Prediction of immunochemotherapy response for diffuse large B-cell lymphoma using artificial intelligence digital pathology.

Journal: The journal of pathology. Clinical research
PMID:

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and prevalent subtype of aggressive non-Hodgkin lymphoma that poses diagnostic and prognostic challenges, particularly in predicting drug responsiveness. In this study, we used digital pathology and deep learning to predict responses to immunochemotherapy in patients with DLBCL. We retrospectively collected 251 slide images from 216 DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with their immunochemotherapy response labels. The digital pathology images were processed using contrastive learning for feature extraction. A multi-modal prediction model was developed by integrating clinical data and pathology image features. Knowledge distillation was employed to mitigate overfitting on gigapixel histopathology images to create a model that predicts responses based solely on pathology images. Based on the importance derived from the attention mechanism of the model, we extracted histological features that were considered key textures associated with drug responsiveness. The multi-modal prediction model achieved an impressive area under the ROC curve of 0.856, demonstrating significant associations with clinical variables such as Ann Arbor stage, International Prognostic Index, and bulky disease. Survival analyses indicated their effectiveness in predicting relapse-free survival. External validation using TCGA datasets supported the model's ability to predict survival differences. Additionally, pathology-based predictions show promise as independent prognostic indicators. Histopathological analysis identified centroblastic and immunoblastic features to be associated with treatment response, aligning with previous morphological classifications and highlighting the objectivity and reproducibility of artificial intelligence-based diagnosis. This study introduces a novel approach that combines digital pathology and clinical data to predict the response to immunochemotherapy in patients with DLBCL. This model shows great promise as a diagnostic and prognostic tool for clinical management of DLBCL. Further research and genomic data integration hold the potential to enhance its impact on clinical practice, ultimately improving patient outcomes.

Authors

  • Jeong Hoon Lee
    1 Division of Biomedical Informatics, Seoul National University Biomedical Informatics, Seoul National University College of Medicine , Seoul, Korea.
  • Ga-Young Song
    Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
  • Jonghyun Lee
    Civil and Environmental Engineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA; Water Resources Research Center, University of Hawaii at Manoa, Hawaii, HI 96822, USA. Electronic address: jonghyun.harry.lee@hawaii.edu.
  • Sae-Ryung Kang
    Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun 58128, Korea.
  • Kyoung Min Moon
    Department of Pulmonary, Allergy, and Critical Care Medicine, Gangneung Asan Hospital, College of Medicine, University of Ulsan, 38, Bangdong-gil, Sacheon-myeon, Gangneung-si, 25440, Gangwon-do, Republic of Korea. pulmogicu@ulsan.ac.kr.
  • Yoo-Duk Choi
    Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea.
  • Jeanne Shen
    Center for Artificial Intelligence in Medicine and Imaging, Stanford University, 1701 Page Mill Road, Palo Alto, CA, 94304, USA. jeannes@stanford.edu.
  • Myung-Giun Noh
    Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea.
  • Deok-Hwan Yang
    Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.