Local therapy is critical in localised pelvic rhabdomyosarcoma: Experience of the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT) committee

Purpose To describe the outcome of infants with a histologically confirmed diagnosis of malignant mesenchymal tumor (MMT) included in the International Society of Paediatric Oncology studies MMT 84 and MMT 89. Patients and Methods One hundred two infants (≤ 12 months old) were included. Twenty-four children were less than 3 months old, and 16 were less than 1 month old. Sixty-four patients had rhabdomyosarcoma (RMS), 26 had undifferentiated sarcoma, and 12 had other histology. Clinical TNM stage was stage I (41%), II (39%), III (6%), and IV (14%). First-line treatment was ifosfamide, vincristine, dactinomycin, whereas the second-line combination consisted of either cisplatin and doxorubicin (in MMT 84) or vincristine, carboplatin, etoposide/teniposide (in MMT 89). Chemotherapy doses were adapted to age. Local therapy was conservative surgery as often as possible. Results After a median follow-up of 7.8 years (range, 0.1 to 13 years), 5-year overall survival (OS) and event-free survival rates were 66% and 55% for the total study population and 72% and 60% for nonmetastatic patients, respectively. Only two of 13 stage IV patients survived. Sixty-seven percent of newborn infants survived. Infants with alveolar subtype had a poorer survival than those with non-RMS MMT or nonalveolar RMS (5-year OS, 37% v 75% or 82%, respectively; P = .002). When compared with older children with MMT, young age does not seem to be an important prognostic factor. Conclusion OS was satisfactory even when local treatment was not aggressive, although the prognosis was poor for infants with alveolar RMS or metastatic tumors. Chemotherapy toxicity was manageable with appropriate dose modification.

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Soft Tissue Sarcoma or Malignant Mesenchymal Tumors in the First Year of Life: Experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee

Yearbook of Oncology ◽

10.1016/s1040-1741(08)70476-7 ◽

2007 ◽

Vol 2007 ◽

pp. 290-291

Author(s):

R.J. Arceci

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

International Society ◽

Pediatric Oncology ◽

Life Experience ◽

Mesenchymal Tumor ◽

First Year ◽

Mesenchymal Tumors ◽

Malignant Mesenchymal Tumor ◽

First Year Of Life

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Randomized Comparison of Intensified Six-Drug Versus Standard Three-Drug Chemotherapy for High-Risk Nonmetastatic Rhabdomyosarcoma and Other Chemotherapy-Sensitive Childhood Soft Tissue Sarcomas: Long-Term Results From the International Society of Pediatric Oncology MMT95 Study

Journal of Clinical Oncology ◽

10.1200/jco.2011.40.3287 ◽

2012 ◽

Vol 30 (20) ◽

pp. 2457-2465 ◽

Cited By ~ 101

Author(s):

Odile Oberlin ◽

Annie Rey ◽

José Sanchez de Toledo ◽

Hélène Martelli ◽

Meriel E.M. Jenney ◽

...

Keyword(s):

High Risk ◽

Soft Tissue ◽

International Society ◽

Pediatric Oncology ◽

Local Therapy ◽

Survival Advantage ◽

Long Term Results ◽

Undifferentiated Sarcoma ◽

Response To Chemotherapy ◽

Significant Difference

Purpose MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial. Patients and Methods From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m2 (both arms), epirubicin 450 mg/m2, etoposide 1,350 mg/m2 (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other arm. Delivery of radiotherapy was determined according to site and/or response to chemotherapy with or without surgery. Results Overall survival (OS) for all patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in outcome in either OS or event-free survival was noted between the two arms (3-year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the six-drug arm). Toxicity was significantly greater (infection, myelosuppression, and mucositis) in the six-drug arm. Overall burden of local therapy was consistent with data from previous SIOP studies and showed no difference between the two chemotherapy regimens. Conclusion Intensification of chemotherapy for nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival advantage or reduction in the intensity of local therapy and adds toxicity.

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Treatment of Nonmetastatic Rhabdomyosarcoma in Childhood and Adolescence: Third Study of the International Society of Paediatric Oncology—SIOP Malignant Mesenchymal Tumor 89

Journal of Clinical Oncology ◽

10.1200/jco.2005.08.130 ◽

2005 ◽

Vol 23 (12) ◽

pp. 2618-2628 ◽

Cited By ~ 222

Author(s):

Michael C.G. Stevens ◽

Annie Rey ◽

Nathalie Bouvet ◽

Caroline Ellershaw ◽

Françoise Flamant ◽

...

Keyword(s):

Alkylating Agents ◽

Randomized Study ◽

Local Treatment ◽

Local Therapy ◽

Paediatric Oncology ◽

Mesenchymal Tumor ◽

Childhood And Adolescence ◽

Free Survival ◽

Malignant Mesenchymal Tumor ◽

Better Than

Purpose To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy. Patients and Methods Five hundred three previously untreated patients aged from birth to 18 years, recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage. Results Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy. Conclusion Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).

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Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.12.2177 ◽

1991 ◽

Vol 9 (12) ◽

pp. 2177-2182 ◽

Cited By ~ 73

Author(s):

A Suarez ◽

H McDowell ◽

P Niaudet ◽

E Comoy ◽

F Flamant

Keyword(s):

Renal Function ◽

International Society ◽

Pediatric Oncology ◽

Severe Toxicity ◽

Mesenchymal Tumors ◽

Primary Tumor Site ◽

Malignant Mesenchymal Tumor ◽

Long Term Follow Up ◽

Chemotherapy Protocol ◽

Beta 2

The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.

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