MyKids: Molecular Identification and Characterization of non-Rhabdomyosarcoma Soft Tissue Sarcoma in Kids, Adolescents and Young Adults: an EpSSG NRSTS study

Pediatric NRSTS are a relatively rare (incidence is 4-6/100.000, 2-4% of all
pediatric tumors) and heterogeneous group of soft tissue sarcomas. It includes
many histologic types and subtypes with a significant degree of overlap in
morphology and immunoprofile. Diagnosis is traditionally based on histology,
immunohistochemistry, and genetic alterations. One of the main problems is
inconclusive diagnosis, resulting in *undifferentiated* or *unclassified*
sarcoma. In addition, there is a considerable lack of knowledge of the tumor
driver events in (pediatric) sarcoma. The previous EpSSG-NRSTS-2005 study
evaluated the role of standard treatment (including chemotherapy) in pediatric
NRSTS in Europe. This revealed that the prognosis in children is generally
similar or more favorable than in adults. Unfavorable groups included
*unclassified sarcomas* to a high degree.

Molecular alterations, especially chromosomal translocations are common in STS
and result in highly specific chimeric genes characteristic for a certain
histiotype. Detection of specific recurring genetic alterations has reduced the
number of *undifferentiated/unclassified* diagnoses, albeit that entities still
remain unclassified. In addition, an estimated 10% of histological diagnoses
are altered after molecular analysis of tumor material that elucidates a
diagnostic translocation. In addition, novel transcripts are being detected and
increase the knowledge and diagnostic potential in STS. Lastly, in an
increasing number of STS, detected genetic alterations determine treatment
options.

The MYKIDS study is designed to better understand the potential for molecular
diagnosis of pediatric NRSTS with a view to optimize treatment. In particular,
to a) understand the value of molecular profiling in pediatric NRSTS, b) enable
a comprehensive decision on the treatment options for individual patients, c)
compare molecular profiles to histological grading for prognostication, d)
build tumor models to identify and test new treatments, e) identify cell free
tumor DNA and circulating tumor cells and assessing responses to treatment in a
non-invasive manner (liquid biopsies), and f) to collect post-treatment tissue
to characterize molecular progression markers.

The MyKids study is a biological study towards the molecular profiling of
pediatric NRSTS, the development of NRSTS tumoroid cultures, the establishment
of liquid biopsy biomarkers and the molecular profiling of post-treatment
tissue samples. The overall aim is to better understand the potential for
molecular diagnosis of pediatric NRSTS with a view to optimize treatment.

International, multicenter, prospective study

This study is a NRSTS biological study for molecular profiling, embedded in the
multi-national framework of the EpSSG to allow the collection of samples from
all over Europe and countries outside the EU of localized and disseminated
NRSTS. This study is divided into five work packages (WPs). Participation in
the entire study requires at least participation in WP2

The risks of study participation are negligible, as biopsy and molecular
profiling of tumor material will be performed as part of standard of care. For
interpretation of sequencing results, comparison with germline sequencing is
needed, for which an extra tube of blood is needed, to be collected in
combination with regular blood withdrawals. This is also a standard of care
procedure.

The only additional material collected for study purposes are the blood samples
for the detection of circulating tumor DNA (liquid biopsies). These blood
withdrawals will be combined with standard of care blood withdrawals as much as
possible. Treatment interventions are not part of this study protocol, but data
will be captured as part of the registry.