INTRINSIC RADIATION SENSITIVITY MAY NOT BE THE MAJOR DETERMINANT OF THE POOR CLINICAL OUTCOME OF GLIOBLASTOMA-MULTIFORME
INTRINSIC RADIATION SENSITIVITY MAY NOT BE THE MAJOR DETERMINANT OF THE POOR CLINICAL OUTCOME OF GLIOBLASTOMA-MULTIFORME
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DOI：
10.1016/0360-3016(93)90345-v
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发表时间：
1993-01-15
影响因子：
7
通讯作者：
SUIT, H
中科院分区：
文献类型：
--
作者：
TAGHIAN, A;RAMSAY, J;SUIT, H
目的：多种放射生物学机制可能与多形性胶质母细胞瘤的临床放射抵抗有关。其中之一被认为是异常低的本征辐射敏感性。这是一项由三个实验室联合开展的研究，旨在评估85个来自人类恶性胶质瘤的细胞系的本征辐射敏感性，这是这些肿瘤放射治疗临床效果不佳的主要原因。方法和材料：51个细胞系为早期传代细胞。按组织学类型分布：胶质母细胞瘤58例，间变性星形细胞瘤17例，少突胶质细胞瘤6例，星形细胞瘤2级4例。对生长在塑料上的指数期细胞系，在有氧条件下，测定了单次剂量辐照的SF2。结果：85个细胞系的SF2平均值为0.46(0.12~0.87)。按组织学类型划分，胶质母细胞瘤、间变性星形细胞瘤、少突胶质细胞瘤和星形细胞瘤2级细胞系的平均SF2分别为0.50、0.34、0.54和0.38。未发现SF2与患者年龄或卡诺夫斯基状态相关。58例胶质母细胞瘤和17例间变性星形细胞瘤细胞系sF2值差异有统计学意义(P=0.002)。胶质母细胞瘤和间变性星形细胞瘤患者的精算生存率差异有统计学意义(p=0.08)。两组患者来源的细胞系的SF2差异有统计学意义(p=0.08)。间变性星形细胞瘤和胶质母细胞瘤细胞系对辐射敏感性的差异清楚地反映在两组患者存活率的差异上。但未发现SF2与各级别的存活率之间存在相关性。在多因素分析中，年龄、分级和卡诺夫斯基状态是影响预后的重要因素，其p值分别为0.032、0.03和0.038，而sF2值则无统计学意义(p=0.4)。6株少突胶质细胞瘤细胞系的SF2平均值(0.54)与多形性胶质母细胞瘤的SF2平均值(0.50)相近。少突胶质细胞瘤的高SF2值并不符合这些肿瘤更好的临床结果。结论：85个恶性胶质瘤细胞系的这些数据显示了SF2值在体外非常广泛的辐射分布。SF2反映了AA(3年级)和GBM(4年级)的敏感度差异。这可能表明，SF2参数有助于区分不同级别或类型的体外组织学的敏感性。然而，SF2不能作为预测恶性胶质瘤个体临床预后的指标。体外研究需要补充体内肿瘤的生理特征。这些结论将限制目前基于体外剂量生存测量的放射敏感性分析对至少高级别恶性胶质瘤的预测价值。
Purpose: Many radiobiologic mechanisms may contribute to the clinical radiation resistance of Glioblastoma Multiforme. One of them is considered to be an unusually low intrinsic radiation sensitivity. This is a collaborative study between three laboratories to evaluate the intrinsic radiation sensitivity of 85 cell lines derived from human malignant gliomas as the major cause of the poor clinical results of radiation treatment to these tumors.Methods and Materials: Fifty-one cell lines were early passage. The distribution by histologic type was: 58 glioblastoma, 17 anaplastic astrocytoma, six oligodendroglioma and four astrocytoma grade 2. The intrinsic radiation sensitivity will be expressed by the surviving fraction at 2 Gy (SF2). The SF2 has been determined for single dose irradiation for cell lines on exponential phase, under aerobic conditions, growing on plastic. The patient age, Karnofski Status, histological grade, survival, dose of irradiation for 50 patients are investigated for correlation with SF2 Of the corresponding newly established cell lines.Results: The mean SF2 Of the 85 cell lines was 0.46 (0.12-0.87). The mean SF2 by histologic type was 0.50, 0.34, 0.54 and 0.38 for glioblastoma, anaplastic astrocytoma, oligodendroglioma and astrocytoma grade 2 cell lines, respectively. No correlation was found between SF2 and the patient age or Karnofski status. The difference in SF2 between the 58 glioblastoma and 17 anaplastic astrocytoma cell lines was significant p = 0.002. The difference in actuarial survival between glioblastoma and anaplastic astrocytoma patients was borderline of significance (p = 0.08). The difference in SF2 of cell lines derived from these two groups of patients was of borderline significance (p = 0.08). The difference in radiation sensitivity for anaplastic astrocytoma and glioblastoma cell lines was clearly reflected in the difference in survival for the two groups of patients from where the cell lines were derived. However, no correlation was found between SF2 and survival within each grade. In a multivariate analysis the age, grade and Karnofski status were found to be significant prognostic values for survival with a p values of 0.032, 0.03 and 0.038, respectively, however, the In SF2 was not significant (p = 0.40). The mean SF2 of the 6 oligodendroglioma cell lines (0.54) was comparable to that of glioblastoma multiforme (0.50). The high SF2 for oligodendroglioma does not accord with the much better clinical outcome of these tumors.Conclusions: These data on 85 malignant glioma cell lines show a very broad distribution of SF2 values for irradiation in vitro. SF2 reflected the difference in sensitivity between AA (Grade 3) and GBM (Grade 4). This may suggest that the parameter SF2 is useful to discriminate between the sensitivity of different grades or types of histology in vitro. However, SF2 was not a predictor of the clinical outcome on individual basis for malignant gliomas. The in vitro studies will need to be supplemented by physiologic characterization of the tumors in vivo. Such conclusions would limit the predictive value of current radiation sensitivity assays based on in vitro dose-survival measurement for at least high grade malignant gliomas.