Paediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG).

Autor:	Ferrari A; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. Electronic address: andrea.ferrari@istitutotumori.mi.it., van Noesel MM; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Division Cancer and Imaging, University Medical Center Utrecht, Utrecht, Netherlands., Brennan B; Paediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK., Zanetti I; Hematology Oncology Division, Department of Women's and Children's Health, University of Padova, Padova, Italy., Corradini N; Department of Pediatric Oncology, Institut d'Hematologie et d'Oncologie Pédiatrique/Centre Léon Bérard, Lyon, France., Casanova M; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy., Berlanga P; Department of Pediatric and Adolescent Oncology, Gustave-Roussy, Cancer Campus, Université Paris-Saclay, Villejuif, France., Merks JHM; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands., Alaggio R; Pathology Department, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy., Schifflers S; Department of Pediatrics, Clinique CHC MontLégia, Liège, Belgium., Ramirez-Villar GL; Pediatric Oncology Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain., Giraudo C; Department of Medicine DIMED, University of Padova, Padova, Italy., Burrieza GG; Surgical Oncology and Neonatal Surgery, Pediatric Surgery Department, Hospital Infantil Universitari Vall d'Hebron, Barcelona, Spain., Safwat A; Oncology Department and Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark., Bisogno G; Hematology Oncology Division, Department of Women's and Children's Health, University of Padova, Padova, Italy., De Salvo GL; Clinical Research Unit, IRCCS Istituto Oncologico Veneto, Padova, Italy., Orbach D; SIREDO Oncology Center, Institut Curie, PSL University, Paris, France.
Jazyk:	angličtina
Zdroj:	The Lancet. Child & adolescent health [Lancet Child Adolesc Health] 2021 Aug; Vol. 5 (8), pp. 546-558. Date of Electronic Publication: 2021 Jun 30.
DOI:	10.1016/S2352-4642(21)00159-0
Abstrakt:	Background: A standardised approach to treatment of paediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS), which account for about 4% of childhood cancers, is still lacking. We report the results of the NRSTS 2005 protocol developed specifically by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) to determine a risk-adapted multimodal standard of care for this group of tumours. Methods: The EpSSG NRSTS 2005 study included two prospective, non-randomised, historically controlled trials (one on localised adult-type NRSTS and the other on localised synovial sarcoma) done at 100 academic centres and hospitals in 14 countries. Patients younger than 21 years with a pathologically proven diagnosis of synovial sarcoma or an adult-type NRSTS, no evidence of metastatic disease, no previous treatment other than primary surgery, and diagnostic specimens available for pathological review were included. Patients were stratified by surgical stage, tumour size, nodal involvement, tumour grade (for adult-type NRSTS), and tumour site (for synovial sarcoma). Patients were then divided into four treatment groups: surgery alone, adjuvant radiotherapy, adjuvant chemotherapy (with or without radiotherapy), or neoadjuvant chemotherapy (with or without radiotherapy). The main chemotherapy regimen was ifosfamide (3·0 g/m 2 intravenously per day for 3 days) plus doxorubicin (37·5 mg/m 2 intravenously per day for 2 days); only ifosfamide (3·0 g/m 2 intravenously per day for 2 days) was given concomitantly with radiotherapy (delivered with three-dimensional conformal external beam technique, using conventional fractionation [1·8 daily fractions, 5 days per week] at a dose of 50·4 Gy or 54·0 Gy, to a maximum of 59·4 Gy). The number of chemotherapy cycles ranged from three to seven depending on the stage of the disease. The primary outcomes were event-free survival and overall survival. This study has been completed, and is registered under EudraCT, 2005-001139-31. Findings: Between May 31, 2005, and Dec 31, 2016, 1321 patients were enrolled, of whom 569 (206 with synovial sarcoma and 363 with adult-type NRSTS), with a median age of 12·6 years (IQR 8·2-14·9), were included in this analysis. With a median follow-up of 80·0 months (IQR 54·3-111·3) for the 467 patients alive, 5-year event-free survival was 73·7% (95% CI 69·7-77·2) and 5-year overall survival was 83·8% (95% CI 80·3-86·7). 5-year event-free survival was 91·4% (95% CI 87·0-94·4) and 5-year overall survival was 98·1% (95% CI 95·0-99·3) in the surgery alone group (n=250); 75·5% (46·9-90·1) and 88·2% (60·6-96·9) in the adjuvant radiotherapy group (n=17); 65·6% (54·8-74·5) and 75·8% (65·3-83·5) in the adjuvant chemotherapy group (n=93); and 56·4% (49·3-63·0) and 70·4% (63·3-76·4) in the neoadjuvant chemotherapy group (n=209). Reported severe adverse events included one case of generalised seizures (probably related to ifosfamide) and six cases of secondary tumours. Interpretation: Findings from the EpSSG NRSTS 2005 study help to define the risk-adapted standard of care for this patient population. Adjuvant treatment can be safely omitted in the low-risk population (classified here as the surgery alone group). Improving the outcome for patients with high-risk, initially resected adult-type NRSTS and those with initially unresectable disease remains a major clinical challenge. Funding: Fondazione Città della Speranza. Competing Interests: Declaration of interests We declare no competing interests. (Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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