Song Chang W, Kim Mi-Sook, Cho L Chinsoo, Dusenbery Kathryn, Sperduto Paul W
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, K119 Diehl Hall, 424 Harvard Street S.E., MMC 494, Minneapolis, MN, 55455, USA,
Int J Clin Oncol. 2014 Aug;19(4):570-8. doi: 10.1007/s10147-014-0717-z. Epub 2014 Jul 5.
Stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) have been demonstrated to be highly effective for a variety of tumors. However, the radiobiological principles of SBRT and SRS have not yet been clearly defined. It is well known that newly formed tumor blood vessels are fragile and extremely sensitive to ionizing radiation. Various lines of evidence indicate that irradiation of tumors with high dose per fraction, i.e. >10 Gy per fraction, not only kills tumor cells but also causes significant damage in tumor vasculatures. Such vascular damage and ensuing deterioration of the intratumor environment then cause ischemic or indirect/secondary tumor cell death within a few days after radiation exposure, indicating that vascular damage plays an important role in the response of tumors to SBRT and SRS. Indications are that the extensive tumor cell death due to the direct effect of radiation on tumor cells and the secondary effect through vascular damage may lead to massive release of tumor-associated antigens and various pro-inflammatory cytokines, thereby triggering an anti-tumor immune response. However, the precise role of immune assault on tumor cells in SBRT and SRS has not yet been clearly defined. The "4 Rs" for conventional fractionated radiotherapy do not include indirect cell death and thus 4 Rs cannot account for the effective tumor control by SBRT and SRS. The linear-quadratic model is for cell death caused by DNA breaks and thus the usefulness of this model for ablative high-dose SBRT and SRS is limited.
立体定向体部放射治疗（SBRT）和立体定向放射外科治疗（SRS）已被证明对多种肿瘤具有高度有效性。然而，SBRT和SRS的放射生物学原理尚未明确界定。众所周知，新形成的肿瘤血管脆弱且对电离辐射极为敏感。各种证据表明，每次分割给予高剂量照射，即每次分割剂量>10 Gy，不仅会杀死肿瘤细胞，还会对肿瘤血管造成显著损伤。这种血管损伤以及随之而来的肿瘤内环境恶化会在辐射暴露后数天内导致缺血性或间接/继发性肿瘤细胞死亡，这表明血管损伤在肿瘤对SBRT和SRS的反应中起重要作用。有迹象表明，由于辐射对肿瘤细胞的直接作用以及通过血管损伤产生的间接作用导致的广泛肿瘤细胞死亡，可能会导致肿瘤相关抗原和各种促炎细胞因子大量释放，从而引发抗肿瘤免疫反应。然而，免疫攻击在SBRT和SRS中对肿瘤细胞的确切作用尚未明确界定。传统分割放疗的“4R”不包括间接细胞死亡，因此“4R”无法解释SBRT和SRS对肿瘤的有效控制。线性二次模型适用于由DNA断裂引起的细胞死亡，因此该模型在消融性高剂量SBRT和SRS中的实用性有限。
