Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84.

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.

Value of postchemotherapy bioptical verification of complete clinical remission in previously incompletely resected (stage I and II pT3) malignant mesenchymal tumors in children: International Society of Pediatric Oncology 1984 Malignant Mesenchymal Tumors Study.

Bioptical verification of complete clinical remission achieved with postoperative chemotherapy in 140 pediatric patients with nonradically resected stages I and II nonparameningeal malignant mesenchymal tumors was evaluated. Tumor histology was rhabdomyosarcoma in 92 and nonrhabdomyosarcoma in 48 patients. All were included in the International Society of Pediatric Oncology "1984 Malignant Mesenchymal Tumors Study." Treatment given after nonradical surgery and before the biopsy consisted of 3 to 6 IVA courses (ifosfamide, vincristine, actinomycin D). Complete clinical remission (no tumor at physical examination, X-rays, sonography, computed tomography, scintigraphy) was bioptically confirmed in 52 rhabdomyosarcoma and 23 nonrhabdomyosarcoma cases, whereas in all the remaining patients (39 rhabdomyosarcoma and 22 nonrhabdomyosarcoma) complete clinical remission was not bioptically verified. Forty-eight-month local relapse rates were 51% in bioptically confirmed and 48% in nonbiopsied rhabdomyosarcoma patients. In nonrhabdomyosarcoma cases, relapse rates were 25% and 14%, respectively. In 4 cases, bioptical specimens contained tumor cells. In spite of aggressive treatment, only 1 is actually in remission. The total 48-month relapse rate (biopsied and nonbiopsied) was significantly higher in rhabdomyosarcoma patients (50%) than in nonrhabdomyosarcoma patients (26%). The value of bioptical verification of complete clinical remission seems to be limited in our series, when known that relapse rate in bioptically confirmed complete remission cases remained high and the outcome in rare "positive biopsy patients" was poor.