Biological Principles of Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiation Surgery (SRS): Indirect Cell Death

Int J Radiat Oncol Biol Phys. 2021 May 1;110(1):21-34. doi: 10.1016/j.ijrobp.2019.02.047. Epub 2019 Mar 2.

Abstract

Purpose: To review the radiobiological mechanisms of stereotactic body radiation therapy stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS).

Methods and materials: We reviewed previous reports and recent observations on the effects of high-dose irradiation on tumor cell survival, tumor vasculature, and antitumor immunity. We then assessed the potential implications of these biological changes associated with SBRT and SRS.

Results: Irradiation with doses higher than approximately 10 Gy/fraction causes significant vascular injury in tumors, leading to secondary tumor cell death. Irradiation of tumors with high doses has also been reported to increase the antitumor immunity, and various approaches are being investigated to further elevate antitumor immunity. The mechanism of normal tissue damage by high-dose irradiation needs to be further investigated.

Conclusions: In addition to directly killing tumor cells, high-dose irradiation used in SBRT and SRS induces indirect tumor cell death via vascular damage and antitumor immunity. Further studies are warranted to better understand the biological mechanisms underlying the high efficacy of clinical SBRT and SRS and to further improve the efficacy of SBRT and SRS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Vessels / pathology
  • Blood Vessels / radiation effects
  • Carcinoma 256, Walker / blood supply
  • Carcinoma 256, Walker / pathology
  • Carcinoma 256, Walker / radiotherapy
  • Cell Death* / genetics
  • Cell Survival / radiation effects
  • DNA Damage
  • Dose Fractionation, Radiation
  • Endothelium, Vascular / cytology
  • Humans
  • Immunogenic Cell Death
  • Mice
  • Mice, Nude
  • Neoplasms / blood supply
  • Neoplasms / immunology
  • Neoplasms / radiotherapy*
  • Organs at Risk / blood supply
  • Organs at Risk / radiation effects
  • Radiobiology
  • Radiosurgery / methods*
  • Rats
  • Tumor Hypoxia / radiation effects
  • Xenograft Model Antitumor Assays