Paulussen M, Ahrens S, Dunst J, Winkelmann W, Exner G U, Kotz R, Amann G, Dockhorn-Dworniczak B, Harms D, Müller-Weihrich S, Welte K, Kornhuber B, Janka-Schaub G, Göbel U, Treuner J, Voûte P A, Zoubek A, Gadner H, Jürgens H
Department of Pediatric Hematology/Oncology, University of Münster, Münster, Germany.
J Clin Oncol. 2001 Mar 15;19(6):1818-29. doi: 10.1200/JCO.2001.19.6.1818.
Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone.
We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models.
On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies.
Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.
合作尤因肉瘤研究（CESS）86旨在提高高危局限性骨尤因肿瘤患者的无事件生存率（EFS）。
我们分析了1986年1月至1991年7月招募的301例患者（60%为男性；中位年龄15岁）。肿瘤体积>100 mL和/或位于中轴线部位的患者符合“高危”（HR，n = 241）标准，而四肢小病灶患者为“标准风险”（SR，n = 52）。标准风险患者接受12个疗程的长春新碱、环磷酰胺和多柔比星与放线菌素D交替治疗（VACA）；高危患者用异环磷酰胺替代环磷酰胺（VAIA）。肿瘤部位为骨盆（27%）、其他中轴线部位（28%）、股骨（19%）或其他四肢部位（26%）。33%的病例初始肿瘤体积<100 mL，67%的病例初始肿瘤体积≥100 mL。局部治疗为手术（23%）、手术加放疗（49%）或单纯放疗（28%）。通过Kaplan-Meier分析估计无事件生存率，通过对数秩检验进行比较，并通过Cox模型分析危险因素。
1999年5月1日（研究中位时间为133个月），10年EFS为0.52。标准风险-VACA组（0.52）和高危-VAIA组（0.51，P = 0.92）的无事件生存率无差异。肿瘤体积>200 mL（EFS，0.36对比较小肿瘤的0.63；P = 0.0001）和组织学反应差（EFS，良好反应者为0.64对比0.38；P = 0.0007）对EFS有负面影响。在多因素分析中，肿瘤体积<200 mL、组织学反应良好和VAIA化疗预示着较好的预后。301例患者中有6例（2%）在治疗期间死亡，4例患者（1.3%）发生了第二原发恶性肿瘤。
CESS 86研究中52%的患者在接受风险适应性治疗后存活。高危患者似乎从包含异环磷酰胺的强化治疗中获益。
