Altered fractionation and combined radio-chemotherapy approaches: pioneering new opportunities in head and neck oncology.

Squamous cell carcinoma of the head and neck (HNSCC) are increasingly treated by multimodality approaches combining surgery, radiotherapy and chemotherapy. Randomised controlled trials have demonstrated major improvements in loco-regional tumour control from altered fractionation radiotherapy, accelerated fractionation and hyperfractionation, as compared with conventional fractionation. This experience is summarised, and the limit as to how far these modifications can be taken is discussed. It is emphasised that radiation fractionation will need to be optimised separately in multimodality strategies. Combined chemotherapy and radiotherapy has also been shown in phase III trials to produce an improved survival and an improved disease control. Chemotherapy may be given as neoadjuvant, concurrent or adjuvant treatment and the biological rationales for each of these, and the data supporting them, are reviewed. Although, large meta-analyses have shown concurrent chemoradiation to be the most effective, there is still a strong rationale for trying to develop neoadjuvant and adjuvant schedules. New, more active drugs may be important in this context. As therapy is becoming more intense, a careful recording and reporting of treatment-related morbidity is a crucial element in estimating the therapeutic gain from competing therapeutic management strategies. Development of non-cytostatic drugs and individualization of therapy using molecular prognostic markers are exciting areas of research with a great potential for improving therapy in the next decade and these are briefly discussed. Finally, a number of avenues for further research are identified.