Radiation-Induced Vascular Damage in Tumors: Implications of Vascular Damage in Ablative Hypofractionated Radiotherapy (SBRT and SRS)

Abstract

We have reviewed the studies on radiation-induced vascular changes in human and experimental tumors reported in the last several decades. Although the reported results are inconsistent, they can be generalized as follows. In the human tumors treated with conventional fractionated radiotherapy, the morphological and functional status of the vasculature is preserved, if not improved, during the early part of a treatment course and then decreases toward the end of treatment. Irradiation of human tumor xenografts or rodent tumors with 5-10 Gy in a single dose causes relatively mild vascular damages, but increasing the radiation dose to higher than 10 Gy/fraction induces severe vascular damage resulting in reduced blood perfusion. Little is known about the vascular changes in human tumors treated with high-dose hypofractionated radiation such as stereotactic body radiotherapy (SBRT) or stereotactic radiosurgery (SRS). However, the results for experimental tumors strongly indicate that SBRT or SRS of human tumors with doses higher than about 10 Gy/fraction is likely to induce considerable vascular damages and thereby damages the intratumor microenvironment, leading to indirect tumor cell death. Vascular damage may play an important role in the response of human tumors to high-dose hypofractionated SBRT or SRS.

Retrospective analysis of stereotactic ablative radiotherapy (SABR) for metastatic lung lesions (MLLs) in comparison with a contemporaneous cohort of primary lung lesions (PLLs)

“…Similar results were reported in another study on metastatic RCC (24), in which a univariate analysis revealed dose per fraction ≥9 Gy (HR =0.631; 95% CI, 0.429-0.931; P=0.021) to be predictive factor for (25). These data support the concept that a dose per fraction >10 Gy may independently of the histological type of the cancer induce severe vascular damage leading to indirect cell death (26).…”

3416 Outcomes and toxicity of radiotherapy for refractory bone and soft tissue sarcomas

“…As oxygen is an important factor in determining tumor response to RT, those data suggest that carbon-ion therapy may be superior to other forms of irradiation. Hypofractionated RT at higher doses per fraction may enhance radiation-induced tumor cell death by inducing endothelial apoptosis and subsequent microvascular damage (20,21). Alternatively, modern RT modalities, including CyberKnife, IMRT and stereotactic RT (SRT), deliver photons and provide larger irradiated doses with OAR sparing when compared with conventional techniques.…”

“…Doses >10 Gy likely produce secondary cell elimination due to enhanced vascular damage (20,21). Compared with conventional schedules, we used relatively large doses per fraction, which potentially caused differences in biological reactions following radiation exposure.…”

Stereotactic ablative radiotherapy and immunotherapy combinations: turning the future into systemic therapy?

“…In addition to inducing double-strand DNA breaks similar to conventionally fractionated treatment regimes, 21 RT delivered at higher doses per fraction (8-10 Gy) may induce more significant vascular, stromal and antitumour immune responses within the local tumour microenvironment, 22,23 leading to increased cell death and improved efficacy.…”