Stereotactic body radiation therapy (SBRT) has made the hypofractionation of high doses delivered in a few sessions more acceptable. While the benefits of hypofractionated SBRT have been attributed to additional vascular, immune effects, or specific cell deaths, a radiobiological and mechanistic model is still needed. By considering each session of SBRT, the dose is divided into hundreds of minibeams delivering some fractions of Gy. In such a dose range, the hypersensitivity to low dose (HRS) phenomenon can occur. HRS produces a biological effect equivalent to that produced by a dose 5-to-10 times higher. To examine whether HRS could contribute to enhancing radiation effects under SBRT conditions, we exposed tumor cells of different HRS statuses to SBRT. Four human HRS-positive and two HRS-negative tumor cell lines were exposed to different dose delivery modes: a single dose of 0.2 Gy, 2 Gy, 10 × 0.2 Gy, and a single dose of 2 Gy using a non-coplanar isocentric minibeams irradiation mode were delivered. Anti-γH2AXimmunofluorescence, assessing DNA double-strand breaks (DSB), was applied. In the HRS-positive cells, the DSB produced by 10 × 0.2 Gy and 2 Gy, delivered by tens of minibeams, appeared to be more severe, and they provided more highly damaged cells than in the HRS-negative cells, suggesting that more severe DSB are induced in the “SBRT modes” conditions when HRS occurs in tumor. Each SBRT session can be viewed as hyperfractionated dose delivery by means of hundreds of low dose minibeams. Under current SBRT conditions (i.e., low dose per minibeam and not using ultra-high dose-rate), the response of HRS-positive tumors to SBRT may be enhanced significantly. Interestingly, similar conclusions were reached with HRS-positive and HRS-negative untransformed fibroblast cell lines, suggesting that the HRS phenomenon may also impact the risk of post-RT tissue overreactions.
立体定向体部放疗（SBRT）使得高分次高剂量的治疗模式在少数几次治疗中更为可行。尽管大分割SBRT的获益常被归因于额外的血管效应、免疫效应或特定细胞死亡机制，但其放射生物学与机制模型仍需完善。在SBRT的每次治疗中，剂量被分解为数百个微束，每束携带数戈瑞的剂量。在此剂量范围内，可能出现低剂量超敏反应现象。该现象产生的生物学效应相当于常规剂量5至10倍的效果。为探究低剂量超敏反应是否可能增强SBRT条件下的放疗效果，我们将具有不同低剂量超敏反应状态的肿瘤细胞暴露于SBRT环境中。选用四种人源低剂量超敏反应阳性及两种阴性肿瘤细胞系，分别施以不同照射模式：单次0.2戈瑞、单次2戈瑞、10次×0.2戈瑞，以及采用非共面等中心微束照射模式的单次2戈瑞照射。通过抗γH2AX免疫荧光法评估DNA双链断裂水平。在低剂量超敏反应阳性细胞中，通过数十个微束实施的10次×0.2戈瑞与单次2戈瑞照射所产生的DNA双链断裂更为严重，且产生的高度损伤细胞多于低剂量超敏反应阴性细胞，提示当肿瘤发生低剂量超敏反应时，在“SBRT模式”条件下会诱导更严重的DNA双链断裂。每次SBRT治疗可视为通过数百个低剂量微束实施的大分割照射。在当前SBRT条件下（即每个微束剂量较低且未使用超高剂量率），低剂量超敏反应阳性肿瘤对SBRT的治疗响应可能显著增强。值得注意的是，在低剂量超敏反应阳性与阴性的未转化成纤维细胞系中也得出类似结论，这表明低剂量超敏反应现象可能同样影响放疗后组织过度反应的风险。
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