Impact of cisplatin dose intensity on human papillomavirus-related and -unrelated locally advanced head and neck squamous cell carcinoma.
The 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).



A 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.



A 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/m2subgroups 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/m2for 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).



A survival benefit of cisplatin dose >200 mg/m2is 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.
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Anna
A
Spreafico
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Shao Hui
SH
Huang
Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Canada.
Wei
W
Xu
Head and Neck Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, Italy.
Roberta
R
Granata
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Chen-Shin
CS
Liu
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
John N
JN
Waldron
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Eric
E
Chen
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Jolie
J
Ringash
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Andrew
A
Bayley
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Kelvin K W
KK
Chan
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Andrew J
AJ
Hope
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
John
J
Cho
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Albiruni A R
AA
Razak
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Aaron
A
Hansen
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Raymond
R
Jang
Laboratory Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Canada.
Bayardo
B
Perez-Ordonez
Laboratory Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Canada.
Ilan
I
Weinreb
Head and Neck Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, Italy.
Paolo
P
Bossi
Head and Neck Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, Italy.
Ester
E
Orlandi
Head and Neck Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, Italy.
Lisa F
LF
Licitra
Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Canada.
Yuyao
Y
Song
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Brian
B
O'Sullivan
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Lillian L
LL
Siu
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada. Electronic address: john.kim@rmp.uhn.on.ca.
John
J
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000473:pathology / Q000628:therapy* / Q000821:virology; D016022:Case-Control Studies; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy* / Q000821:virology; D007822:Laryngeal Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications*; D016016:Proportional Hazards Models; D020266:Radiotherapy, Conformal; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D002945:Cisplatin
Chemoradiotherapy; Cisplatin; Head and neck cancer; Human papillomavirus; Survival