Dong
    Department of Obstetrics and Gynecology Qilu Hospital Cheeloo College of Medicine Shandong University Jinan Shandong China.
  • Linlin Wang
    Guangdong-Hong Kong-Macao Greater Bay Area Artificial Intelligence Application Technology Research Institute, Shenzhen Polytechnic University, Shenzhen, China.