TREATMENT OF NONMETASTATIC RHABDOMYOSARCOMAS IN CHILDHOOD AND ADOLESCENCE - RESULTS OF THE 2ND STUDY OF THE INTERNATIONAL-SOCIETY-OF-PEDIATRIC-ONCOLOGY - MMT84

The second International Society of Paediatric Oncology (SIOP) study f or rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; a nd (2) to reduce the late effects from therapy by restricting the indi cations 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 wi th completely resected primary tumour received three courses of IVA (i fosfamide, 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 patient s remaining in partial remission received local therapy with surgery a nd/or radiotherapy. Only patients over 5 years of age with parameninge al disease and patients over 12 years with tumours at any site were gi ven systematic irradiation. Complete remission was achieved in 91% (17 0/186) 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)) an d 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 exhibit ed isolated local relapse, 35% (19/54) survived in further remission l onger 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 Limi ted surgery followed by three courses of IVA, 29% (34/116) were treate d by chemotherapy alone (after initial biopsy) and 13% (15/116) receiv ed chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensi ve local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous S IOP study, treatment in MMT84 was based on response to initial chemoth erapy and, despite an overall reduction of the use of local therapy, s ignificantly improved survival for patients with non-metastatic diseas e. This trial, also for the first time, provides evidence that retreat ment after local relapse can achieve long-term second remissions. (C) 1998 Elsevier Science Ltd. All rights reserved.