The intergroup rhabdomyosarcoma study.A preliminary report (original) (raw)
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International Journal of Oncology, 1995
To avoid the delayed consequences of treatment with radiotherapy, an effort was made to determine if patients with rhabdomyosarcoma could be cured with chemotherapy as the sole form of treatment. Alternatively, if radiotherapy and/or surgery were required to reduce the severity and incidence of delayed sequelae, an effort was made to determine if there was an optimum safe period for delaying implementation of these definitive forms of treatment. In patients where primary (immediate) definitive non-mutilating surgical extirpation of tumor was not feasible, exclusive treatment with chemotherapy was implemented. If considered necessary or appropriate, delayed surgery and/or radiation therapy were employed in 3 circumstances: (i) to consolidate a partial response; (ii) failure to respond; (iii) recurrent disease. The outcome of the delays prior to the implementation of definitive therapy was analyzed as a function of local and systemic recurrence and cure. Fifty-two patients were evaluated. Seven underwent primary nonmutilating surgical extirpation of localized tumor followed by adjuvant chemotherapy. The remaining 45 were treated with primary chemotherapy and 44 responded. Actuarial survival curves of the delay in initiating definitive therapy in the 52 patients revealed that the optimum delay to attain the best survival was 5 months. In circumstances where definitive therapy was not electively introduced, recurrent disease during remission appeared between 7 and 14 months in 7 patients on continued treatment, and in one patient at 30 months, 8 months after discontinuation of chemotherapy. Based upon the 5-month delay an analysis of survival was
Journal of the Egyptian National Cancer Institute, 2006
Our present study is a retrospective analysis of the treatment results of new rhabdomyosarcoma pediatric patients who had attended the pediatric unit clinic of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK) from January 1992 to January 2001). Fifty-five new cases of pediatric rhabdomyosarcoma attended the pediatric unit outpatient clinic of (NEMROCK) from the period of January 1992 until January 2001. Patients were divided into 4 stages and classified into low-risk patients and high-risk patients according to the extent of resection. Stage I, II orbital and stage I para-testicular embryonal rhabdomyosarcomas received 32 weeks of vincristine and actinomycin- D (vincristine 1.5 mg/m2 weekly, actinomycin-D 0.015 mg/Kg/day day 1 to day 5). Other pathologies, sites and stages received 52 weeks of chemotherapy. Chemotherapy regimens included VAC (vincristine 1.5 mg/m2 weekly, actinomycin-D 0.015 mg/Kg/day day 1 to day 5 and endoxan 2.2 gm/m2 I.V with mesna every ...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
Patients with metastatic rhabdomyosarcoma (RMS), except those younger than 10 years with embryonal RMS, have an estimated long-term event-free survival (EFS) of less than 20%. The main goal of this study was to improve outcome of patients with metastatic RMS by dose intensification with interval compression, use of the most active agents determined in phase II window studies, and use of irinotecan as a radiation sensitizer. Patients with metastatic RMS received 54 weeks of therapy: blocks of therapy with vincristine/irinotecan (weeks 1 to 6, 20 to 25, and 47 to 52), interval compression with vincristine/doxorubicin/cyclophosphamide alternating with etoposide/ifosfamide (weeks 7 to 19 and 26 to 34), and vincristine/dactinomycin/cyclophosphamide (weeks 38 to 46). Radiation therapy occurred at weeks 20 to 25 (primary) but was also permitted at weeks 1 to 6 (for intracranial or paraspinal extension) and weeks 47 to 52 (for extensive metastatic sites). One hundred nine eligible patients ...
Radiotherapy and Oncology, 1985
This therapeutic trial deals with 81 patients with stage III rhabdomyosarcoma (RMS), from different centers of the International Society of Pediatric Oncology. These patients were included between October 1975 and March 1983. The aim of this work is to minimize the sequelae of treatment without jeopardizing the survival rate. After a pretrial course of VAC, two groups of patients are compared: the first treated with systematic extensive surgery or radiotherapy on the initial tumor volume, and the second treated with combined chemotherapy using vincristine, dactinomycin, adriamycin, cyclophosphamide until maximum tumor reduction, followed by radiotherapy or surgery on the residual mass only. Eighty one patients were included in the trial; 15 patients were not randomized due to the failure of the pretrial course of chemotherapy, 3 were excluded after randomization (2 were found not to have RMS, and in one case the protocol was not observed). The preliminary results for the 63 patients show a survival rate of 40% at 3 years. The sequential scheme for patients at 3 years follow-up does not show a superiority in either arm.
International Journal of Radiation Oncology*Biology*Physics, 2000
To evaluate the outcome and toxicity of hyperfractionated radiotherapy (HFRT) vs. conventionally fractionated radiotherapy (CFRT) in children with Group III rhabdomyosarcoma (RMS). Five hundred fifty-nine children were enrolled into the Intergroup Rhabdomyosarcoma Study IV with Group III RMS. Sixty-nine were ineligible for the analysis because of incorrect group or pathologic findings. Of the 490 remaining, 239 were randomized to HFRT (59.4 Gy in 54 1.1-Gy twice daily fractions) and 251 to CFRT (50.4 Gy in 28 1.8-Gy daily fractions). The age range was <1-21 years. All patients received chemotherapy. RT began at Week 9 after induction chemotherapy for all but those with high-risk parameningeal tumors who received RT during induction chemotherapy. The patient groups were equally balanced. The median follow-up was 3.9 years. Analysis by randomized treatment assignment (intent to treat) revealed an estimated 5-year failure-free survival (FFS) rate of 70% and overall survival (OS) of 75%. In the univariate analysis, the factors associated with the best outcome were age 1-9 years at diagnosis; noninvasive tumors; tumor size <5 cm; uninvolved lymph nodes; Stage 1 or 2 disease; primary site in the orbit or head and neck; and embryonal histologic features (p = 0.001 for all factors). No differences in the FFS or OS between the two RT treatment methods and no differences in the FFS or OS between HFRT and CFRT were found when analyzed by age, gender, tumor size, tumor invasiveness, nodal status, histologic features, stage, or primary site. Treatment compliance differed by age. Of the children <5 years, 57% assigned to HFRT received HFRT and 77% assigned to CFRT received CFRT. Of the children >or=5 years, 88% assigned to both HFRT and CFRT received their assigned treatment. The reasons for not receiving the appropriate randomized treatment were progressive disease, early death, parent or physician refusal, young age, or surgery. The toxicity assessment revealed more mucositis with HFRT (66%) than with CFRT (46%) (p = 0.03) for the parameningeal patients, and more skin reactions (16%) and nausea/vomiting (13%) with HFRT than with CFRT (7% and 5%, respectively) for patients with nonparameningeal primary tumors (p = 0.03 and p = 0.02, respectively). The analysis by treatment actually received revealed a 5-year FFS rate of 73% and OS rate of 77%, with no difference between CFRT and HFRT. As well, there was no difference in FFS or OS between CFRT and HFRT when analyzed by age, gender, tumor size, tumor invasiveness, modal status, histology, stage or site of primary. The 5-year estimated cumulative incidence of failure for the irradiated patients was local, 13%; regional, 3%; and distant, 13%; with no differences between HFRT and CFRT. The 5-year local failure rate by site was orbit, 5%; head and neck, 12%; parameningeal, 16%; bladder/prostate, 19%; extremity, 7%; and all others, 14%. The 5-year regional failure rate was parameningeal,1%; extremity, 20%; and all others, 5%. The 5-year distant failure rate was orbit, 2%; head and neck, 6%; parameningeal, 11%; bladder/prostate, 15%; extremity, 28%; and all others, 17%. HFRT, as given in this study, did not improve local/regional control, FFS, or OS compared with CFRT. The risk of local/regional failure was comparable to that of distant failure in children with Group III RMS. The standard of care for Group III RMS continues to be CFRT with chemotherapy.
Cancers, 2022
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) ...
European Journal of Cancer, 2007
To evaluate the local control rates and survival rates of patients with Group III parameningeal rhabdomyosarcoma (PM-RMS) treated with a dose intensive chemotherapy regimen followed by irradiation. Materials and methods: Twenty-six patients with group III, PM-RMS were enrolled in a prospective pilot trial at the Mayo Clinic, Rochester, MN and Children's Hospital and Regional Medical Center Seattle, WA. The median age at diagnosis was 8.5 years (range 1.5-19 years). The male to female patient ratio was 1.6:1. Twenty-three patients had embryonal histology with the remaining three alveolar. Risk factors indicating high risk disease included intracranial extension (10 patients), base of skull erosion (12 patients), and cranial nerve palsy (10 patients). The median follow-up period for all patients was 82 months (range 17-148 months). Patients were treated with an intensified chemotherapy regimen followed by definitive local irradiation at week 12 following further chemotherapy. The median time from initiation of chemotherapy to irradiation was 16 weeks (range 6-23). The median dose delivered was 50.4 Gy (50.4-66.6 Gy). Results: Response was assessed after the fourth course of chemotherapy. Three patients exhibited a complete response, 22 a partial response, and 1 patient had no response after two cycles of chemotherapy and proceeded to irradiation at week 6. The 5-year estimated event free survival was 81% (±15%, 95% CI). Two patients died from progressive metastatic disease; 1 patient died from secondary malignancy; and 2 patients died from locally progressive disease. The 5-year local control rate was 92% (±10.6%, 95% CI). Conclusions: Treatment of group III PM-RMS patients with neo-adjuvant, intensive chemotherapy with a delay in irradiation resulted in excellent local-regional control rates and survival rates and may allow for a response-based radiotherapy approach.
European Journal of Cancer, 1998
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 eVects 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 de®ned as radical wide ®eld 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, signi®cantly improved survival for patients with non-metastatic disease. This trial, also for the ®rst time, provides evidence that retreatment after local relapse can achieve long-term second remissions.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018
Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided α-level) to detect an improved lon...