NRSTS 2005 study

The term non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) collectively includes a heterogeneous group of neoplasms of presumed mesenchymal origin, different from rhabdomyosarcoma, that occur in childhood and adolescence and may vary in clinical course from relatively benign to highly malignant.

The overall cure rate for NRSTS patients, in fact, is around 70%, but survival is known to depend to the presence of the different prognostic variables such histotype and grade of malignancy, disease extension at onset (e.g. presence of metastases, tumor size), tumor site.

In 2005, the EpSSG designed a comprehensive protocol – EpSSG NRSTS 2005 - that included two prospective non-randomized studies, for patients <21 years old with localised synovial sarcoma and localised so called adult-type NRSTS, and specific clinical recommendations for the other NRSTS histotypes. The EpSSG NRSTS 2005 study was conducted from 2005 to 2016 and involved 100 academic centres and hospitals in 14 different countries (Argentina, Belgium, Czech Republic, Denmark, France, Ireland, Israel, Italy, the Netherlands, Norway, Slovakia, Slovenia, Spain, and the UK).

The EpSSG has reported the analyses of various specific histological subgroups (those requiring a specific treatment approach) as well as the treatment results of the whole series of patients enrolled in the prospective non-randomized part of the protocol.
Patients were stratified by surgical stage, tumour size, nodal involvement, tumour grade, and tumour site, and were treated according to a multidisciplinary approach that required ifosfamide-doxorubicin chemotherapy as adjuvant treatment in resected high-risk NRSTS (tumors that are larger than 5 cm and high grade) and neoadjuvant treatment in advanced disease.

The main achievement of the EpSSG NRSTS 2005 study was that, together with the results of the COG ARST0332 study, it represents the current benchmark for NRSTS and define the risk-adapted standard of care.
Concerning the main part of the study (on adult-type NRSTS, including synovial sarcoma), 569 patients were involved and 5-year EFS and OS were 73.7% and 83.8%, respectively. The study demonstrated: that adjuvant treatment can be safely omitted in the low-risk population; that although prognosis for grossly resected NRSTS was generally good, patients with high-grade and large tumours are at high risk of metastatic spread; and that neoadjuvant ifosfamide plus doxorubicin chemotherapy improved resectability rate and survival in patients with initially unresected cases, compared with previous studies.
Concerning specific histotypes, two main results of the EpSSG NRSS 2005 study are: an initial wait-and-see strategy could be considered a correct approach in desmoid-type fibromatosis since it did not compromise outcomes and reduced treatment burden; a conservative therapy (with alkylating/anthracycline free chemotherapy) is possible in most patients with infantile fibrosarcoma

Coordinating Investigator NRSTS2005

Andrea Ferrari
Pediatric Oncology Unit, Istituto Nazionale Tumori,
Milano, Italy

Ferrari AndreaItalyPediatric Oncology Unit, Istituto Nazionale Tumori, Milano
Van Noesel MaxNetherlandsConsultant Pediatric Oncologist, Princess Maxima Center, Utrecht
Corradini NadegeFranceInstitute of Pediatric Hematology and Oncology (IHOPe), Department of Leon Berard Center
Schoot ReinekeNetherlandsPrincess Maxima Hospital, Utrecht
Berlanga PabloFranceGustave Roussy, Paris
Ramirez-Villar GemaSpainHospital Universitario Virgen del Rocío, Sevilla
Orbach DanielFranceInstitute Curie, Centre Integre de soins e de rechercheen oncologie de l'enfant, adolescent e jeune adulte, Paris
Casanova MichelaItalyPediatric Oncology Unit, Istituto Nazionale Tumori, Milano