Nelson D F, Curran W J, Scott C, Nelson J S, Weinstein A S, Ahmad K, Constine L S, Murray K, Powlis W D, Mohiuddin M
Department of Radiation Oncology, Highland Hospital of Rochester, NY 14620.
Int J Radiat Oncol Biol Phys. 1993 Jan 15;25(2):193-207. doi: 10.1016/0360-3016(93)90340-2.
Between January 1983 and November 1987, the Radiation Therapy Oncology Group conducted a prospective, randomized, multi-institutional, dose searching Phase I/II trial to evaluate hyperfractionated radiation therapy in the treatment of supratentorial malignant glioma. Patients with anaplastic astrocytoma, or glioblastoma multiforme, age 18-70 years with a Karnofsky performance status of 40-100 were stratified according to age, Karnofsky performance status, and histology, and were randomized. Initially randomization was to one of three arms: 64.8 Gy, 72.0 Gy, and 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week, with intervals of 4 to 8 hr. All patients received bis-chlorethyl nitrosourea (BCNU) 80 mg/m2 on days 3, 4, 5 of radiation therapy and then every 8 weeks for 1 year. After acceptable rates of acute and late effects were found, the randomization was changed to 81.6 Gy and 72.0 Gy with a weighting of 2:1. Out of 466 patients randomized, 435 were analyzed. The distribution of prognostic factors was comparable among the 76.8 Gy arm, 81.6 Gy arm, and the final randomization of the 72 Gy arm. The 64.8 Gy arm and the initial randomization of the 72 Gy arm had somewhat worse prognostic variables. Late radiation toxicity occurred in 1.3-6.8% of the patients, with a modest increase with increasing radiation dose. The best survival occurred in those patients treated with 72 Gy (median survival of 12.8 months overall, and 14 months for the final 72 Gy randomization). The Cox proportional hazards model confirmed the prognostic variables of age, histology and Karnofsky performance status. In addition, the longer interval of 4.5-8 hr was associated with a worse prognosis than the 4-4.4 hr interval (p = 0.0011). The difference in survival between the 81.6 Gy arm and the lower three arms approached significance (p = 0.078) with inferior survival observed in the 81.6 Gy arm. When therapy was evaluated by radiation therapy dose received (60-74.4 Gy compared with 74.5-84.0 Gy), the p value was 0.062 in favor of the lower dose range. Patients with anaplastic astrocytoma treated with 72 Gy by hyperfractionation + BCNU had at least as good a survival as those treated with 60 Gy by conventional fractionation + BCNU on Radiation Therapy Oncology Group protocols 7401 and 7918. This suggests that 72 Gy delivered by 1.2 Gy twice daily is no more toxic than 60 Gy delivered by conventional fractionation.
1983年1月至1987年11月期间，放射治疗肿瘤学组开展了一项前瞻性、随机、多机构、剂量探索性I/II期试验，以评估超分割放射治疗幕上恶性胶质瘤的效果。年龄在18 - 70岁、卡氏评分40 - 100的间变性星形细胞瘤或多形性胶质母细胞瘤患者，根据年龄、卡氏评分和组织学进行分层，然后随机分组。最初随机分为三组：64.8 Gy、72.0 Gy和76.8 Gy。每次给予1.2 Gy，每天两次，每周5天，间隔4至8小时。所有患者在放疗的第3、4、5天接受80 mg/m²的双氯乙基亚硝脲（BCNU）治疗，然后每8周一次，持续1年。在发现急性和晚期效应的可接受发生率后，随机分组改为81.6 Gy和72.0 Gy，权重为2:1。在随机分组的466例患者中，435例进行了分析。76.8 Gy组、81.6 Gy组和最终72 Gy组随机分组的预后因素分布具有可比性。64.8 Gy组和最初72 Gy组随机分组的预后变量稍差。1.3% - 6.8%的患者出现晚期放射毒性，且随着放射剂量增加有适度增加。接受72 Gy治疗的患者生存情况最佳（总体中位生存期为12.8个月，最终72 Gy随机分组的患者为14个月）。Cox比例风险模型证实了年龄、组织学和卡氏评分等预后变量。此外，4.5 - 8小时的较长间隔与4 - 4.4小时的间隔相比，预后更差（p = 0.0011）。81.6 Gy组与较低的三组之间的生存差异接近显著（p = 0.078），81.6 Gy组生存较差。当按接受的放射治疗剂量（60 - 74.4 Gy与74.5 - 84.0 Gy）评估治疗效果时，p值为0.062，支持较低剂量范围。根据放射治疗肿瘤学组7401和7918方案，采用超分割 + BCNU治疗72 Gy的间变性星形细胞瘤患者的生存情况至少与采用常规分割 + BCNU治疗60 Gy的患者一样好。这表明每天两次给予1.2 Gy的72 Gy剂量并不比常规分割给予60 Gy的毒性更大。
