Sullivan F J, Herscher L L, Cook J A, Smith J, Steinberg S M, Epstein A H, Oldfield E H, Goffman T E, Kinsella T J, Mitchell J B
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892.
Int J Radiat Oncol Biol Phys. 1994 Oct 15;30(3):583-90. doi: 10.1016/0360-3016(92)90944-d.
We report the outcome of a Phase II study of a cohort of patients with high-grade glioma treated with accelerated hyperfractionated radiation and the radiation sensitizer, iododeoxyuridine (IdUrd).
Between January 1988 and December 1990, 39 consecutive patients with high-grade glioma were enrolled and treated on a Phase II protocol including hyperfractionated radiation and IdUrd. Thirty-two patients were male and seven were female. Age range was 19 to 71 years with a median age of 38 years. IdUrd (1000 mg/m2 per day) was administered in two separate 14-day courses, the first during the initial radiation field and the second during the final cone-down field. All patients were treated consistently with partial brain technique and received 1.5 Gy/fraction twice daily to a mean total dose of 71.25 Gy (range 66-72 Gy excluding one patient who did not complete treatment). The initial field was treated to 45 Gy followed by a cone-down field covering the tumor volume plus a 1-cm margin to the final dose. Patients were assessed for acute and long-term morbidity and followed for outcome. Two patients had biopsies during the course of treatment. Flow cytometry and high performance liquid chromatography was used to evaluate the labeling index and the percent replacement of IdUrd in the biopsy specimen.
Thirty-eight of 39 patients completed therapy. One patient died on treatment at 48 Gy and is included in the survival analysis. No patient was lost to follow-up. Twenty-one patients had Grade 3 (anaplastic astrocytoma) tumors and 18 patients had Grade 4 (glioblastoma multiforme). Median survival for the entire cohort was 23 months. For the glioblastoma multiforme patients, median survival was 15 months. The median survival of the anaplastic astrocytoma patients has not yet been reached. In the patients assessed, the range of IdUrd tumor cell incorporation was only 0-2.4%.
Accelerated hyperfractionated radiation therapy with IdUrd was administered with acceptable acute toxicity. The major acute side effects of mucositis and thrombocytopenia were related to IdUrd infusion and were dose-dependent. There were no unacceptable acute toxicities referable to the radiation as delivered. With a median potential follow-up of 51 months, the actuarial median survival of the glioblastoma multiforme patients is comparable with the best previously published reports. The outcome of patients with anaplastic astrocytoma compares very favorably with even the most aggressive multi-modality approaches in the recent literature with a minimum of acute morbidity.
我们报告了一项II期研究的结果，该研究针对一组高级别胶质瘤患者，采用加速超分割放疗联合放疗增敏剂碘脱氧尿苷（IdUrd）进行治疗。
1988年1月至1990年12月期间，连续39例高级别胶质瘤患者入组并按照一项II期方案接受治疗，该方案包括超分割放疗和IdUrd。32例为男性，7例为女性。年龄范围为19至71岁，中位年龄为38岁。IdUrd（每日1000 mg/m²）分两个独立的14天疗程给药，第一个疗程在初始照射野期间，第二个疗程在最终缩野期间。所有患者均采用局部脑照射技术进行一致的治疗，每天两次，每次1.5 Gy，平均总剂量为71.25 Gy（范围66-72 Gy，不包括1例未完成治疗的患者）。初始照射野给予45 Gy，随后是缩野照射，覆盖肿瘤体积并外放1 cm至最终剂量。对患者进行急性和长期并发症评估，并随访预后。两名患者在治疗过程中进行了活检。采用流式细胞术和高效液相色谱法评估活检标本中IdUrd的标记指数和取代百分比。
39例患者中有38例完成治疗。1例患者在48 Gy治疗时死亡，并纳入生存分析。无患者失访。21例患者为3级（间变性星形细胞瘤）肿瘤，18例患者为4级（多形性胶质母细胞瘤）。整个队列的中位生存期为23个月。对于多形性胶质母细胞瘤患者，中位生存期为15个月。间变性星形细胞瘤患者的中位生存期尚未达到。在评估的患者中，IdUrd在肿瘤细胞中的掺入范围仅为0-2.4%。
加速超分割放疗联合IdUrd治疗的急性毒性可接受。粘膜炎和血小板减少等主要急性副作用与IdUrd输注有关，且呈剂量依赖性。所给予的放疗未出现不可接受的急性毒性。中位潜在随访时间为51个月，多形性胶质母细胞瘤患者的精算中位生存期与之前发表的最佳报告相当。间变性星形细胞瘤患者的预后与近期文献中最积极的多模式治疗方法相比非常有利，且急性并发症最少。
