Spreafico Anna, Huang Shao Hui, Xu Wei, Granata Roberta, Liu Chen-Shin, Waldron John N, Chen Eric, Ringash Jolie, Bayley Andrew, Chan Kelvin K W, Hope Andrew J, Cho John, Razak Albiruni A R, Hansen Aaron, Jang Raymond, Perez-Ordonez Bayardo, Weinreb Ilan, Bossi Paolo, Orlandi Ester, Licitra Lisa F, Song Yuyao, O'Sullivan Brian, Siu Lillian L, Kim John
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Eur J Cancer. 2016 Nov;67:174-182. doi: 10.1016/j.ejca.2016.08.013. Epub 2016 Sep 24.
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/m 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/m 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/m (HR 0.5, 95% CI: 0.2-1.1, P = 0.07).
A survival benefit of cisplatin dose >200 mg/m 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.
评估顺铂剂量调整对接受放化疗（CRT）的人乳头瘤病毒（HPV）相关（HPV+）和HPV非相关（HPV-）局部晚期头颈癌（LAHNC）患者预后的影响。
对2000年至2012年期间在两个三级学术癌症中心接受单药顺铂CRT治疗的III/IV期口咽癌（OPC）、原发灶不明癌（CUP）和喉下咽癌（LHC）患者进行汇总分析。通过p16染色和/或原位杂交确定HPV状态。假定LHC为HPV-。排除HPV状态不明的OPC/CUP患者。计算总生存期（OS）。多变量分析（MVA）分别评估顺铂剂量强度对HPV+和HPV-队列生存的影响。
共纳入404例HPV+和255例HPV-LAHNC（481例OPC、18例CUP、160例LHC）患者。中位随访时间为4.3（0.5-11.9）年。顺铂剂量<200、=200和>200mg/m亚组的HPV-患者3年总生存率分别为52%、60%和72%（P=0.001），HPV+患者分别为91%、90%和91%（P=0.30）。MVA证实，顺铂剂量>200mg/m对HPV-患者有生存获益（风险比[HR]0.5，95%置信区间[CI]：0.3-0.7，P<0.001），但对HPV+患者无生存获益（HR0.6，95%CI：0.4-1.1，P=0.104）。在HPV+ T4或N3高危亚组（N=107）中，顺铂剂量>200mg/m有更好的总生存趋势（HR0.5，95%CI：0.2-1.1，P=0.07）。
顺铂剂量>200mg/m对HPV-LAHNC患者有生存获益，但对HPV+队列总体无生存获益，尽管T4或N3亚组可能从更高累积顺铂剂量中获益。
