Linskey M E, Martinez A J, Kondziolka D, Flickinger J C, Maitz A H, Whiteside T, Lunsford L D
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pennsylvania.
J Neurosurg. 1993 Apr;78(4):645-53. doi: 10.3171/jns.1993.78.4.0645.
An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.
采用将肿瘤异种移植到无胸腺（裸）小鼠肾被膜下的实验模型，来评估人类听神经瘤对立体定向放射外科手术的早期反应。在植入异种移植物后，45只小鼠使用201源60钴伽马装置（4毫米准直器、单等中心、80%等剂量线）接受了单次剂量为10、20或40 Gy的放射外科手术。将45个接受放射外科治疗的异种移植物与15个未治疗的异种移植物以及15个接受“假放射外科手术”的小鼠体内的异种移植物进行比较。所有五个研究组在以下预处理变量方面进行了匹配：肿瘤来源患者、动物体重、异种移植物平均直径以及异种移植物表面血管化百分比。在处死小鼠之前，立即对所有异种移植物进行原位评估，以确定平均肿瘤直径、肿瘤体积和表面血管化百分比。在放射外科手术后2周、1个月或3个月处死小鼠。由一名独立的神经病理学家进行盲法组织学检查。在40 Gy放射外科手术组中，术后2周肿瘤体积缩小了33.6%（p = 0.023），3个月后缩小了45%（p = 0.018）。在20 Gy放射外科手术组中，术后1个月肿瘤体积缩小了46.2%（p = 0.0002），3个月后缩小了35.2%（p = 0.032）。在10 Gy放射外科手术组中，术后3个月观察到平均体积缩小了16.4%（p = 0.17）。术后3个月时，40 Gy放射外科手术组肿瘤表面血管化平均减少了19.7%（p = 0.043），20 Gy放射外科手术组减少了5.8%（p = 0.12），10 Gy放射外科手术组和两个对照组均无变化。组织学检查显示，与对照组相比，放射外科手术异种移植物中铁蛋白沉积（p = 0.026）和血管壁玻璃样变（p = 0.032）的发生率更高。裸鼠肾被膜下异种移植是研究放射外科手术后听神经瘤体内放射生物学的极佳模型。细胞和血管效应均可在原位进行连续评估，且该模型即使在移植后4个月仍保持稳定。有必要进行进一步研究，在更接近临床神经影像学变化时间进程（6至12个月）的时间段内研究放射生物学。
