Biological Effects of Advanced Radiotherapy Techniques Beyond the Irradiated Target Volume

Abstract

Radiotherapy is used in the treatment of approximately half of all patients with cancer, and technological advances over the past decades have progressively improved the precision with which the radiation dose can be matched to the target volume. Techniques such as three-dimensional conformal radiotherapy, intensity-modulated radiation therapy, and volumetric modulated arc therapy (VMAT) allow better sparing of healthy tissue and have enabled the introduction of schedules implementing higher radiation doses, including hypofractionated stereotactic body radiotherapy (SBRT), and boost techniques including intraoperative radiotherapy (IORT). However, delivering higher radiation doses with modern techniques such as VMAT expose tissues distant from the target volume to low, out-of-field doses of radiation of varying energy, and the biological consequences of this exposure have not been fully characterized. Similarly, although IORT reduces the dose delivered to healthy tissue while irradiating the tumour bed directly during surgery, its influence on the postoperative wound microenvironment and on the behaviour of residual tumour cells is incompletely understood. This review summarizes in vitro evidence addressing these two questions.