Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States of America.
Department of Head and Neck Surgery & Communication Sciences, Duke University Medical Center, Durham, NC, United States of America.
Phys Med Biol. 2022 Feb 18;67(4). doi: 10.1088/1361-6560/ac508c.
. To develop and characterize novel methods of extreme spatially fractionated kV radiation therapy (including mini-GRID therapy) and to evaluate efficacy in the context of a pre-clinical mouse study.. Spatially fractionated GRIDs were precision-milled from 3 mm thick lead sheets compatible with mounting on a 225 kVp small animal irradiator (X-Rad). Three pencil-beam GRIDs created arrays of 1 mm diameter beams, and three 'bar' GRIDs created 1 × 20 mm rectangular fields. GRIDs projected 20 × 20 mmfields at isocenter, and beamlets were spaced at 1, 1.25, and 1.5 mm, respectively. Peak-to-valley ratios and dose distributions were evaluated with Gafchromic film. Syngeneic transplant tumors were induced by intramuscular injection of a soft tissue sarcoma cell line into the gastrocnemius muscle of C57BL/6 mice. Tumor-bearing mice were randomized to four groups: unirradiated control, conventional irradiation of entire tumor, GRID therapy, and hemi-irradiation (half-beam block, 50% tumor volume treated). All irradiated mice received a single fraction of 15 Gy.. High peak-to-valley ratios were achieved (bar GRIDs: 11.9 ± 0.9, 13.6 ± 0.4, 13.8 ± 0.5; pencil-beam GRIDs: 18.7 ± 0.6, 26.3 ± 1.5, 31.0 ± 3.3). Pencil-beam GRIDs could theoretically spare more intra-tumor immune cells than bar GRIDs, but they treat less tumor tissue (3%-4% versus 19%-23% area receiving 90% prescription, respectively). Bar GRID and hemi-irradiation treatments significantly delayed tumor growth ( < 0.05), but not as much as a conventional treatment ( < 0.001). No significant difference was found in tumor growth delay between GRID and hemi-irradiation.. High peak-to-valley ratios were achieved with kV grids: two-to-five times higher than values reported in literature for MV grids. GRID irradiation and hemi-irradiation delayed tumor growth, but neither was as effective as conventional whole tumor uniform dose treatment. Single fraction GRID therapy could not initiate an anti-cancer immune response strong enough to match conventional RT outcomes, but follow-up studies will evaluate the combination of mini-GRID with immune checkpoint blockade.
. 开发和表征新型极端空间分割千伏辐射治疗方法（包括微型网格治疗），并在临床前小鼠研究中评估其疗效。. 空间分割网格由 3 毫米厚的与 225 kVp 小动物辐照器（X-Rad）兼容的铅片精密铣削而成。三个铅笔束网格创建了直径为 1 毫米的光束阵列，三个“棒”网格创建了 1×20 毫米的矩形场。网格在等中心处投射 20×20 毫米的场，束斑分别间隔 1、1.25 和 1.5 毫米。使用 Gafchromic 胶片评估峰谷比和剂量分布。通过肌肉内注射软组织肉瘤细胞系到 C57BL/6 小鼠的比目鱼肌中诱导同源移植肿瘤。荷瘤小鼠随机分为四组：未照射对照组、整个肿瘤常规照射、网格治疗组和半照射（半束阻挡，50%肿瘤体积治疗）。所有照射的小鼠接受单次 15 Gy 照射。. 实现了高的峰谷比（棒状网格：11.9±0.9、13.6±0.4、13.8±0.5；铅笔束网格：18.7±0.6、26.3±1.5、31.0±3.3）。铅笔束网格理论上可以比棒状网格保留更多的肿瘤内免疫细胞，但它们治疗的肿瘤组织较少（分别为 3%-4%和 19%-23%的面积接受 90%的处方）。棒状网格和半照射治疗显著延迟肿瘤生长（<0.05），但不如常规治疗（<0.001）。网格和半照射治疗在肿瘤生长延迟方面没有发现显著差异。. 千伏网格实现了高的峰谷比：比文献中报道的 MV 网格高 2 到 5 倍。网格照射和半照射延迟肿瘤生长，但都不如常规全肿瘤均匀剂量治疗有效。单次分割网格治疗不能引发足够强烈的抗癌免疫反应来匹配常规 RT 结果，但后续研究将评估微型网格与免疫检查点阻断的联合应用。
