Highlights
- •Developing research for non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is challenging.
- •Recent tailored studies by cooperative groups have defined a standard of care for NRSTS.
- •A multimodal risk-adapted treatment approach is mandatory for patients with NRSTS.
- •International prospective dedicated programs with adults are needed.
Abstract
The current article focuses on non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), the
heterogeneous group of mesenchymal tumours different from rhabdomyosarcoma that may
affect children and adolescents, with clinical behaviour varying from relatively benign
to highly malignant. This review represents the effort of the international scientific
paediatric community within the context of the INternational Soft Tissue SaRcoma ConsorTium
(INSTRuCT), a project founded by the leadership of three large cooperative groups
– Children's Oncology Group, Cooperative Weichteilsarkom Studiengruppe and European
paediatric Soft tissue sarcoma Study Group – with the main goal to pool expertise
and resources on a broader international level in order to improve knowledge of soft
tissue sarcomas of children, adolescents and young adults.
This article describes the current standard treatment approach in NRSTS, with a focus
on the controversies and challenges in the management of these tumours. Developing
research projects and clinical protocols for NRSTS has always been challenging, supporting
the need to develop international integrated prospective dedicated programs, including
paediatric NRSTS experts together with the adult sarcoma community. INSTRuCT provides
a unique mechanism to increase international collaboration by agreeing on a common
language, developing consensus standards to guide diagnosis and treatment, comparing
clinical trial results across cooperative groups, and through a shared data dictionary
providing answers to questions that can only be addressed by a larger data set.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Soft tissue sarcoma across the age spectrum: a population-based study from the Surveillance Epidemiology and End Results database.Pediatr Blood Cancer. 2011; 57: 943-949
- Epidemiology and survivorship of soft tissue sarcomas in adults: a national cancer database report.Cancer Med. 2014; 3: 1404-1415
- Defining and listing very rare cancers of pediatric age: consensus of the joint action on rare cancers (JARC) in cooperation with the European cooperative study group for pediatric rare tumors (EXPeRT).Eur J Cancer. 2019; 110: 120-126
- Soft tissue and bone tumours.5th ed. WHO classification of tumours series. vol. 3. International Agency for Research on Cancer, Lyon (France)2020 (ISBN 978-92-832-4502-5)
- A summary of the inaugural WHO Classification of Pediatric Tumors: transitioning from the optical into the molecular era.Cancer Discov. 2022; (in press)https://doi.org/10.1158/2159-8290.CD-21-1094
- Rhabdomyosarcoma.Nat Rev Dis Prim. 2019; 5: 1
- Soft tissue sarcomas in adolescents and young adults: a comparison with their paediatric and adult counterparts.Lancet Oncol. 2017; 18: e166-e175
- The challenge of the management of adolescents and young adults with soft tissue sarcomas.Pediatr Blood Cancer. 2018; 65e27013
- Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome.J Clin Oncol. 2003; 21: 1602-1611
- Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution.Cancer. 2004; 101: 627-634
- Synovial sarcoma of children and adolescents: the prognostic role of axial sites.Eur J Cancer. 2008; 44: 1202-1209
- Synovial sarcoma in childhood and adolescence: a retrospective series of 77 patients registered by the Children's Cancer and Leukaemia Group between 1991 and 2006.Pediatr Blood Cancer. 2010; 55: 85-90
- Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group.Pediatr Blood Cancer. 2011; 57: 1130-1136
- Int-Veen C, et al. Grossly-resected synovial sarcoma treated by the German and Italian pediatric soft tissue sarcoma cooperative group: discussion on the role of adjuvant therapies.Pediatr Blood Cancer. 2006; 46: 11-17
- Int-Veen C, Harms D, et al. Cooperative trial CWS-91 for localized soft tissue sarcoma in children, adolescents, and young adults.J Clin Oncol. 2009 Mar 20; 27: 1446-1455
- The effect of adjuvant therapies on long-term outcome for primary resected synovial sarcoma in a series of mainly children and adolescents.J Cancer Res Clin Oncol. 2021 Dec; 147: 3735-3747
- Synovial sarcoma in children and adolescents: the European pediatric soft tissue sarcoma study group prospective trial (EpSSG NRSTS 2005).Ann Oncol. 2015; 26: 567-572
- Surgery alone is sufficient therapy for children and adolescents with low-risk synovial sarcoma: a joint analysis from the European paediatric Soft tissue sarcoma Study Group and the Children's Oncology Group.Eur J Cancer. 2017; 78: 1-6
- Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital.J Clin Oncol. 1999; 17: 3697e705
- Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma.J Clin Oncol. 2002; 20: 3225e35
- Adult-type soft tissue sarcomas in pediatric-age patients: experience at the Istituto Nazionale Tumori in Milan.J Clin Oncol. 2005; 23: 4021-4030
- Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study.Med Pediatr Oncol. 1998; 30: 201-209
- Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study.J Clin Oncol. 1999; 17: 1219
- Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience.Med Pediatr Oncol. 1999; 33: 76-82
- Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study.J Clin Oncol. 2005; 23: 4031-4038
- Adult-type soft tissue sarcomas in pediatric age: a nomogram-based prognostic comparison with adult sarcomas.Eur J Cancer. 2007; 43: 2691e7
- A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study.Lancet Oncol. 2020 Jan; 21: 145-161
- Pediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European pediatric Soft tissue sarcoma Study Group (EpSSG).Lancet Child Adolesc Health. 2021 Aug; 5: 546-558
- Postoperative nomogram for 12-year sarcoma-specific death.J Clin Oncol. 2002; 20: 791-796
- Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis.Lancet Oncol. 2016; 17: 671-680
- Grading of nonrhabdomyosarcoma soft tissue sarcoma in children and adolescents: a comparison of parameters used for the Federation Nationale des Centers de Lutte Contre le Cancer and Pediatric Oncology Group Systems.Cancer. 2010; 116: 2266-2274
- Adjuvant chemotherapy for adult soft tissue sarcomas of extremities and girdles: results of the Italian randomized cooperative trial.J Clin Oncol. 2001; 19: 1238-1247
- Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.J Clin Oncol. 2012; 30: 850-856
- Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: final results of a randomized trial from Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups.J Clin Oncol. 2020; 38: 2178-2186
- Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data.Lancet. 1997; 350: 1647-1654
- A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma.Cancer. 2008; 113: 573-581
- The role of adjuvant chemotherapy in children and adolescents with surgically-resected high-risk adult-type soft tissue sarcomas.Pediatr Blood Cancer. 2005; 45: 128-134
- Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: radiation Therapy Oncology Group Trial 9514.J Clin Oncol. 2006; 24: 619-625
- The impact of chemotherapy on survival of patients with extremity and trunk wall soft tissue sarcoma: revisiting the results of the EORTC-STBSG 62931 randomised trial.Eur J Cancer. 2019; 109: 51-60
- Outcomes of metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated within the BERNIE study: a randomised, phase II study evaluating the addition of bevacizumab to chemotherapy.Eur J Cancer. 2020 May; 130: 72-80
- Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European cooperative groups.J Clin Oncol. 2008 May 10; 26: 2384-2389
- Non-metastatic unresected pediatric nonrhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups.Eur J Cancer. 2011; 47: 724e31
- Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials.Eur J Cancer. 2019 May; 112: 98-106
- Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial.Lancet Oncol. 2020 Aug; 21: 1110-1122
- The effects of pazopanib on doxorubicin pharmacokinetics in children and adults with non-rhabdomyosarcoma soft tissue sarcoma: a report from Children's Oncology Group and NRG Oncology study ARST1321.Cancer Chemother Pharmacol, 2022 Jan 27https://doi.org/10.1007/s00280-022-04397-4 (Epub ahead of print. PMID: 35083502)
- Identified enrollment challenges of adolescent and young adult patients on the nonchemotherapy arm of Children's oncology group study ARST1321.J Adolesc Young Adult Oncol. 2021 Sep 9; (Epub ahead of print. PMID: 34515544)https://doi.org/10.1089/jayao.2021.0103
- Introducing INSTRuCT: an international effort to promote cooperation and data sharing.Pediatr Blood Cancer. 2020 Sep 12; ([Online ahead of print])e28701https://doi.org/10.1002/pbc.28701
- Controversies and challenges in the management of pediatric non-rhabdomyosarcoma soft tissue sarcomas.Lancet Child Adolesc Health. 2022; (in press)https://doi.org/10.1016/S2352-4642(22)00036-0
- Should soft tissue sarcomas be treated at high-volume centers? An analysis of 4205 patients.Ann Surg. 2007; 245: 952-958
- Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the european CONnective TIssue CAncer NETwork (CONTICANET).Ann Oncol. 2013; 24: 1685-1691
- Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study.Ann Oncol. 2014; 25: 225-231
- Management of sarcomas in children, adolescents and adults: interactions in two different age groups under the umbrellas of GSF-GETO and SFCE, with the support of the NETSARC+ network.Bull Cancer. 2021 Feb; 108: 163-176
- Locally aggressive rarely metastazing tumors and low-grade sarcoma in children, adolescents and young adults: the benefits of a national network.Eur J Surg Oncol. 2021 Sep 14; (7983(21)00732-0) ([Online ahead of print]): S0748https://doi.org/10.1016/j.ejso.2021.09.006
- Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions.Ann Oncol. 2012 Sep; 23: 2442-2449
- Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas.J Clin Oncol. 2013; 31: 608-615
- Response to chemotherapy is not related to chromosome instability in synovial sarcoma.Ann Oncol. 2014; 25: 2267-2271
- Genomic complexity in pediatric synovial sarcoma (SYNOBIO study): the European pediatric soft tissue sarcoma group (EpSSG NRSTS 2005) experience.Cancer Med. 2018; 7: 1384-1393
- Non-rhabdomyosarcoma soft-tissue sarcoma.Pediatr Blood Cancer. 2021 May; 68e28279
- The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy.Ann Surg. 1982; 196: 305-315
- Preoperative intensity modulated radiation therapy compared to three-dimensional conformal radiation therapy for high-grade extremity sarcomas in children: analysis of the Children's Oncology Group Study ARST0332.Int J Radiat Oncol Biol Phys. 2019; 103: 38-44
- Quality assurance in radiation oncology.Pediatr Blood Cancer. 2021 May; 68e28609https://doi.org/10.1002/pbc.28609
- Alveolar soft part sarcoma in children and adolescents: the European Paediatric Soft Tissue Sarcoma study group prospective trial (EpSSG NRSTS 2005).Pediatr Blood Cancer. 2018; 65
- Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect.Ann Oncol. 2011; 22: 1682-1690
- Cediranib for metastatic alveolar soft part sarcoma.J Clin Oncol. 2013; 31: 2296-2302
- Long-term results of treatment of advanced dermatofibrosarcoma protuberans (DFSP) with imatinib mesylate - the impact of fibrosarcomatous transformation.Eur J Surg Oncol. 2017; 43: 1134-1141
- Dermatofibrosarcoma protuberans in children and adolescents: the European paediatric soft tissue sarcoma study group prospective trial (EpSSG NRSTS 2005).Pediatr Blood Cancer. 2020 Oct; 67e28351
- Dermatofibrosarcoma protuberans in children and adolescents: primary and relapsed disease-experience of the cooperative weichteilsarkomstudiengruppe (CWS).J Surg Oncol. 2020 Aug; 122: 263-272
- Complete cytoreduction and HIPEC improves survival in desmoplastic small round cell tumor.Ann Surg Oncol. 2014; 21: 220-224
- Multi-agent chemotherapy including IrIVA regimen and maintenance therapy in the treatment of desmoplastic small round cell tumor.Tumori. 2021 Feb 17; ([Online ahead of print])300891621995250https://doi.org/10.1177/0300891621995250
- Outcome of extracranial malignant rhabdoid tumours in children registered in the European paediatric soft tissue sarcoma study group non-rhabdomyosarcoma soft tissue sarcoma 2005 study-EpSSG NRSTS 2005.Eur J Cancer. 2016; 60: 69-82
- Extracranial rhabdoid tumours: results of a SFCE series of patients treated with a dose compression strategy according to European Paediatric Soft tissue sarcoma Study Group recommendations.Eur J Cancer. 2022 Jan; 161: 64-78https://doi.org/10.1016/j.ejca.2021.10.025
- Extraosseous Ewing sarcoma in children and adolescents: a retrospective series from a referral pediatric oncology center.Pediatr Blood Cancer. 2021 Dec 28; ([Online ahead of print])e29512https://doi.org/10.1002/pbc.29512
- Extraskeletal Ewing sarcoma in children, adolescents, and young adults. An analysis of three prospective studies of the Cooperative Weichteilsarkomstudiengruppe (CWS).Pediatr Blood Cancer. 2021 Oct; 68e29145
- Desmoid tumors in children: the experience of the European pediatric Soft tissue sarcoma Study Group (EpSSG) – NRSTS 05 study – an international prospective case series.Lancet Child & Adolescent Health. 2017; 1: 284-292
- Systemic therapy of aggressive fibromatosis in children and adolescents: report of the Cooperative Weichteilsarkom Studiengruppe (CWS).Pediatr Blood Cancer. 2018 May; 65e26943
- Inflammatory myofibroblastic tumors-A retrospective analysis of the Cooperative Weichteilsarkom Studiengruppe.Pediatr Blood Cancer. 2018 Jun; 65e27012
- Inflammatory myofibroblastic tumor: the experience of the European paediatric soft tissue sarcoma study group (EpSSG).Eur J Cancer. 2020 Mar; 127: 123-129
- Conservative strategy in infantile fibrosarcoma is possible: the European pediatric Soft tissue sarcoma Study Group experience.Eur J Cancer. 2016; 57: 1-9
- The impact of local control in the treatment of children with advanced infantile and adult-type fibrosarcoma: experience of the cooperative weichteilsarkom studiengruppe (CWS).J Pediatr Surg. 2020 Sep; 55: 1740-1747
- Spotlight on the treatment of infantile fibrosarcoma in the era of neurotrophic tropomyosin receptor kinase inhibitors: international consensus and remaining controversies.Eur J Cancer. 2020 Sep; 137: 183-192
- Sarcoma classification by DNA methylation profiling.Nat Commun. 2021 Jan 21; 12: 498
- The new horizon of liquid biopsy in sarcoma: the potential utility of circulating tumor nucleic acids.J Cancer. 2020 Jul 9; 11: 5293-5308
- Sarcoma spheroids and organoids-promising tools in the era of personalized medicine.Int J Mol Sci. 2018 Feb 21; 19: 615
- The pediatric precision oncology INFORM Registry: clinical outcome and benefit for patients with very high-evidence targets.Cancer Discov. 2021 Nov; 11: 2764-2779
- Current state of pediatric sarcoma biology and opportunities for future discovery: a report from the sarcoma translational research workshop.Cancer Genet. 2016 May; 209: 182-194
Article info
Publication history
Published online: April 28, 2022
Accepted:
March 18,
2022
Received in revised form:
March 9,
2022
Received:
February 4,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.