Sheehan Jason, Ionescu Adina, Pouratian Nader, Hamilton D Kojo, Schlesinger David, Oskouian Rod J, Sansur Charles
Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA.
J Neurosurg. 2008 May;108(5):972-8. doi: 10.3171/JNS/2008/108/5/0972.
Adjuvant treatment with radiation (radiation therapy or radiosurgery) is a mainstay of treatment for patients harboring glioblastomas multiforme (GBM). Hypoxic regions within the tumor make cells less sensitive to radiation therapy. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion in the brain and elevate the partial brain oxygen level. The goal of this study was to evaluate the radiosensitizing effects of TSC on GBM tumors.
A rat C6 glioma model was used, in which C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Following creation of a right frontal tumor, animals were randomized into 1 of 4 groups: 1) TSC alone (animal treated with moderate-dose TSC only); 2) radiation (animals receiving 8 Gy of cranial radiation); 3) radiation and low-dose TSC (animals receiving 8 Gy of radiation and 50 microg/kg of TSC); or 4) radiation and moderate-dose TSC (animals receiving 8 Gy of radiation and 100 microg/kg of TSC). Animals were observed clinically for 60 days or until death. Magnetic resonance (MR) imaging was performed at 2-week intervals on each animal and quantitatively evaluated for tumor response. Immunohistochemical analysis was performed on all brain tumors. Survival differences were also evaluated using the Kaplan-Meier method.
On MR imaging, a statistically significant reduction in tumor size was seen in the group receiving moderate-dose TSC and radiation treatment compared with the group receiving radiation treatment alone. The rate of tumor growth was significantly less for the combination of TSC and radiation treatment compared with either modality alone. Median survival times for the TSC-only and the radiation therapy-only groups were 15 and 30 days, respectively. The 60-day median survival times for the groups receiving a combination of either low- or moderate-dose TSC with radiation therapy were statistically improved compared with those for the other treatment groups.
Use of TSC improves the extent of GBM tumor regression following radiation therapy and enhances survival. Radiosensitization of hypoxic tumors through increased oxygen diffusion may have clinical utility in patients with GBM tumors but must be explored in a clinical trial.
辅助放疗（放射治疗或立体定向放射外科治疗）是多形性胶质母细胞瘤（GBM）患者的主要治疗手段。肿瘤内的缺氧区域会使细胞对放射治疗的敏感性降低。反式 crocetinate 钠（TSC）已被证明可增加大脑中的氧扩散并提高脑局部氧水平。本研究的目的是评估 TSC 对 GBM 肿瘤的放射增敏作用。
使用大鼠 C6 胶质瘤模型，将 C6 胶质瘤细胞立体定向注射到大鼠脑内以形成肿瘤。在形成右侧额叶肿瘤后，将动物随机分为 4 组中的 1 组：1）单独使用 TSC（仅用中等剂量 TSC 治疗的动物）；2）放疗（接受 8 Gy 颅脑照射的动物）；3）放疗加低剂量 TSC（接受 8 Gy 放疗和 50 μg/kg TSC 的动物）；或 4）放疗加中等剂量 TSC（接受 8 Gy 放疗和 100 μg/kg TSC 的动物）。对动物进行 60 天的临床观察或直至死亡。每隔 2 周对每只动物进行磁共振（MR）成像，并对肿瘤反应进行定量评估。对所有脑肿瘤进行免疫组织化学分析。还使用 Kaplan-Meier 方法评估生存差异。
在 MR 成像上，与单纯接受放疗的组相比，接受中等剂量 TSC 和放疗的组肿瘤大小有统计学意义的减小。与单独使用任何一种治疗方式相比，TSC 和放疗联合治疗的肿瘤生长速率明显更低。仅使用 TSC 组和仅使用放射治疗组的中位生存时间分别为 15 天和 30 天。与其他治疗组相比，接受低剂量或中等剂量 TSC 与放疗联合治疗组的 60 天中位生存时间在统计学上有改善。
使用 TSC 可提高放疗后 GBM 肿瘤的消退程度并延长生存期。通过增加氧扩散对缺氧肿瘤进行放射增敏可能对 GBM 肿瘤患者具有临床应用价值，但必须在临床试验中进行探索。
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