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

高剂量低分割照射后的间接肿瘤细胞死亡:对立体定向放射治疗和立体定向放射手术的影响

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作者:Chang W Song, Yoon-Jin Lee, Robert J Griffin, Inhwan Park, Nathan A Koonce, Susanta Hui, Mi-Sook Kim, Kathryn E Dusenbery, Paul W Sperduto, L Chinsoo Cho

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.

Purpose

The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS).

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.

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