Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma.
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 t...
| Published in: | Journal of Clinical Investigation Vol. 131; no. 8; pp. 1 - 12 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
American Society for Clinical Investigation
4/15/2021
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=149862401&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149862401 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00219738 0YX jtl: Journal of Clinical Investigation issn: 00219738 maglogo: N pubinfo: dt: 4/15/2021 vid: 131 iid: 8 pid: 11983 pub: American Society for Clinical Investigation place: Ann Arbor, Michigan artinfo: ui: 149862401 149862401 NLM33651718 149862401 10.1172/JCI145488 NLM33651718 149862401 ppf: 1 ppct: 11 formats: tig: atl: Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma. aug: au: Koyuncu, Can F. Cheng Lu Bera, Kaustav Zelin Zhang Jun Xu Toro, Paula Corredor, German Chute, Deborah Pingfu Fu Thorstad, Wade L. Faraji, F. Bishop, Justin A. Mehrad, Mitra Castro, Patricia D. Sikora, Andrew G. Thompson, Lester D. R. Chernock, R. D. Lang Kuhs, Krystle A. Jingqin Luo Sandulache, Vlad affil: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA sug: subj: Proteins Metabolism Head and Neck Neoplasms Mortality Head and Neck Neoplasms Metabolism Image Processing, Computer Assisted Head and Neck Neoplasms Pathology Female Middle Age Survival Human Prognosis Male Aged Prospective Studies Comparative Studies Multicenter Studies Evaluation Research Validation Studies Funding Source Middle Aged: 45-64 years Aged: 65+ years Female Male ab: 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. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|