Claire Petit1, Benjamin Lacas2, Jean-Pierre Pignon2, Quynh Thu Le3, Vincent Grégoire4, Cai Grau5, Allan Hackshaw6, Björn Zackrisson7, Mahesh K B Parmar8, Ju-Whei Lee9, Maria Grazia Ghi10, Giuseppe Sanguineti11, Stéphane Temam12, Maurice Cheugoua-Zanetsie13, Brian O'Sullivan14, Marshall R Posner15, Everett E Vokes16, Juan J Cruz Hernandez17, Zbigniew Szutkowski18, Eric Lartigau19, Volker Budach20, Rafal Suwiński21, Michael Poulsen22, Shaleen Kumar23, Sarbani Ghosh Laskar24, Jean-Jacques Mazeron25, Branislav Jeremic26, John Simes27, Lai-Ping Zhong28, Jens Overgaard5, Catherine Fortpied29, Pedro Torres-Saavedra30, Jean Bourhis31, Anne Aupérin2, Pierre Blanchard32. 1. 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. 2. 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. 3. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. 4. Radiation Oncology Department, Centre Léon Bérard, Lyon, France. 5. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 6. Cancer Research UK and University College London Cancer Trials Centre, Cancer Institute, University College London Hospital, London, UK. 7. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. 8. Medical Research Council Clinical Trials Unit, University College London, London, UK. 9. ECOG-ACRIN Biostatistics Center, Dana Farber Cancer Institute, Boston, MA, USA. 10. Oncology Unit 2, Veneto Institute of Oncology-IRCCS, Padua, Italy. 11. Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy. 12. Service de Cancérologie Cervico-faciale, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France. 13. Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Oncostat U1018, Ligue Contre le Cancer, INSERM, Université Paris-Saclay, Villejuif, France. 14. Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 15. Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 16. Section of Hematology-Oncology, The University of Chicago Medical Center, Chicago, IL, USA. 17. Medical Oncology Department, University of Salamanca, Salamanca, Spain. 18. Department of Radiotherapy, Cancer Center, Marie Curie-Sklodowska Memorial Institute, Warsaw, Poland. 19. Department of Radiotherapy, Centre Oscar Lambret, Lille, France. 20. Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 21. Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland. 22. Radiation Oncology Services, Mater Centre, Brisbane, QLD, Australia. 23. Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. 24. Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India. 25. Département de Radiothérapie, Hôpital Pitié-Salpêtrière, Paris, France. 26. BioIRC Center for Biomedical Research, Kragujevac, Serbia. 27. NHMRC Clinical Trials Center, Camperdown, NSW, Australia. 28. Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 29. EORTC Headquarters, Brussels, Belgium. 30. NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA, USA. 31. Groupe d'Oncologie Radiothérapie Tête Et Cou, Tours, France; Department of Radiotherapy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 32. 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. Electronic address: pierreblanchard@gustaveroussy.fr.
Abstract
BACKGROUND: 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. METHODS: 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). FINDINGS: 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 (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%). INTERPRETATION: The 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. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.
BACKGROUND: 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. METHODS: 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). FINDINGS: 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 (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%). INTERPRETATION: The 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. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.
Authors: Ruta Zukauskaite; Christopher N Rumley; Christian R Hansen; Michael G Jameson; Yuvnik Trada; Jørgen Johansen; Niels Gyldenkerne; Jesper G Eriksen; Farhannah Aly; Rasmus L Christensen; Mark Lee; Carsten Brink; Lois Holloway Journal: Clin Transl Radiat Oncol Date: 2022-08-06
Authors: Philippe Gorphe; Pierre Blanchard; Gabriel C T E Garcia; Marion Classe; Caroline Even; Stéphane Temam; Ingrid Breuskin Journal: BMC Cancer Date: 2022-09-20 Impact factor: 4.638