高剂量化疗与标准化疗和肺放疗联合治疗伴肺转移尤文肉瘤的疗效比较：来自欧洲尤文肿瘤国家协作组 99 试验和 EWING2008 试验的结果。
High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008.
机构信息
University Hospital Essen, Essen, Germany.
Royal Manchester Children's Hospital, Manchester, United Kingdom.
出版信息
J Clin Oncol. 2019 Dec 1;37(34):3192-3202. doi: 10.1200/JCO.19.00915. Epub 2019 Sep 25.
PURPOSE
The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases.
METHODS
From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and value were corrected for the three previous interim analyses by the inverse normal method.
RESULTS
Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm.
CONCLUSION
In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.
目的
R2Pulm 试验旨在评估与接受全身照射（WLI）的标准化疗相比，布美他尼-马法兰大剂量化疗联合自体干细胞解救（BuMel）方案在无肺照射（WLI）情况下对伴有肺和/或胸膜转移的尤因肉瘤（ES）患者的无事件生存（主要终点）和总生存的影响。
方法
2000 年至 2015 年，我们纳入了年龄小于 50 岁且初诊为 ES 且仅伴有肺或胸膜转移的患者。患者先接受六个疗程的长春新碱、异环磷酰胺、阿霉素和依托泊苷（VIDE）和一个疗程的长春新碱、放线菌素 D 和异环磷酰胺（VAI）治疗，然后按照随机分配接受 BuMel 或七疗程 VAI 和 WLI（VAI 加 WLI）治疗。分析采用意向治疗。采用逆正态法对前三次中期分析进行校正，得到风险比（HR）、95%CI 和 值的估计值。
结果
在 543 例潜在合格患者中，287 例患者被随机分配至 VAI 加 WLI（n = 143）或 BuMel（n = 144）组。为避免放疗与博来霉素相互作用引起的器官毒性过度，对需要进行轴性原发灶放疗的患者进行了排除，避免对其进行随机分组。中位随访时间为 8.1 年。我们未观察到两组患者生存结局有任何显著差异。VAI 加 WLI 和 BuMel 组患者 3 年时的无事件生存率分别为 50.6%和 56.6%，8 年时分别为 43.1%和 52.9%，VAI 加 WLI 和 BuMel 组的 HR 为 0.79（95%CI，0.56 至 1.10； =.16）。对于总生存率，HR 为 1.00（95%CI，0.70 至 1.44； =.99）。4 例患者死于博来霉素相关毒性，无患者死于 VAI 加 WLI 组。BuMel 组患者发生严重急性毒性反应的比例明显高于 VAI 加 WLI 组。
结论
对于伴有肺或胸膜转移的 ES 患者，与接受常规 VAI 加 WLI 相比，BuMel 方案并未带来明确获益。
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