Controversies and challenges regarding the impact of radiation therapy on survival.

Novel irradiation techniques and radiosensitizing strategies revealed their interest for improving the antitumor efficacy of radiation therapy (RT) and thus for reducing locoregional failures. We analyzed the relevance of these strategies with regard to their impact on survival. The examples of the targeted molecular agent cetuximab and dose intensification in head and neck and lung cancer show that this benefit in local control is associated with a survival benefit. Large meta-analyses comparing sequential versus concurrent chemoradiation have also highlighted that improvement in local control is a major contributor to the survival benefit observed in chemoradiation trials. This close link between local control and survival encourages us to pursue our efforts to further improve the efficacy of RT. In some cases, the survival benefit afforded by radiotherapy is however marginal. The better understanding of the impact of local control on overall survival might allow optimization of clinical trials designs.