期刊
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
卷 114, 期 4, 页码 609-617出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djab215
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资金
- National Cancer Institute of the National Institutes of Health [1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01CA216579-01A1, R01CA220581-01A1, 1U01 CA239055-01, R01CA249992-01A1, R01CA257612-01A1, 1U01CA239055-01, 1U01CA248226-01, 1U54CA254566-01]
- National Heart, Lung and Blood Institute [1R01HL15127701A1]
- National Institute for Biomedical Imaging and Bioengineering [1R43EB028736-01]
- National Center for Research Resources [1 C06 RR12463-01]
- United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service [IBX004121A]
- Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award [W81XWH19-1-0668]
- DOD Prostate Cancer Idea Development Award [W81XWH-15-1-0558]
- DOD Lung Cancer Investigator-Initiated Translational Research Award [W81XWH-18-1-0440]
- DOD Peer Reviewed Cancer Research Program [W81XWH-16-1-0329]
- Ohio Third Frontier Technology Validation Fund
- Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering
- Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University
- National Cancer Institute Cancer Center Support Grant [P30CA125123]
- United States Department of Veterans Affairs Clinical Sciences Research and Development Program [IK2 CX001953]
- Computational Genomic Epidemiology of Cancer Program at Case Comprehensive Cancer Center [T32CA094186]
This study investigates whether OP-TIL, a biomarker, can separate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials.
Background Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials. Methods Association between OP-TIL and patient outcome was explored on whole slide hematoxylin and eosin images from 439 stage I HPV-associated OPSCC patients across 6 institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence or death in the remaining 5 cohorts (n = 345). All statistical tests were 2-sided. Results OP-TIL separated stage I HPV-associated OPSCC patients with 30 or less pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS = 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52 to 4.32; P < .001), even after adjusting for age, smoking status, T and N classification, and treatment modality on multivariate analysis for DFS (hazard ratio = 2.27, 95% confidence interval = 1.32 to 3.94; P = .003). Conclusions OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation.
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