Bauman G S, Ino Y, Ueki K, Zlatescu M C, Fisher B J, Macdonald D R, Stitt L, Louis D N, Cairncross J G
Department of Oncology, University of Western Ontario and London Regional Cancer Centre, London, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):825-30. doi: 10.1016/s0360-3016(00)00703-3.
Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients.
We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined.
Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004).
These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma.
1号染色体短臂的等位基因缺失可预测间变性少突胶质细胞瘤患者对化疗的影像学反应及较长的总生存时间。利用一个已知1号染色体短臂状态的少突胶质细胞瘤患者数据库，我们探讨了在放疗作为这些患者初始治疗一部分的情况下，1号染色体短臂的等位基因缺失是否也能预测更长的肿瘤控制持续时间。
我们测量了一组世界卫生组织（WHO）二级和WHO三级少突胶质细胞瘤患者放疗后的无进展生存期。通过单因素和多因素统计分析，研究了患者年龄、卡氏功能状态评分（KPS）、放疗时的肿瘤分级以及1号染色体短臂状态对无进展生存期的影响。对于新诊断的间变性少突胶质细胞瘤患者亚组，还研究了化疗的使用、1号染色体短臂状态与无进展生存期之间的关系。
55例患者（29例男性，26例女性；年龄18 - 75岁；中位数44岁；KPS 50 - 90，中位数80）因WHO二级（n = 19）或三级（n = 36）少突胶质细胞瘤接受放疗。28例患者在放疗前立即接受了化疗，27例在放疗后病情进展时接受了化疗。中位放射剂量为54 Gy，分30次给予。36个肿瘤中可见1号染色体短臂杂合性缺失（LOH），19个肿瘤中未见。放疗后的总体中位无进展生存期为40.4个月。肿瘤存在1号染色体短臂缺失的患者中位无进展生存期为55.0个月，而肿瘤保留1号染色体两个拷贝的患者中位无进展生存期为6.2个月（p < 0.001）。在单因素和多因素分析中，1号染色体短臂缺失都是二级和三级少突胶质细胞瘤患者无进展生存期延长的主要独立预测因素。对于三级少突胶质细胞瘤，化疗作为放疗的辅助手段可延长肿瘤存在1号染色体短臂等位基因缺失患者的肿瘤控制时间（p = 0.004）。
这些数据表明，少突胶质细胞瘤患者中1号染色体短臂的等位基因缺失可预测接受放疗±化疗作为初始治疗一部分的患者更长的无进展生存期。1号染色体短臂缺失可能是未来少突胶质细胞瘤治疗试验中的一个重要分层变量。
