Effects of high-dose irradiation on vascularization: Physiopathology and clinical consequences

A review of the literature has been conducted to better understand the effect of stereotactic radiotherapy on tumour vascularization and their consequences. High irradiation doses cause the death of endothelial cells by apoptosis through the ceramide pathway. Vascular consequences are multiple: increased permeability, decreased blood flow, increased hypoxia and tumoral necrosis. This necrosis causes an indirect death of the cancer cells in the days following the irradiation. The importance of indirect cell death in tumour control remains controversial, but it can explain the good clinical results of stereotactic radiotherapy. Stereotactic radiotherapy is a treatment of the tumour microenvironment. Tumour recurrence in this hypoxic environment is slower through disturbance of revascularization mechanisms but also more aggressive, with increased resistance to treatment and a higher risk of metastasis. In a longer time, vascular damage leads to chronic inflammation and a dysfunctional healing process resulting in vascular occlusion. This phenomenon is used in the treatment of arteriovenous malformations but is also responsible for damage to healthy tissues responsible for chronic complications. This is why high-dose irradiation can only be delivered using stereotactic radiotherapy, which reduces the irradiated volume. (C) 2019 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.