Koscielniak Ewa, Blank Bernd, Vokuhl Christian, Kazanowska Bernarda, Ladenstein Ruth, Niggli Felix, Ljungman Gustaf, Handgretinger Rupert, Seitz Guido, Fuchs Jörg, Fröhlich Birgit, Scheer Monika, Wessalowski Rüdiger, Schmid Irene, Sparber-Sauer Monika, Klingebiel Thomas
Pediatrics 5 (Oncology, Hematology, Immunology), Klinikum Stuttgart-Olgahospital, 70174 Stuttgart, Germany.
Faculty of medicine, University of Tübingen, 72016 Tübingen, Germany.
Cancers (Basel). 2022 Feb 11;14(4):899. doi: 10.3390/cancers14040899.
We report here the results of the prospective, non-randomized, historically controlled CWS-2002P study in patients ≤ 21 years with localized RMS developed with the aim to improve the long-term outcome by adapting the burden of therapy to risk profile and to investigate the feasibility and relation to the outcome of maintenance therapy (MT) in the high-risk groups. Patients were allocated into low-risk (LR), standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. Chemotherapy consisted of vincristine (VCR) and dactinomycin (ACTO-D) for all patients with the addition of ifosfamide (IFO) in the SR, HR, and VHR and doxorubicin (DOX) in the HR and VHR groups. Low-dose cyclophosphamide and vinblastine maintenance therapy (MT) over 6 months was recommended in the HR and VHR groups. A total of 444 patients have been included in this analysis. With a median follow-up of 9·6 years (IQR 7·6-10·9) for patients alive, the 5-year EFS and OS for the whole group was 73% (95% CI 69-77) and 80% (95% CI 76-84), respectively. The 5-year EFS by risk group was 100% in the LR, 79% (95% CI 72-84) in the SR, 69% (95% CI 63-75) in the HR, and 42% (95% CI 23-61) in the VHR (log-rank = 0.000). The 5-year EFS was 77% (95% CI 70-84) for 155 patients in the HR group who received MT as compared to 63% (95% CI 50-76) for 49 patients who did not (log-rank = 0.015). Neither the reduction in the IFO dose in the SR nor the increased dose intensity of DOX in HR groups influenced the outcome when compared to the previous CWS and other European studies. MT was feasible, seemed to have an impact on prognosis, and should be studied in a well-controlled prospective trial in this patient population. The weighting of risk factors used for therapy stratification needs to be reevaluated.
我们在此报告前瞻性、非随机、历史对照的CWS - 2002P研究结果，该研究针对年龄≤21岁的局限性横纹肌肉瘤患者开展，旨在通过根据风险状况调整治疗负担来改善长期预后，并研究高危组维持治疗（MT）的可行性及其与预后的关系。患者被分为低危（LR）、中危（SR）、高危（HR）和极高危（VHR）组。所有患者的化疗方案均包含长春新碱（VCR）和放线菌素D（ACTO - D），中危、高危和极高危组在此基础上加用异环磷酰胺（IFO），高危和极高危组再加用阿霉素（DOX）。高危和极高危组推荐进行为期6个月的低剂量环磷酰胺和长春碱维持治疗（MT）。本分析共纳入444例患者。存活患者的中位随访时间为9.6年（四分位间距7.6 - 10.9年），全组5年无事件生存率（EFS）和总生存率（OS）分别为73%（95%置信区间69 - 77）和80%（95%置信区间76 - 84）。各风险组的5年EFS分别为：低危组100%，中危组79%（95%置信区间72 - 84），高危组69%（95%置信区间63 - 75），极高危组42%（95%置信区间23 - 61）（对数秩检验P = 0.000）。高危组中接受MT的155例患者的5年EFS为77%（95%置信区间70 - 84），未接受MT的49例患者为63%（95%置信区间50 - 76）（对数秩检验P = 0.015）。与之前的CWS研究及其他欧洲研究相比，中危组IFO剂量的减少和高危组DOX剂量强度的增加均未影响预后结果。MT是可行的，似乎对预后有影响，应在该患者群体中开展严格对照的前瞻性试验进行研究。用于治疗分层的风险因素权重需要重新评估。
