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dc.contributor.authorMehanna, H
dc.contributor.authorRapozo, D
dc.contributor.authorvon Zeidler, SV
dc.contributor.authorHarrington, KJ
dc.contributor.authorWinter, SC
dc.contributor.authorHartley, A
dc.contributor.authorNankivell, P
dc.contributor.authorSchache, AG
dc.contributor.authorSloan, P
dc.contributor.authorOdell, EW
dc.contributor.authorThavaraj, S
dc.contributor.authorHunter, KD
dc.contributor.authorShah, KA
dc.contributor.authorThomas, GJ
dc.contributor.authorLong, A
dc.contributor.authorAmel-Kashipaz, R
dc.contributor.authorBrown, RM
dc.contributor.authorConn, B
dc.contributor.authorHall, GL
dc.contributor.authorMatthews, P
dc.contributor.authorWeir, J
dc.contributor.authorYeo, Y
dc.contributor.authorPring, M
dc.contributor.authorWest, CML
dc.contributor.authorMcCaul, J
dc.contributor.authorGolusinski, P
dc.contributor.authorSitch, A
dc.contributor.authorSpruce, R
dc.contributor.authorBatis, N
dc.contributor.authorBryant, JL
dc.contributor.authorBrooks, JM
dc.contributor.authorJones, TM
dc.contributor.authorBuffa, F
dc.contributor.authorHaider, S
dc.contributor.authorRobinson, M
dc.coverage.spatialUnited States
dc.identifier.citationClinical Cancer Research, 2023, pp. OF1 - OF12
dc.description.abstractPURPOSE: 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 + adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR = 0.32; 95% confidence interval (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, 95% CI = 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.
dc.format.extentOF1 - OF12
dc.relation.ispartofClinical Cancer Research
dc.titleDeveloping and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma: The PREDICTR-OPC Study.
dc.typeJournal Article
rioxxterms.typeJournal Article/Review
pubs.organisational-groupICR/Primary Group
pubs.organisational-groupICR/Primary Group/ICR Divisions
pubs.organisational-groupICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-groupICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-groupICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-groupICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.publication-statusPublished online
icr.researchteamTargeted Therapy
dc.contributor.icrauthorHarrington, Kevin
icr.provenanceDeposited by Mr Arek Surman on 2024-01-17. Deposit type is initial. No. of files: 1. Files: 356.pdf

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