TY - JOUR
T1 - Developing and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma
T2 - The PREDICTR-OPC Study
AU - Mehanna, Hisham
AU - Rapozo, Davy
AU - von Zeidler, Sandra V.
AU - Harrington, Kevin J.
AU - Winter, Stuart C.
AU - Hartley, Andrew
AU - Nankivell, Paul
AU - Schache, Andrew G.
AU - Sloan, Philip
AU - Odell, Edward W.
AU - Thavaraj, Selvam
AU - Hunter, Keith D.
AU - Shah, Ketan A.
AU - Thomas, Gareth J.
AU - Long, Anna
AU - Amel-Kashipaz, Rasoul
AU - Brown, Rachel M.
AU - Conn, Brendan
AU - Hall, Gillian L.
AU - Matthews, Paul
AU - Weir, Justin
AU - Yeo, Yen
AU - Pring, Miranda
AU - West, Catharine M.L.
AU - McCaul, James
AU - Golusinski, Pawel
AU - Sitch, Alice
AU - Spruce, Rachel
AU - Batis, Nikolaos
AU - Bryant, Jennifer L.
AU - Brooks, Jill M.
AU - Jones, Terence M.
AU - Buffa, Francesca
AU - Haider, Syed
AU - Robinson, Max
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research Inc.. All rights reserved.
PY - 2024/1/15
Y1 - 2024/1/15
N2 - Purpose: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC). Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC. Experimental Design: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012. We constructed tissue microarrays, which were stained and scored for 10 biomarkers. We then undertook multivariable regression of eight clinical parameters and 10 biomarkers on a development cohort of 600 patients. Models were validated on an independent, retrospectively collected, 385-patient cohort. Results: A total of 985 subjects (median follow-up 5.03 years, range: 4.73–5.21 years) were included. The final biomarker classifier, comprising p16 and survivin immunohistochemistry, high-risk human papillomavirus (HPV) DNA in situ hybridization, and tumor-infiltrating lymphocytes, predicted benefit from combined surgery þ adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR ¼ 0.32; 95% confidence interval (CI), 0.16–0.65; P ¼ 0.002], but not in the low-risk group (HR ¼ 0.4; 95% CI, 0.14–1.24; P ¼ 0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34, 95% CI ¼ 0.17–0.67, P ¼ 0.002, and in the low-risk group HR was 0.5, 95% CI ¼ 0.1–2.38, P ¼ 0.384. The concordance index was 0.73. Conclusions: We have developed a prognostic classifier, which also appears to demonstrate moderate predictive ability. External validation in a prospective setting is now underway to confirm this and prepare for clinical adoption.
AB - Purpose: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC). Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC. Experimental Design: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012. We constructed tissue microarrays, which were stained and scored for 10 biomarkers. We then undertook multivariable regression of eight clinical parameters and 10 biomarkers on a development cohort of 600 patients. Models were validated on an independent, retrospectively collected, 385-patient cohort. Results: A total of 985 subjects (median follow-up 5.03 years, range: 4.73–5.21 years) were included. The final biomarker classifier, comprising p16 and survivin immunohistochemistry, high-risk human papillomavirus (HPV) DNA in situ hybridization, and tumor-infiltrating lymphocytes, predicted benefit from combined surgery þ adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR ¼ 0.32; 95% confidence interval (CI), 0.16–0.65; P ¼ 0.002], but not in the low-risk group (HR ¼ 0.4; 95% CI, 0.14–1.24; P ¼ 0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34, 95% CI ¼ 0.17–0.67, P ¼ 0.002, and in the low-risk group HR was 0.5, 95% CI ¼ 0.1–2.38, P ¼ 0.384. The concordance index was 0.73. Conclusions: We have developed a prognostic classifier, which also appears to demonstrate moderate predictive ability. External validation in a prospective setting is now underway to confirm this and prepare for clinical adoption.
UR - http://www.scopus.com/inward/record.url?scp=85182732313&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-1013
DO - 10.1158/1078-0432.CCR-23-1013
M3 - Article (Academic Journal)
C2 - 37870417
SN - 1078-0432
VL - 30
SP - 356
EP - 367
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -