Flamant F, Rodary C, Rey A, Praquin M T, Sommelet D, Quintana E, Theobald S, Brunat-Mentigny M, Otten J, Voûte P A, Habrand J L, Martelli H, Barrett A, Terrier-Lacombe M J, Oberlin O
Institut Gustave-Roussy, Department of Paediatric Oncology, Villejuif, France.
Eur J Cancer. 1998 Jun;34(7):1050-62. doi: 10.1016/s0959-8049(98)00024-0.
The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.
第二届国际小儿肿瘤学会（SIOP）横纹肌肉瘤研究（MMT84）有多个目标。两个主要目的是：（1）提高横纹肌肉瘤患儿的生存率；（2）通过在初始化疗反应良好后限制手术和/或放疗的指征，减少治疗的晚期效应。另一个目的是研究大剂量化疗在患有脑膜旁原发性肿瘤的年轻患者中的作用。186名先前未接受过治疗的符合条件的患者进入了该研究。原发性肿瘤完全切除的患者接受三个疗程的IVA（异环磷酰胺、长春新碱和放线菌素D）。原发性肿瘤未完全切除的患者根据分期接受6至10个疗程的IVA。仅接受化疗即达到完全缓解的患者通常不接受放疗或进行广泛手术，但仍处于部分缓解的患者接受手术和/或放疗的局部治疗。只有5岁以上患有脑膜旁疾病的患者以及12岁以上任何部位患有肿瘤的患者接受系统性照射。所有患者中有91%（170/186）实现了完全缓解。中位随访8年，5年总生存率为68%（平均标准误差（SEM）为±3%），5年无事件生存率为53%（SEM为±4%）。这些结果表明，与之前的SIOP研究（RMS75）相比有改善，在RMS75研究中生存率为52%，无事件生存率为47%。在出现孤立局部复发的54例患者中，35%（19/54）在再次治疗（包括局部治疗（手术±放疗））后在进一步缓解中存活超过2年。对所有存活儿童接受的总体治疗负担（包括初始治疗以及必要时的复发治疗）进行分析表明，24%（28/116）接受了有限手术，随后进行三个疗程的IVA，29%（34/116）仅接受化疗（初始活检后），13%（15/116）接受化疗加保守局部治疗（对残留疾病进行有限手术或放疗）。只有34%（39/116）接受了定义为根治性广野放疗或根治性手术或两者的强化局部治疗。与之前SIOP研究的结果相比，MMT84的治疗基于对初始化疗的反应，尽管局部治疗的总体使用有所减少，但显著提高了非转移性疾病患者的生存率。该试验也是首次提供证据表明局部复发后再次治疗可实现长期二次缓解。
