Dunst J, Jürgens H, Sauer R, Pape H, Paulussen M, Winkelmann W, Rübe C
Department of Radiotherapy, University of Halle, Germany.
Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):919-30. doi: 10.1016/0360-3016(95)00016-r.
We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86.
From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk (extremity tumors < 100 cm3), or vincristine, actinomycin D, ifosfamide, and adriamycin (VAIA) in high-risk tumors (central tumors and extremity tumors > or = 100 cm3). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for conventional fractionation). For quality assurance in radiotherapy, a central treatment planning program was part of the protocol.
Forty-four patients (25%) received definitive radiotherapy; 39 (22%) had surgery, and 93 (53%) had resection plus postoperative irradiation. The overall 5-year survival was 69%. Thirty-one percent of the patients relapsed, 30% after radiotherapy, 26% after radical surgery, and 34% after combined local treatment. The better local control after radical surgery (100%) and resection plus radiotherapy (95%) as compared to definitive radiotherapy (86%) was not associated with an improvement in relapse-free or overall survival because of a higher frequency of distant metastases after surgery (26% vs. 29% vs. 16%). In irradiated patients, hyperfractionated split-course irradiation and conventional fractionation yielded the same results (5-year overall survival of definitively irradiated patients 63% after conventional fractionation and 65% after hyperfractionation; relapse-free survival 53% vs. 58%; local control 76% vs. 86%, not significant). The six local failures after radiotherapy did not correlate with tumor size or response to chemotherapy. Radiation treatment quality (target volume, technique, dosage) was evaluated retrospectively and was scored as unacceptable in only 1 out of 44 patients (2%) with definitive radiotherapy. Grade 3-4 complications developed in 4 out of 44 (9%) patients after definitive radiotherapy.
Under the given selection criteria for local therapy, radiation therapy yielded relapse-free and overall survival figures comparable to radical surgery. Hyperfractionated split-course irradiation simultaneously with multidrug chemotherapy did not significantly improve local control or survival.
我们对多机构尤因肉瘤研究CESS 86进行了更新分析。
从1986年1月至1991年6月，招募了177例25岁及以下的局限性骨尤因肉瘤患者。化疗方案为：低风险（肢体肿瘤<100 cm³）患者接受四个为期9周的长春新碱、放线菌素D、环磷酰胺和阿霉素（VACA）疗程；高风险肿瘤（中央肿瘤和肢体肿瘤≥100 cm³）患者接受长春新碱、放线菌素D、异环磷酰胺和阿霉素（VAIA）疗程。局部治疗由每位患者单独决定，包括根治性手术（截肢、广泛切除）或切除加术后45 Gy放疗或60 Gy（45 Gy加增敏）的根治性放疗。接受放疗的患者在分割方式上随机分组，分为常规分割（每日一次1.8 - 2.0 Gy，化疗中断）或与VACA/VAIA化疗同时进行的超分割分段放疗（每日两次1.6 Gy，在22.4 Gy和44.8 Gy后休息12天，总剂量和治疗时间与常规分割相同）。为确保放疗质量，方案中包含一个中央治疗计划程序。
44例（25%）患者接受了根治性放疗；39例（22%）进行了手术，93例（53%）进行了切除加术后放疗。总体5年生存率为69%。31%的患者复发，放疗后复发率为30%，根治性手术后为26%，联合局部治疗后为34%。根治性手术（100%）和切除加放疗（95%）后的局部控制效果优于根治性放疗（86%），但由于手术后远处转移频率较高（分别为26%、29%和16%），无复发生存率或总生存率并未得到改善。在接受放疗的患者中，超分割分段放疗和常规分割的结果相同（接受根治性放疗患者的5年总生存率，常规分割后为63%，超分割后为65%；无复发生存率分别为53%和58%；局部控制率分别为76%和86%，差异无统计学意义）。放疗后的6例局部失败与肿瘤大小或化疗反应无关。对放疗质量（靶区体积、技术、剂量）进行了回顾性评估，在44例接受根治性放疗的患者中，只有1例（2%）的评分不可接受。44例（9%）接受根治性放疗的患者中有4例出现3 - 4级并发症。
在给定的局部治疗选择标准下，放射治疗的无复发生存率和总生存率与根治性手术相当。与多药化疗同时进行的超分割分段放疗并未显著改善局部控制或生存率。
