Sher David J, Schwartz David L, Nedzi Lucien, Khan Saad, Hughes Randall, Fidler Mary Jo, Koshy Matthew
Department of Radiation Oncology and Division of Outcomes and Health Services Research, UT Southwestern Medical Center, Dallas, TX, United States.
Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, United States.
Oral Oncol. 2016 Mar;54:58-67. doi: 10.1016/j.oraloncology.2015.12.008. Epub 2016 Jan 18.
Despite several randomized trials, the optimal chemotherapy paradigm for locally advanced oropharyngeal carcinoma (OPSCC) is controversial. This population-based analysis assessed the overall survival (OS) benefit of induction chemotherapy (IC) for patients with stage III-IVB OPSCC.
Patients in the National Cancer Database with stage III-IVA-B OPSCC treated with curative-dose radiotherapy and IC or concurrent chemotherapy (CRT) between 2003 and 2011 were eligible. The primary outcome was OS, and secondary endpoints included OS for high-risk (T4 and/or N3 disease) and human papillomavirus (HPV) subsets.
Of the 14,856 analyzed patients, 78% and 22% received CRT and IC, respectively. With a median follow-up for surviving patients of 44 months, the 5-year OS probability for the entire cohort was 66% (66% CRT vs. 64% IC, p=0.022). Multivariable survival analysis showed no significant difference between CRT and IC (hazard ratio, HR, 0.95 for IC, p=0.255), and sensitivity analyses to adjust for immortal time bias brought the HR to 1.0 (p=0.859). There was also no OS difference for high-risk patients. There was a trend in favor of CRT for HPV-positive OPSCC (HR 1.63 with IC, p=0.064), with a significant OS benefit for HPV-negative, high-risk OPSCC (HR 0.63, p=0.048).
For the vast majority of patients, including HPV-positive individuals, there was no difference in OS with IC, arguing for CRT to remain as the standard therapy. Subset analysis revealed a small cohort of aggressive cancer (T4/N3 HPV-negative) which may benefit from from IC, although selection bias could not be ruled out.
尽管进行了多项随机试验，但局部晚期口咽癌（OPSCC）的最佳化疗模式仍存在争议。这项基于人群的分析评估了诱导化疗（IC）对Ⅲ-ⅣB期OPSCC患者总生存期（OS）的益处。
2003年至2011年间，国家癌症数据库中接受根治性剂量放疗和IC或同步化疗（CRT）的Ⅲ-ⅣA-B期OPSCC患者符合条件。主要结局是OS，次要终点包括高危（T4和/或N3期疾病）和人乳头瘤病毒（HPV）亚组的OS。
在14856例分析患者中，分别有78%和22%接受了CRT和IC。存活患者的中位随访时间为44个月，整个队列的5年OS概率为66%（CRT为66%，IC为64%，p=0.022）。多变量生存分析显示CRT和IC之间无显著差异（风险比，HR，IC为0.95，p=0.255），针对不朽时间偏倚进行调整的敏感性分析使HR变为1.0（p=0.859）。高危患者的OS也无差异。HPV阳性OPSCC有倾向于CRT的趋势（IC的HR为1.63，p=0.064），HPV阴性高危OPSCC有显著的OS益处（HR为0.63，p=0.048）。
对于绝大多数患者，包括HPV阳性个体，IC的OS无差异，这表明CRT应继续作为标准治疗。亚组分析显示一小部分侵袭性癌症（T4/N3 HPV阴性）可能从IC中获益，尽管不能排除选择偏倚。
