[Do dose constraints to organs at risk need to be adapted when irradiation is combined with drug therapy?]

Therapeutic strategies combining irradiation and drugs including chemotherapy, hormonotherapy, but also more recently targeted therapy and immunotherapy are routinely used for cancer treatment. Nevertheless, combined treatments usually lead to a rise in toxicity. In order to increase the therapeutic ratio in favour of a multimodality treatment, adapting dose constraints to organs at risk may be the key to lower the risk of toxicity. A review of the literature was conducted, focusing on the toxicity in dose-limiting organs at risk when radiation therapy is associated with drugs. Four situations were differentiated, including : 1) some contraindicated combinations due to an inacceptable increased of toxicity, or recommendations of careful use with restricted indications, reduction in prescribed dose, or severe dose constraints to organs at risk, 2) combined treatments without increased toxicity with no arguments for adjusted dose constraints, 3) associations with higher risk of toxicity, for which dose constraints could be adapted, 4) combined therapies with limited tolerance data, prohibiting their use out of clinical trials.