Developing and validating a multivariable prognostic-predictive classifier for treatment escalation of oropharyngeal squamous cell carcinoma: the PREDICTR-OPC study
Author
Mehanna, HishamRapozo, Davy
von Zeidler, Sandra V
Harrington, Kevin J
Winter, Stuart C
Hartley, Andrew
Nankivell, Paul
Schache, Andrew G
Sloan, Philip
Odell, Edward W
Thavaraj, Selvam
Hunter, Keith D
Shah, Ketan A
Thomas, Gareth J
Long, Anna
Amel-Kashipaz, Rasoul
Brown, Rachel M
Conn, Brendan
Hall, Gillian L
Matthews, Paul
Weir, Justin
Yeo, Yen
Pring, Miranda
West, Catharine M L
McCaul, James
Golusinski, Pawel
Sitch, Alice
Spruce, Rachel
Batis, Nikolaos
Bryant, Jennifer L
Brooks, Jill M
Jones, Terence M
Buffa, Francesca
Haider, Syed
Robinson, Max
Publication date
2023-10-23
Metadata
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Purpose: Whilst 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 centres in UK and Poland between 1999-2012. 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: 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 HPV DNA in-situ hybridisation, and tumour-infiltrating lymphocytes predicted benefit from combined surgery+adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group (3yr OS 63.1% versus 41.1%, respectively, HR=0.32, 95% CI 0.16 -0.65, p=0.002), but not in the low-risk group HR=0.4, 95%CI 0.14-1.24, p=0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34,95% CI = 0.17-0.67, p=0.002, and in the low-risk group HR was 0.5, CI 95% = 0.1-2.38, p=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.Citation
Mehanna H, Rapozo D, von Zeidler SV, Harrington KJ, Winter SC, Hartley A, Nankivell P, Schache AG, Sloan P, Odell EW, Thavaraj S, Hunter KD, Shah KA, Thomas GJ, Long A, Amel-Kashipaz R, Brown RM, Conn B, Hall GL, Matthews P, Weir J, Yeo Y, Pring M, West CML, McCaul J, Golusinski P, Sitch A, Spruce R, Batis N, Bryant JL, Brooks JM, Jones TM, Buffa F, Haider S, Robinson M. Developing and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma: The PREDICTR-OPC Study. Clin Cancer Res. 2024 Jan 17;30(2):356-367. doi: 10.1158/1078-0432.CCR-23-1013.Type
ArticleAdditional Links
https://aacrjournals.org/clincancerresPMID
37870417Journal
Clinical Cancer ResearchPublisher
American Association for Cancer Researchae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-23-1013