The recently updated meta-analysis of chemotherapy in head and neck cancer (MACH-NC) demonstrated the benefit of the addition of chemotherapy in terms of overall survival in head and neck squamous cell carcinoma (HNSCC). The magnitude of the benefit according to tumour site is unknown as well as their potential interactions with patient or trial characteristics.

Eighty seven randomized trials performed between 1965 and 2000 were included in the present analysis. Patients were divided into four categories according to tumour location: oral cavity, oropharynx, hypopharynx and larynx. Patients with other tumour location were excluded (999, 5.7%). For each tumour location and chemotherapy timing, the logrank-test, stratified by trial, was used to compare treatments. The hazard ratios of death or relapse were calculated. Interactions between patient or trial characteristics and chemotherapy effect were studied.

Individual patient data of 16,192 patients were analysed, with a median follow-up of 5.6years. The benefit of the addition is consistent in all tumour locations, with hazard ratios between 0.87 and 0.88 (p-value of interaction=0.99). Chemotherapy benefit was higher for concomitant administration for all tumour locations, but the interaction test between chemotherapy timing and treatment effect was only significant for oropharyngeal (p<0.0001) and laryngeal tumours (p=0.05), and not for oral cavity (p=0.15) and hypopharyngeal tumours (p=0.30). The 5-year absolute benefits associated with the concomitant chemotherapy are 8.9%, 8.1%, 5.4% and 4% for oral cavity, oropharynx, larynx and hypopharynx tumours, respectively.

The benefit of the addition of chemotherapy to locoregional treatment is consistent in all tumour locations of HNSCC. The higher benefit of concomitant schedule was demonstrated only for oropharyngeal and laryngeal tumours but this may be only a consequence of a lack of power.