背景:高危或转移性尤文肉瘤(ES)和横纹肌肉瘤(RMS)的患者预后良好。自体干细胞移植(ASCT)的大剂量化疗(HDT)已被评估为改善预后的治疗选择。然而,生存益处仍不清楚,治疗与严重的毒性有关。
方法:进行了系统评价,利用人口,干预,比较结果(PICO)模型,评估HDT/ASCT的使用是否会影响ES和RMS患者的预后,作为一线治疗的一部分或在复发情况下。Medline,Embase和CochraneCentral被问及1990年至2022年10月评估无事件生存(EFS)的出版物。总生存期(OS),和毒性。每个研究都由两名独立的审阅者筛选适合性。对结果进行定性合成。
结果:在筛选的1,172项独特研究中,41项研究符合纳入条件,29项研究考虑ES,10项研究考虑RMS,2项研究考虑两者。在VIDE化疗后接受HDT/ASCT的高危局部疾病ES患者中,以美法仑为基础的HDT/ASCT作为一线治疗的巩固,与标准化疗巩固相比,EFS和OS获益。使用VDC/IE主链的HDT/ASCT的功效,现在是标准护理,尚未建立。对于患有转移性疾病的ES患者,在初始诊断时未证实生存益处。对于复发性/难治性ES,4项回顾性研究报告HDT/ASCT结局改善,在HDT前出现治疗反应的患者中证据最大,以及14岁以下的患者。在RMS中,在原发性本地化的HDT/ASCT没有证实的生存益处,转移性或复发性疾病。
结论:需要前瞻性随机试验来确定HDT/ASCT在ES和RMS中的应用。选择患有复发性ES的患者可以考虑HDT/ASCT。
BACKGROUND: Patients with high-risk or metastatic Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) have a guarded prognosis. High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) has been evaluated as a treatment option to improve outcomes. However, survival benefits remain unclear, and treatment is associated with severe toxicities.
METHODS: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether utilization of HDT/ASCT impacts the outcome of patients with ES and RMS compared to standard chemotherapy alone, as part of first line treatment or in the relapse setting. Medline, Embase and Cochrane Central were queried for publications from 1990 to October 2022 that evaluated event-free survival (EFS), overall survival (OS), and toxicities. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed.
RESULTS: Of 1,172 unique studies screened, 41 studies were eligible for inclusion with 29 studies considering ES, 10 studies considering RMS and 2 studies considering both. In ES patients with high-risk localised disease who received HDT/ASCT after VIDE chemotherapy, consolidation with melphalan-based HDT/ASCT as first line therapy conveyed an EFS and OS benefit over standard chemotherapy consolidation. Efficacy of HDT/ASCT using a VDC/IE backbone, which is now standard care, has not been established. Survival benefits are not confirmed for ES patients with metastatic disease at initial diagnosis. For relapsed/refractory ES, four retrospective studies report improvement in outcomes with HDT/ASCT with the greatest evidence in patients who demonstrate a treatment response before HDT, and in patients under the age of 14. In RMS, there is no proven survival benefit of HDT/ASCT in primary localised, metastatic or relapsed disease.
CONCLUSIONS: Prospective randomised trials are required to determine the utility of HDT/ASCT in ES and RMS. Selected patients with relapsed ES could be considered for HDT/ASCT.