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

Ferrari A, Orbach D, Casanova D, van Noesel MM, Berlanga P, Brennan B, Corradini N, Schoot RA, Ramirez-Villar GA, Hjalgrim LL, Alaggio R, Guillen Burrieza G, Safwat A, Cameron A, van Rijn RR, Minard-Colin V, Zanetti I, Bisogno G, Chisholm J, Merks JHM. Cancer 2023 Apr 21. doi: 10.1002/cncr.34814. Online ahead of print

Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors. While 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 at onset.

This study reports on 61 patients <21 years old with adult-type metastatic NRSTS enrolled from July 2008 to December 2016 in two concurrent prospective EpSSG studies, i.e. the randomized BERNIE study and the single-arm MTS 2008 study. 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 twelve cycles of maintenance therapy, while radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had

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% 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.

The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge. Together with the subgroup of 80 metastatic patients enrolled in the COG ARST0332 study, this series may represent the reference for this disease category, and serve as the starting point for developing future dedicated investigational trials.