Zerbini C, Gelber R D, Weinberg D, Sallan S E, Barnes P, Kupsky W, Scott R M, Tarbell N J
Department of Pathology, Children's Hospital, Boston, MA 02115.
J Clin Oncol. 1993 Apr;11(4):616-22. doi: 10.1200/JCO.1993.11.4.616.
DNA ploidy status, completeness of surgical resection, use of chemotherapy, adequacy of radiation therapy, metastatic stage, sex, and age at diagnosis were evaluated as predictors of relapse in 58 patients with cerebellar medulloblastoma.
Flow cytometry (FCM) and/or image analysis (IA) were used to characterize tumor DNA ploidy. Twelve tumors (21%) were found to be aneuploid, 11 (19%) tetraploid, and 35 (60%) diploid.
The most significant predictors of relapse in univariate analyses were the adequacy of radiation (> or = 50 Gy) (P = .02), metastatic staging (P = .05), completeness of resection (P = .085), and DNA ploidy status (diploid/tetraploid v aneuploid; P = .11). When the 52 patients who received > or = 50 Gy were included in a multivariate Cox model analysis, those with diploid/tetraploid tumors had fewer recurrences than those with aneuploid tumors (relative risk, 0.33; 95% confidence interval, 0.12 to 0.89; P = .03). Patients with complete resections (P = .07), or with stage M0 disease (P = .06) had fewer recurrences than other patients, but these factors were not independent predictors of outcome. DNA ploidy status was correlated with age; 10 of the 12 aneuploid tumors were found in children ages 3 to 10 years. Age, sex, and the use of chemotherapy were not prognostically significant in these analyses.
The adequacy of radiation dose and DNA ploidy were the most important prognostic factors in this series. Contrary to previous reports, when corrected for adequacy of treatment, DNA aneuploidy was associated with a poor outcome. By multivariate analyses, DNA ploidy was an independent variable, even when controlling for extent of surgical resection and metastatic stage.
评估58例小脑髓母细胞瘤患者的DNA倍体状态、手术切除的完整性、化疗的使用、放射治疗的充分性、转移分期、性别及诊断时的年龄，以作为复发的预测因素。
采用流式细胞术（FCM）和/或图像分析（IA）对肿瘤DNA倍体进行特征分析。发现12例肿瘤（21%）为非整倍体，11例（19%）为四倍体，35例（60%）为二倍体。
单因素分析中，复发的最显著预测因素为放射治疗的充分性（≥50 Gy）（P = 0.02）、转移分期（P = 0.05）、切除的完整性（P = 0.085）及DNA倍体状态（二倍体/四倍体与非整倍体；P = 0.11）。当将接受≥50 Gy放射治疗的52例患者纳入多因素Cox模型分析时，二倍体/四倍体肿瘤患者的复发次数少于非整倍体肿瘤患者（相对危险度，0.33；95%可信区间，0.12至0.89；P = 0.03）。手术切除完整的患者（P = 0.07）或处于M0期疾病的患者（P = 0.06）的复发次数少于其他患者，但这些因素并非预后的独立预测因素。DNA倍体状态与年龄相关；12例非整倍体肿瘤中有10例见于3至10岁的儿童。在这些分析中，年龄、性别及化疗的使用在预后方面无显著意义。
在本系列研究中，放射剂量的充分性和DNA倍体是最重要的预后因素。与既往报道相反，校正治疗充分性后，DNA非整倍体与不良预后相关。通过多因素分析，即使在控制手术切除范围和转移分期的情况下，DNA倍体仍是一个独立变量。
