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Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19805 patients, on behalf of MACH-NC group

In Radiotherapy and oncology
By: Lacas B.
Contributor(s): Carmel A | Landais C | Wong SJ | Licitra L | Tobias JS | Burtness B | Grazia Ghi M | Cohen EEW | Grau C | Wolf G | Hitt R | Corvò R | Budach V | Kumar S | Ghosh Laskar S | Mazeron JJ | Zhong LP | Dobrowsky W | Ghadjar P | Fallai C | Zaktonik B | Sharma A | Bensadoun RJ | Grazia Ruo Redda M | Racadot S | Fountzilas G | Brizel D | Rovea P | Argiris A | Takácsi Nagy Z | Lee JW | Fortpied C | Harris J | Bourhis J | Aupérin A | Blanchard P | Pignon JP | MACH-NC Collaborative Group.
Material type: materialTypeLabelArticlePublisher: 2021Description: .Subject(s): Chemotherapy | Head and Neck Cancer | Individual Patient Data | Meta-analysis | Radiotherapy | Randomised Clinical Trials | Squamous Cell Carcinoma | Systematic Review In: Radiotherapy and oncologySummary: 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 Materials and methods: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT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.
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Articles Articles Tata Memorial Hospital
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Address for Corresponding Author: 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.

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