Journal article
An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer
JNCI : Journal of the National Cancer Institute, Vol.114(4), pp.609-617
04/11/2022
DOI: 10.1093/jnci/djab215
PMCID: PMC9002277
PMID: 34850048
Abstract
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.
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.
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).
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.
Details
- Title: Subtitle
- An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer
- Creators
- Germán Corredor - Case Western Reserve UniversityPaula Toro - Case Western Reserve UniversityCan Koyuncu - Case Western Reserve UniversityCheng Lu - Case Western Reserve UniversityChristina Buzzy - Case Western Reserve UniversityKaustav Bera - Case Western Reserve UniversityPingfu Fu - Case Western Reserve UniversityMitra Mehrad - Vanderbilt University Medical CenterKim A Ely - Vanderbilt University Medical CenterMojgan Mokhtari - Case Western Reserve UniversityKailin Yang - Cleveland ClinicDeborah Chute - Cleveland ClinicDavid J Adelstein - Case Western Reserve UniversityLester D R Thompson - Department of Pathology, Southern California Permanente Medical Group, Woodland Hills, CA, USAJustin A Bishop - The University of Texas Southwestern Medical CenterFarhoud Faraji - UC San Diego Health SystemWade Thorstad - Washington University in St. LouisPatricia Castro - Baylor College of MedicineVlad Sandulache - Baylor College of MedicineShlomo A Koyfman - Cleveland ClinicJames S Lewis - Vanderbilt University Medical CenterAnant Madabhushi - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- JNCI : Journal of the National Cancer Institute, Vol.114(4), pp.609-617
- DOI
- 10.1093/jnci/djab215
- PMID
- 34850048
- PMCID
- PMC9002277
- ISSN
- 0027-8874
- eISSN
- 1460-2105
- Grant note
- R43 EB028736 / NIBIB NIH HHS C06 RR012463 / NCRR NIH HHS P30 CA125123 / NCI NIH HHS T32 CA094186 / NCI NIH HHS U54 CA254566 / NCI NIH HHS I01 BX004121 / BLRD VA T32 DC000027 / NIDCD NIH HHS IK2 CX001953 / CSRD VA
- Language
- English
- Date published
- 04/11/2022
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696573602771
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