Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma.

Journal: The Journal of clinical investigation
PMID: 33651718

Abstract

BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.

Authors

  • Can F Koyuncu
    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
  • Cheng Lu
    Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China. lv_cheng0816@163.com.
  • Kaustav Bera
    Department of Biomedical Engineering, Case Western Reserve University School of Engineering, 2071 Martin Luther King Dr, Cleveland, OH 44106-7207 (M. Khorrami, K.B., A.M.); Departments of Internal Medicine (M. Khunger) and Solid Tumor Oncology (A.Z., P.P.), Cleveland Clinic, Cleveland, Ohio; Department of Internal Medicine, Maimonides Medical Center, Brooklyn, NY (R.T.); Department of Radiology, UT Southwestern Medical Center, Dallas, Tex (P.R.); Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio (P.F.); Department of Hematology and Oncology, New York University, New York, NY (V.V.); Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, Ohio (A.M.).
  • Zelin Zhang
    College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
  • Jun Xu
    Department of Nephrology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guizhou, China.
  • Paula Toro
    Department of Pathology, Universidad Nacional de Colombia, Bogotá, Colombia.
  • German Corredor
    Universidad Nacional de Colombia, Bogotá D.C, Colombia.
  • Deborah Chute
    Cleveland Clinic Foundation, Cleveland, Ohio, USA.
  • Pingfu Fu
    Department of Biomedical Engineering, Case Western Reserve University School of Engineering, 2071 Martin Luther King Dr, Cleveland, OH 44106-7207 (M. Khorrami, K.B., A.M.); Departments of Internal Medicine (M. Khunger) and Solid Tumor Oncology (A.Z., P.P.), Cleveland Clinic, Cleveland, Ohio; Department of Internal Medicine, Maimonides Medical Center, Brooklyn, NY (R.T.); Department of Radiology, UT Southwestern Medical Center, Dallas, Tex (P.R.); Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio (P.F.); Department of Hematology and Oncology, New York University, New York, NY (V.V.); Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, Ohio (A.M.).
  • Wade L Thorstad
    Washington University in St. Louis, St. Louis, Missouri, USA.
  • Farhoud Faraji
    UCSD, San Diego, California, USA.
  • Justin A Bishop
    University of Texas (UT) Southwestern Medical Center, Dallas, Texas, USA.
  • Mitra Mehrad
    Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Patricia D Castro
    Department of Otolaryngology, Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA.
  • Andrew G Sikora
    Department of Otolaryngology - Head and Neck Surgery, Head and Neck Cancer Translational Research Program, The Icahn School of Medicine at Mount Sinai, New York, New York.
  • Lester Dr Thompson
    Southern California Permanente Medical Group, Pasadena, California, USA.
  • R D Chernock
    Washington University in St. Louis, St. Louis, Missouri, USA.
  • Krystle A Lang Kuhs
    Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Jingqin Luo
    Department of Surgery, Washington University in St. Louis, St. Louis, MO, 63110, USA.
  • Vlad Sandulache
    Department of Otolaryngology, Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA.
  • David J Adelstein
    Cleveland Clinic Foundation, Cleveland, Ohio, USA.
  • Shlomo Koyfman
    Cleveland Clinic Foundation, Cleveland, Ohio, USA.
  • James S Lewis
    Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Anant Madabhushi
    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.

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