Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Oncostat U1018, Ligue Contre le Cancer, INSERM, Université Paris-Saclay, Villejuif, France; Department of Radiation Oncology, Gustave Roussy Cancer Campus, Université Paris-Sud, Université Paris-Saclay, F-94805 Villejuif, France; Groupe d'Oncologie Radiothérapie Tête Et Cou, Tours, France.
Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Oncostat U1018, Ligue Contre le Cancer, INSERM, Université Paris-Saclay, Villejuif, France; Groupe d'Oncologie Radiothérapie Tête Et Cou, Tours, France.
Lancet Oncol. 2021 May;22(5):727-736. doi: 10.1016/S1470-2045(21)00076-0. Epub 2021 Apr 13.
Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other.
We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies).
115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRT) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRT (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (IC-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and IC followed by CLRT (80%).
The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or IC-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer.
French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.
随机对照试验和荟萃分析表明，同期放化疗或超分割放疗在治疗局部晚期头颈部癌症方面具有生存获益。然而，这些治疗方法的相对疗效尚不清楚。我们旨在确定一种治疗方法是否优于另一种。
我们基于 Meta-Analysis of Chemotherapy in Head and Neck Cancer（MACH-NC）和 Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck（MARCH）荟萃分析中个体患者数据进行了频率论网络荟萃分析。纳入了 1980 年 1 月 1 日至 2016 年 12 月 31 日期间入组非转移性头颈部鳞状细胞癌患者的随机对照试验。我们使用两步随机效应方法和分层试验的对数秩检验来比较治疗方法，以局部区域治疗作为参考。总生存期是主要终点。全球 Cochran Q 统计量用于评估同质性和一致性，P 评分用于对治疗方法进行排序（得分越高表示治疗效果越好）。
115 项随机对照试验，共纳入了 1980 年 1 月 1 日至 2012 年 4 月 30 日期间的患者，共产生了 154 项比较（28978 例患者，19253 例死亡和 20579 例进展事件）。治疗方法分为 16 种模式，其中有 35 种直接比较类型。基于所有试验的中位随访时间为 6.6 年（IQR 5.0-9.4）。同期放化疗联合超分割放疗（HFCRT）被评为总生存期最佳治疗方法（P 评分 97%；与局部区域治疗相比，风险比为 0.63[95%CI 0.51-0.77]）。与局部区域治疗加顺铂为基础的同期放化疗联合化疗（CLRT）相比，HFCRT 的风险比为 0.82（95%CI 0.66-1.01）。HFCRT 的优势在敏感性分析中仍然稳健。其他三种治疗方法的 P 评分更高，但与 CLRT 相比，总生存期的 HR 没有显著改善（P 评分 78%）：紫杉醇、顺铂和氟尿嘧啶诱导化疗后局部区域治疗（IC-LRT；89%）、同期放化疗加速放疗（82%）和 IC 后加 CLRT（80%）。
这项网络荟萃分析的结果表明，进一步强化同期放化疗，使用 HFCRT 或 IC-CLRT，可能会改善局部晚期头颈部癌症的治疗效果。
法国国家癌症研究所、法国抗癌联盟和 ARC 基金会。
