Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.
Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.
复制标题
DOI：
10.1016/s1470-2045(17)30458-8
复制
发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
MARCH Collaborative Group
中科院分区：
文献类型：
--
作者：
Lacas B;Bourhis J;Overgaard J;Zhang Q;Grégoire V;Nankivell M;Zackrisson B;Szutkowski Z;Suwiński R;Poulsen M;O'Sullivan B;Corvò R;Laskar SG;Fallai C;Yamazaki H;Dobrowsky W;Cho KH;Beadle B;Langendijk JA;Viegas CMP;Hay J;Lotayef M;Parmar MKB;Aupérin A;van Herpen C;Maingon P;Trotti AM;Grau C;Pignon JP;Blanchard P;MARCH Collaborative Group
《头颈部鳞状细胞癌放射治疗的荟萃分析》(3月份)显示，与传统放射治疗相比，改变分割放射治疗可改善总体和无进展生存率，其中超分割放射治疗的益处最大。这一更新旨在证实和解释超分割放射治疗相对于其他改变的分割放射治疗方案的优越性，并在同时进行化疗和纳入新的试验的情况下评估改变分割放射治疗的益处。在这项更新的荟萃分析中，我们搜索了在2009年1月1日至2015年7月15日期间进行的已发表或未发表的随机试验的文献数据库、试验登记和会议记录，比较了初次或术后常规分割放射治疗与改良分割放射治疗(比较1)或常规分割放射治疗加化疗与单纯改变分割放射治疗(比较2)。符合条件的试验必须在1970年1月1日或之后开始随机分组，并在2010年12月31日之前完成应计；必须以事先不知道治疗分配的方式进行随机分组；必须包括正在接受一线治疗的口腔、口咽、下咽或喉部非转移性鳞状细胞癌患者。包括非常规放射治疗对照组、研究低分割放射治疗或主要包括鼻咽癌在内的试验被排除在外。试验被分成三种类型的改变分级：超分割、中等加速和非常加速。收集患者个体数据，并与基于意向治疗原则的固定效应模型相结合。主要终点是总体存活率。比较1(常规分割放射治疗与改良分割放射治疗)包括33个试验和11423例患者。改变分割放射治疗可显著提高总生存率(危险比[HR]0·94，95%可信区间0·90~0·98；p=0·0033)，5年的绝对差值为3·1%(95%可信区间1·3~4·9)，10年的绝对差值为1·2%(−0·8~3·2)。我们发现分割类型与治疗效果之间存在显著的交互作用(p=0.051)，总体生存益处仅限于超分割组(HR 0.83，0.74~0.92)，5年的绝对差值为8.1%(3.4~12.8)，10年的绝对差值为3.9%(−0.6~8.4)。比较2(常规分割放射治疗加同期化疗与单纯改变分割放射治疗)包括5个试验和986名患者。放疗后总生存率明显低于同期放化疗(HR1·22，1·05~1·42；p=0.0098)，5年−为5.8%(−11.9~0.3)，10年−为5.1%(−13.0~2.8)。这一更新证实，与3月份的第一个版本相比，超分割放射治疗与同期的放化疗一起，是治疗局部晚期头颈部鳞状细胞癌的标准治疗方案，患者数量更多，随访时间也更长。超分割放射治疗和同期放化疗之间的比较仍有待具体测试。
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. 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updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered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. 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). 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.