Cho Keun-Tae, Kim Dong Gyu, Paek Sun Ha, Chung Hyun-Tai, Jung Hee Won, Park Hyung Woo
Department of Neurosurgery, Dongguk University-Seoul and Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
J Neurol Surg A Cent Eur Neurosurg. 2012 May;73(3):132-41. doi: 10.1055/s-0032-1304216. Epub 2012 Apr 30.
Radiosurgery has been shown in a randomized trial not to provide any survival benefit for newly diagnosed glioblastoma multiforme (GBM). Nevertheless, several institutional retrospective series have supported the role of radiosurgery as an adjuvant therapy in GBM. The purpose of this study was to investigate the efficacy of concurrent therapy with 1,3 bis[2-chloroethyl]-1-nitrosourea (BCNU; carmustine) and Gamma Knife radiosurgery (GKRS; Gamma Knife® Model C, Elekta AB, Stockholm, Sweden) in the C6 rat glioma model. Taken together, new therapeutic strategies other than the simple addition of radiosurgery deserve to be investigated in the interest of enhancing the effects of radiosurgery.
C6 glioma cells of 5 × 105 were stereotactically implanted into Sprague-Dawley rats. Tumor volume was measured 2 weeks later using brain magnetic resonance (MR) imaging and rats were treated with BCNU (7 mg/kg, intraperitonial injection), GKRS (20 Gy at 50% isodose line), or BCNU followed by GKRS at a 1.5-hour interval. The six surviving rats in each group were sacrificed, 2 weeks after treatment. Tumor volume was measured in the tissue sections and compared with that measured via MR imaging. Percent volume growth was calculated and categorized into one of four groups: progressive disease, stable disease, partial response, or complete response.
Tumor volume significantly increased in all six rats in the control group and decreased in all six rats in the BCNU + GKRS group after treatment. Better tumor control was observed in the BCNU + GKRS group compared with the control, BCNU, and GKRS groups on linear-by-linear association analysis and Fischer's exact test.
We suggest that concurrent treatment with BCNU and GKRS is more effective in local tumor control compared with GKRS or BCNU alone, in the C6 rat glioma model.
一项随机试验表明，放射外科手术对新诊断的多形性胶质母细胞瘤（GBM）并无生存获益。然而，多个机构的回顾性系列研究支持放射外科手术作为GBM辅助治疗的作用。本研究的目的是在C6大鼠胶质瘤模型中研究1,3-双[2-氯乙基]-1-亚硝基脲（BCNU；卡莫司汀）与伽玛刀放射外科手术（GKRS；伽玛刀®C型，医科达公司，瑞典斯德哥尔摩）联合治疗的疗效。总体而言，为了增强放射外科手术的效果，除了单纯增加放射外科手术外，其他新的治疗策略值得研究。
将5×105个C6胶质瘤细胞立体定向植入Sprague-Dawley大鼠体内。2周后使用脑磁共振（MR）成像测量肿瘤体积，然后对大鼠进行BCNU（7mg/kg，腹腔注射）、GKRS（50%等剂量线处20Gy）治疗，或先注射BCNU，1.5小时间隔后再进行GKRS治疗。每组6只存活大鼠在治疗后2周处死。测量组织切片中的肿瘤体积，并与通过MR成像测量的结果进行比较。计算体积生长百分比，并分为四组之一：疾病进展、疾病稳定、部分缓解或完全缓解。
治疗后，对照组的6只大鼠肿瘤体积均显著增大，而BCNU+GKRS组的6只大鼠肿瘤体积均减小。在线性关联分析和费舍尔精确检验中，与对照组、BCNU组和GKRS组相比，BCNU+GKRS组的肿瘤控制效果更好。
我们认为，在C6大鼠胶质瘤模型中，与单独使用GKRS或BCNU相比，BCNU与GKRS联合治疗在局部肿瘤控制方面更有效。
