Alteration of radiotherapy fractionation and concurrent chemotherapy: a new frontier in head and neck oncology?

Despite recent advances in multimodality management of patients with stage III-IV head and neck squamous cell carcinoma, the prognosis in these patients remains disappointing. In an attempt to improve treatment outcome, several teams recently investigated the role of altered fractionation radiotherapy in conjunction with systemic chemotherapy. The controlled trials that investigated this combined approach indicate that, although the magnitude of its effect was less marked for survival indices than for local-regional control, the addition of chemotherapy to altered fractionation regimens results in a clear improvement for these endpoints compared with hyperfractionated or accelerated regimens alone. The key challenge now is to optimize the synergism of these regimens in order to increase their therapeutic ratio in terms of both local-regional and systemic outcomes. This review is a critical appraisal of the real opportunities offered by the application of treatments aimed at increasing the dose intensity of radiotherapy delivered concurrently with cytotoxic drugs.