《柳叶刀肿瘤分册》2007年7月27日在线先发
http://thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30458-8/fulltext
头颈部肿瘤分割放疗的作用（MARCH）：最新的一项荟萃分析
背景
“头颈部鳞癌放疗的荟萃分析（MARCH）”表明，与常规放疗相比，改变放疗分割与总生存率、无进展生存率提高相关，且超分割放疗获益最大。这项更新分析旨在确认和解释超分割放疗优于其他改变分割放疗方案，并在纳入新的临床试验、同步化疗的背景下，评估改变放疗分割的获益情况。
方法
对于这项更新的荟萃分析，我们检索了书目数据库、临床试验注册，还检索了2009年1月1日至2015年7月15日期间完成的、不论发表与否的随机化临床试验的会议汇编，对初始或术后常规分割放疗对比改变分割放疗（比较1）、或常规分割放疗联合同步化疗对比单纯改变分割放疗（比较2）进行了比较。符合分析条件的临床试验必须是在1970年1月1日或之后开始随机化分组，并于2010年12月31日前有获益；必须在对治疗分组知情的情况下进行随机化分组；必须包含正在进行一线根治治疗的口腔、口咽、喉咽、喉非转移性鳞癌患者。包含非常规放疗对照组的临床试验、研究超分割放疗的临床试验、或者纳入试验者大部分为鼻咽癌的临床试验予以剔除。在改变分割的三种类型中对临床试验进行分组：超分割、中速分割和加速分割。收集每名患者数据，并在意向性治疗原则的基础上，用固定效应模型将每名患者的数据进行结合。主要终点为总生存率。
结果
比较1（常规分割放疗对比改变分割放疗）纳入了33个临床试验、11423名患者，改变分割放疗与总生存率明显获益相关（风险比[HR]，0.94，95%CI，0.90-0.98；p=0.0033），5年绝对相差3.1%（95%CI，1.3-4.9）、10年绝对相差1.2%（−0.8-3.2），我们发现分割类型和治疗效应间交互作用明显（p=0.051），总生存获益仅限于超分割组（HR，0.83，0.74-0.92），5年绝对相差8.1%（3.4-12.8）、10年绝对相差3.9%（−0.6-8.4）。比较2（常规分割放疗联合同步化疗对比单纯改变分割放疗）纳入了5个临床试验、986名患者，改变分割放疗与同步放化疗相比，总生存率明显差（HR，1.22，1.05-1.42；p=0.0098），5年绝对相差−5.8%（−11.9至0.3）、10年绝对相差−5.1%（−13.0至2.8）。
解释
这项更新比MARCH第一版有更多的患者和更长的随访期，证实超分割放疗连同同步化疗是局部晚期头颈鳞癌的标准治疗，但（单纯）超分割放疗与同步放化疗之间的比较仍有待专门验证。
Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis
Background
The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.
Methods
For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival.
Findings
Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8).
Interpretation
This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested.
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