An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients with HPV-Associated Oropharyngeal Cancer.
2021
BACKGROUND HPV-associated oropharyngeal squamous cell carcinoma (OPCSCC) has excellent control rates compared to non-virally 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 HE 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 = 1.52-4.32, 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 = 1.32-3.94, 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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