Department of Neurosurgery, Haukeland University Hospital, 5021 Bergen, Norway ; Institute of Surgical Sciences, Haukeland University Hospital, 5021 Bergen, Norway ; Oncomatrix Research Lab, Department of Biomedicine, University of Bergen, 5021 Bergen, Norway.
Biomed Res Int. 2013;2013:139674. doi: 10.1155/2013/139674. Epub 2013 Nov 10.
Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs). However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS.
GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12 Gy or 18 Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test.
In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls (P < 0.001). In a second experiment, survival was 72 days in the treatment group versus 54 days in controls (P < 0.006). Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment (P = 0.04).
GKS administered with clinically relevant doses prolongs survival in rats harboring GBM xenografts, and the associated toxicity is mild.
伽玛刀手术（GKS）可用于治疗复发性胶质母细胞瘤（GBM）。然而，患者通常已经接受了多模式治疗，这使得很难将 GKS 与既定治疗方法分开进行专门验证。因此，我们开发了一种实验性脑肿瘤模型，以评估与 GKS 相关的疗效和放射性毒性。
将 GBM 异种移植物脑内植入裸鼠，并通过 MRI 确认移植。将大鼠分为 GKS 组，边缘剂量为 12 Gy 或 18 Gy，或不治疗。记录生存时间，检查肿瘤切片，并在行为开放场试验中评估放射性毒性。
在第一个系列中，从植入时间开始的生存时间在治疗组为 96 天，在对照组为 72 天（P < 0.001）。在第二个实验中，治疗组的生存时间为 72 天，对照组为 54 天（P < 0.006）。接受 GKS 的大鼠可见多核巨细胞和纤维化。在治疗后 4 周，未接受治疗的携带 GBM 异种移植物的大鼠在开放场测试中的移动性低于 GKS 治疗组（P = 0.04）。
以临床相关剂量给予 GKS 可延长携带 GBM 异种移植物的大鼠的生存时间，且相关毒性较轻。
