Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Standard of Care and Treatment Recommendations from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)

Abstract

This paper describes the standard of care for patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) and the therapeutic recommendations developed by the European paediatric Soft tissue sarcoma Study Group (EpSSG). NRSTS form a very mixed group of mesenchymal extraskeletal malignancies. Their rarity, heterogeneity, and aggressiveness make the management of children and adolescents with these tumors complex and challenging. The overall cure rate for patients with NRSTS is around 70%, but survival depends on several prognostic variables, such as histotype and tumor grade, extent of disease and stage, tumor size, and tumor site. While surgery remains the mainstay of treatment for most of these tumors, a multimodal therapeutic approach including radiotherapy and chemotherapy is required in many cases. The EpSSG NRSTS 2005 study was the first prospective protocol tailored specifically to NRSTS. Together with the ARST0332 study developed by the North-American Soft Tissue Sarcoma Committee of the Children’s Oncology Group (COG), the EpSSG NRSTS 2005 study currently represents the benchmark for these tumors, establishing risk-adapted standards of care. The EpSSG has developed common treatment recommendations for the large group of adult-type NRSTS (including synovial sarcoma), and specific treatment recommendations for other particular adult-type histologies (ie, alveolar soft-part sarcoma, clear cell sarcoma and dermatofibrosarcoma protuberans); other highly malignant tumors with a biology and clinical behavior differing from those of adult-type NRSTS (ie, rhabdoid tumors and desmoplastic small round cell tumor); and soft tissue tumors of intermediate malignancy (ie desmoid-type fibromatosis, inflammatory myofibroblastic tumors, and infantile fibrosarcoma). New effective drugs are needed for patients whose NRSTS carries the worst prognosis, ie, those with unresectable tumors, metastases at diagnosis, or relapsing disease. Progress in this area relies on our ability to develop international integrated prospective collaborations, both within existing pediatric oncology networks and, importantly, between the communities of specialists treating pediatric and adult sarcoma.

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols

“…There was a nonsignificant trend toward higher EFS and OS and a lower risk of tumor spillage in patients operated after neoadjuvant chemotherapy. This result is similar to the results published by the SIOP group for Wilms’ tumor and hepatoblastoma compared to the North American approach of upfront surgical resection 10,11 . Similarly, the ARST00332 study focusing on NRSTS identified the risk of increased marginal resection rate with upfront compared to delayed resections, although without impact on survival 9 .…”

“…This result is similar to the results published by the SIOP group for Wilms' tumor and hepatoblastoma compared to the North American approach of upfront surgical resection. 10,11 Similarly, the ARST00332 study focusing on NRSTS identified the risk of increased marginal resection rate with upfront compared to delayed resections, although without impact on survival. 9 The effects of primary versus delayed resection were not assessed in the North American study on UESL.…”

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma: comparison of long-term outcome between radiotherapy and chemotherapy

“…However, there were studies showing no improvement in outcomes associating with the use of chemotherapy [28] . In principle, adult-type NRSTS are usually assumed to be relatively insensitive to chemotherapy, with reported tumor response in the range of 40%-50%, or even less, and RT has a role in local control after incomplete resections and even after wide excisions in the case of large tumors [29] . Thus, our study further provides the evidence of RT and chemotherapy in the treatment of NRSTS, revealing RT is more appropriate for orbital NRSTS.…”

Intra-Abdominal Desmoplastic Small Round Cell Tumor (DSRCT) and the Role of Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Review

“…The additional value of HIPEC, regardless of regimen, remains unclear, and in view of the associated toxicity of HIPEC without a proven survival benefit, its use should be restricted to a very selected patient population and preferably within a study context.. The combination of induction chemotherapy, surgery, and WART has been included in the latest ‘Standard of Care and Treatment Recommendations’ for pediatric non-rhabdomyosarcoma soft tissue sarcoma from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) [ 62 ].…”