Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: A cohort study from the European paediatric Soft tissue sarcoma Study Group

Andrea Ferrari*, Daniel Orbach, Michela Casanova, Max M van Noesel, Pablo Berlanga, Bernadette Brennan, Nadege Corradini, Reineke A Schoot, Gema L Ramirez-Villar, Lisa Lyngsie Hjalgrim, Rita Alaggio, Gabriela Guillen Burrieza, Akmal Safwat, Alison L Cameron, Rick R van Rijn, Veronique Minard-Colin, Ilaria Zanetti, Gianni Bisogno, Julia C Chisholm, Johannes H M Merks

*Corresponding author for this work
6 Citations (Scopus)

Abstract

BACKGROUND: Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.

METHODS: This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.

RESULTS: The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2-111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6-25.7) and 34.9% (95% CI, 22.7-47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.

CONCLUSIONS: The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.

PLAIN LANGUAGE SUMMARY: Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors. Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases. This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.

Original languageEnglish
JournalCancer
Volume129
Issue number16
Pages (from-to)2542-2552
Number of pages11
ISSN0008-543X
DOIs
Publication statusPublished - 15 Aug 2023

Keywords

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols
  • Child
  • Cohort Studies
  • Humans
  • Neoplasm Recurrence, Local/drug therapy
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Rhabdomyosarcoma/drug therapy
  • Sarcoma/drug therapy
  • Soft Tissue Neoplasms/pathology
  • Young Adult
  • treatment
  • adolescents
  • prognostic factors
  • non-rhabdomyosarcoma soft tissue sarcomas
  • metastases
  • children
  • outcome

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