• Claire Petit, Benjamin Lacas, Jean-Pierre Pignon, Quynh Thu Le, Vincent Grégoire, Cai Grau, Allan Hackshaw, Björn Zackrisson, ParmarMahesh K BMKBMedical Research Council Clinical Trials Unit, University College London, London, UK., Ju-Whei Lee, Maria Grazia Ghi, Giuseppe Sanguineti, Stéphane Temam, Maurice Cheugoua-Zanetsie, Brian O'Sullivan, Marshall R Posner, Everett E Vokes, Juan J Cruz Hernandez, Zbigniew Szutkowski, Eric Lartigau, Volker Budach, Rafal Suwiński, Michael Poulsen, Shaleen Kumar, Ghosh LaskarSarbaniSDepartment of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India., Jean-Jacques Mazeron, Branislav Jeremic, John Simes, Lai-Ping Zhong, Jens Overgaard, Catherine Fortpied, Pedro Torres-Saavedra, Jean Bourhis, Anne Aupérin, Pierre Blanchard, and MACH-NC and MARCH Collaborative Groups.
• 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.
• Lancet Oncol. 2021 May 1; 22 (5): 727-736.

BackgroundRandomised, 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.MethodsWe 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).Findings115 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 (CLRTP) 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 CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%).InterpretationThe results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer.FundingsFrench Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.Copyright © 2021 Elsevier Ltd. All rights reserved.

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