Benjamin Lacas1, Alexandra Carmel2, Cécile Landais2, Stuart J Wong3, Lisa Licitra4, Jeffrey S Tobias5, Barbara Burtness6, Maria Grazia Ghi7, Ezra E W Cohen8, Cai Grau9, Gregory Wolf10, Ricardo Hitt11, Renzo Corvò12, Volker Budach13, Shaleen Kumar14, Sarbani Ghosh Laskar15, Jean-Jacques Mazeron16, Lai-Ping Zhong17, Werner Dobrowsky18, Pirus Ghadjar19, Carlo Fallai7, Branko Zakotnik10, Atul Sharma20, René-Jean Bensadoun21, Maria Grazia Ruo Redda22, Séverine Racadot23, George Fountzilas24, David Brizel25, Paolo Rovea26, Athanassios Argiris27, Zoltán Takácsi Nagy28, Ju-Whei Lee29, Catherine Fortpied30, Jonathan Harris31, Jean Bourhis32, Anne Aupérin1, Pierre Blanchard33, Jean-Pierre Pignon1. 1. Cleveland Clinic Foundation, OH, USA; Institut Saint Catherine, France. 2. Cleveland Clinic Foundation, OH, USA. 3. CHU Henri Mondor, France. 4. Thomas Jefferson University Hospital, USA. 5. Genolier Swiss Oncology Network, Switzerland. 6. Oslo University Hospital, Norway. 7. Centre Hospitalier Universitaire de Tours, France. 8. Medical College of Wisconsin, USA. 9. H. Lee Moffitt Cancer Center & Research Institute, USA. 10. Centre Léon Bérard, France. 11. Centre Antoine Lacassagne, France. 12. Tata Memorial Centre Advanced Centre for Treatment, Research and Education in Cancer, India. 13. State University of New York Downstate Medical Center, USA. 14. Institut Curie, France. 15. EORTC Headquarters, Belgium. 16. Spanish Head and Neck Cancer Cooperative Group, Spain. 17. Ospedale Policlinico San Martino, Genoa, Italy. 18. Gustave Roussy, France. 19. Johns Hopkins Univ/Sidney Kimmel Cancer Center, MD, USA. 20. Cancer Research UK & UCL Cancer Trials Centre, UK. 21. Hôpital Henri Mondor, Créteil, France. 22. Rutgers Robert Wood Johnson and NJ Medical School, NJ, USA. 23. Princess Margaret Cancer Centre/University of Toronto, Ontario, Canada. 24. SAKK Coordinating Center, Switzerland. 25. Centre Georges François Leclerc, France. 26. Kragulevac University Hospital, Yugoslavia, Serbia. 27. University of Chicago, IL, USA. 28. University Medical Center Groningen, Netherlands. 29. Centre Jean Perrin, France. 30. Centre Oscar Lambret, France. 31. Rollins School of Public Health, Emory University, GA, USA. 32. Institut Saint Catherine, France; Stanford University School of Medicine, CA, USA. 33. Cleveland Clinic Foundation, OH, USA; Institut Saint Catherine, France; University of Texas-MD Anderson Cancer Center, USA. Electronic address: pierre.blanchard@gustavetoussy.fr.
Abstract
BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer.
BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer.
Authors: F Sanchíz; A Millá; J Torner; F Bonet; N Artola; L Carreño; L M Moya; D Riera; S Ripol; L Cirera Journal: Int J Radiat Oncol Biol Phys Date: 1990-12 Impact factor: 7.038
Authors: G E Laramore; C B Scott; M al-Sarraf; R E Haselow; T J Ervin; R Wheeler; J R Jacobs; D E Schuller; R A Gahbauer; J G Schwade Journal: Int J Radiat Oncol Biol Phys Date: 1992 Impact factor: 7.038
Authors: R J Toohill; J A Duncavage; T W Grossmam; T C Malin; R W Teplin; J F Wilson; R W Byhardt; J S Haas; J D Cox; T Anderson Journal: Laryngoscope Date: 1987-04 Impact factor: 3.325
Authors: A Paccagnella; M G Ghi; L Loreggian; A Buffoli; H Koussis; C A Mione; A Bonetti; F Campostrini; G Gardani; A Ardizzoia; D Dondi; M Guaraldi; R Cavallo; L Tomio; A Gava Journal: Ann Oncol Date: 2009-12-23 Impact factor: 32.976
Authors: Pierre Blanchard; Anne W M Lee; Alexandra Carmel; Ng Wai Tong; Jun Ma; Anthony T C Chan; Ruey Long Hong; Ming-Yuan Chen; Lei Chen; Wen-Fei Li; Pei-Yu Huang; Dora L W Kwong; Sharon S X Poh; Roger Ngan; Hai-Qiang Mai; Camille Ollivier; George Fountzilas; Li Zhang; Jean Bourhis; Anne Aupérin; Benjamin Lacas; Jean-Pierre Pignon Journal: Clin Transl Radiat Oncol Date: 2021-11-26
Authors: Jenny Bertholet; Paul-Henry Mackeprang; Silvan Mueller; Gian Guyer; Hannes A Loebner; Yanick Wyss; Daniel Frei; Werner Volken; Olgun Elicin; Daniel M Aebersold; Michael K Fix; Peter Manser Journal: Radiat Oncol Date: 2022-07-15 Impact factor: 4.309
Authors: Judith T Pruijssen; Ashwin Wenmakers; Roy P C Kessels; Vitoria Piai; Frederick J A Meijer; Sjoert A H Pegge; Jacqueline J Loonen; Anil M Tuladhar; Hendrik H G Hansen; Johannes H A M Kaanders; Joyce Wilbers Journal: BMC Cancer Date: 2022-03-05 Impact factor: 4.430