• Anna Spreafico, Shao Hui Huang, Wei Xu, Roberta Granata, Chen-Shin Liu, John N Waldron, Eric Chen, Jolie Ringash, Andrew Bayley, Kelvin K W Chan, Andrew J Hope, John Cho, Albiruni A R Razak, Aaron Hansen, Raymond Jang, Bayardo Perez-Ordonez, Ilan Weinreb, Paolo Bossi, Ester Orlandi, Lisa F Licitra, Yuyao Song, Brian O'Sullivan, Lillian L Siu, and John Kim.
• Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
• Eur. J. Cancer. 2016 Nov 1; 67: 174-182.

AimThe aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV-) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT).Patients And MethodsA pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000-2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV-. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV- cohorts separately.ResultsA total of 404 HPV+ and 255 HPV- LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5-11.9) years. Three-year OS for cisplatin <200, =200, and >200 mg/m2 subgroups were 52%, 60%, and 72% (P = 0.001) for the HPV- and 91%, 90%, and 91% (P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m2 for the HPV- (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3-0.7, P < 0.001) but not for HPV+ (HR 0.6, 95% CI: 0.4-1.1, P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset (N = 107) with cisplatin >200 mg/m2 (HR 0.5, 95% CI: 0.2-1.1, P = 0.07).ConclusionsA survival benefit of cisplatin dose >200 mg/m2 is evident for HPV- LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose.Copyright © 2016 Elsevier Ltd. All rights reserved.

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