Association d’une chimiothérapie ou d’un traitement ciblé à une irradiation stéréotaxique : état des lieux et recommandations préliminaires

Abstract

The clinical management of systemic treatments and irradiation has long been studied for conventional irradiation. Yet, many associations are of difficult management and some drugs are contra-indicated in the concomitant setting owing to excessive toxicities. Sequential regimens using a therapeutic window of variable duration (based on drug half-life and tissue wash out) between each modality may be preferred for easier logistics and to avoid toxicities. The use of intra- and extracranial stereotactic ablative radiation therapy (hypofractionated) is expanding rapidly. Yet, little is known regarding associations between stereotactic ablative radiation therapy and systemic treatments. The short stereotactic ablative radiation therapy course in one day to two weeks offers a theoretical advantage compared to longer conventional irradiation with respect to shorter discontinuation of therapy. This may be of particular interest in situations where cancer is addicted to systemic treatment. While it is believed that stereotactic ablative radiation therapy might be safer because of limited irradiation volumes and steep gradients sparing most organs at risk, it should be noted that irradiation of normal tissues cannot be considered null; that stereotactic ablative radiation therapy has vascular effects in addition to other cell death radiation-induced mechanisms and cancer progression with discontinuation of systemic treatment is often reversible. To date, based on several phase II studies, combined stereotactic ablative radiation therapy and cetuximab can be recommended in head and neck tumours. Other stereotactic ablative radiation therapy-based combinations require prospective phase I–II studies and sufficient therapeutic window (in the order of at least 5 half-lives) between the systemic and local modalities must be left in routine practice.