Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery

Abstract

Despite the increasing use of stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS) in recent years, the biological base of these high-dose hypo-fractionated radiotherapy modalities has been elusive. Given that most human tumors contain radioresistant hypoxic tumor cells, the radiobiological principles for the conventional multiple-fractionated radiotherapy cannot account for the high efficacy of SBRT and SRS. Recent emerging evidence strongly indicates that SBRT and SRS not only directly kill tumor cells, but also destroy the tumor vascular beds, thereby deteriorating intratumor microenvironment leading to indirect tumor cell death. Furthermore, indications are that the massive release of tumor antigens from the tumor cells directly and indirectly killed by SBRT and SRS stimulate anti-tumor immunity, thereby suppressing recurrence and metastatic tumor growth. The reoxygenation, repair, repopulation, and redistribution, which are important components in the response of tumors to conventional fractionated radiotherapy, play relatively little role in SBRT and SRS. The linear-quadratic model, which accounts for only direct cell death has been suggested to overestimate the cell death by high dose per fraction irradiation. However, the model may in some clinical cases incidentally do not overestimate total cell death because high-dose irradiation causes additional cell death through indirect mechanisms. For the improvement of the efficacy of SBRT and SRS, further investigation is warranted to gain detailed insights into the mechanisms underlying the SBRT and SRS.

The Reciprocity between Radiotherapy and Cancer Immunotherapy

“…of radiation may facilitate the maturation of antigen-presenting cells (61) and increase the infiltration of immune cells into the tumor (62). Low-dose radiation has been shown to normalize the tumor vasculature (39), but high-dose radiation could cause more vessel damage, thereby reducing blood flow and perfusion (63). Meanwhile, the lack of reoxygenation during the course of hypofractionated radiotherapy means that hypoxic tumors are more resistant to hypofractionated radiation (64).…”

Radiobiology of stereotactic body radiation therapy (SBRT)

“…3,8,13,14,[64][65][66] A recent paper, published by Kim reviews experimental data demonstrating the contribution of indirect cell death secondary to vascular damage to total tumor cell death. 67 On the contrary, Moding et al using dual recombinase technology, generated primary sarcomas in a genetically engineered mouse model with targeted genetic mutations specifically in tumor cells or endothelial cells and demonstrated that tumor cells, rather than endothelial cells, are critical targets that regulate sarcoma eradication by radiation therapy. 68 An additional hypothesis, linked to the previous theory, to explain the good clinical results of SBRT is the possibility that high doses of radiation can damage the perivascular niche where radioresistant stem cells are living.…”

Anatomic and functional imaging in the diagnosis of spine metastases and response assessment after spine radiosurgery

“…SSRS is thought, in part, to be effective due to ablation of tumor microvasculature. 20 Chu et al studied 19 lesions with DCE-MRI, with measurements including k trans , V p , area under the curve, and peak enhancement. Plasma volume was the strongest predictor of treatment response, with all treatment successes showing significant decrease in V p after RT.…”