Deintensification Candidate Subgroups in Human Papillomavirus–Related Oropharyngeal Cancer According to Minimal Risk of Distant Metastasis

Author:

O'Sullivan Brian1,Huang Shao Hui1,Siu Lillian L.1,Waldron John1,Zhao Helen1,Perez-Ordonez Bayardo1,Weinreb Ilan1,Kim John1,Ringash Jolie1,Bayley Andrew1,Dawson Laura A.1,Hope Andrew1,Cho John1,Irish Jonathan1,Gilbert Ralph1,Gullane Patrick1,Hui Angela1,Liu Fei-Fei1,Chen Eric1,Xu Wei1

Affiliation:

1. Brian O'Sullivan, Shao Hui Huang, Lillian L. Siu, John Waldron, John Kim, Jolie Ringash, Andrew Bayley, Laura A. Dawson, Andrew Hope, John Cho, Fei-Fei Liu, and Eric Chen, Princess Margaret Hospital/University of Toronto; Helen Zhao, Jonathan Irish, Ralph Gilbert, Patrick Gullane, and Wei Xu, Princess Margaret Hospital; Bayardo Perez-Ordonez and Ilan Weinreb, University Health Network; Angela Hui and Fei-Fei Liu, Ontario Cancer Institute, Toronto, Ontario, Canada.

Abstract

Purpose To define human papillomavirus (HPV) –positive oropharyngeal cancers (OPC) suitable for treatment deintensification according to low risk of distant metastasis (DM). Patients and Methods OPC treated with radiotherapy (RT) or chemoradiotherapy (CRT) from 2001 to 2009 were included. Outcomes were compared for HPV-positive versus HPV-negative patients. Univariate and multivariate analyses identified outcome predictors. Recursive partitioning analysis (RPA) stratified the DM risk. Results HPV status was ascertained in 505 (56%) of 899 consecutive OPCs. Median follow-up was 3.9 years. HPV-positive patients (n = 382), compared with HPV-negative patients (n = 123), had higher local (94% v 80%, respectively, at 3 years; P < .01) and regional control (95% v 82%, respectively; P < .01) but similar distant control (DC; 90% v 86%, respectively; P = .53). Multivariate analysis identified that HPV negativity (hazard ratio [HR], 2.9; 95% CI, 2.0 to 5.0), N2b-N3 (HR, 2.9; 95% CI, 1.8 to 4.9), T4 (HR, 1.8; 95% CI, 1.2 to 2.9), and RT alone (HR, 1.8; 95% CI, 1.1 to 2.5) predicted a lower recurrence-free survival (RFS; all P < .01). Smoking pack-years > 10 reduced overall survival (HR, 1.72; 95% CI, 1.1 to 2.7; P = .03) but did not impact RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P = .65). RPA segregated HPV-positive patients into low (T1-3N0-2c; DC, 93%) and high DM risk (N3 or T4; DC, 76%) groups and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high DM risk (T3-4N3; DC, 72%) groups. The DC rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P = .02). Conclusion HPV-positive T1-3N0-2c patients have a low DM risk, but N2c patients from this group have a reduced DC when treated with RT alone and seem less suited for deintensification strategies that omit chemotherapy.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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