Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery.

Conference Paper

PURPOSE: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). METHODS AND MATERIALS: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo--in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. RESULTS: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. CONCLUSIONS: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.

Full Text

Duke Authors

Cited Authors

  • Song, CW; Lee, Y-J; Griffin, RJ; Park, I; Koonce, NA; Hui, S; Kim, M-S; Dusenbery, KE; Sperduto, PW; Cho, LC

Published Date

  • September 1, 2015

Published In

Volume / Issue

  • 93 / 1

Start / End Page

  • 166 - 172

PubMed ID

  • 26279032

Pubmed Central ID

  • PMC4729457

Electronic International Standard Serial Number (EISSN)

  • 1879-355X

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2015.05.016

Conference Location

  • United States