Molecular testing of rhabdomyosarcoma in clinical trials to improve risk stratification and outcome: A consensus view from European paediatric Soft tissue sarcoma Study Group, Children's Oncology Group and Cooperative Weichteilsarkom-Studiengruppe.
Date
2022-09-01Author
Hettmer, S
Linardic, CM
Kelsey, A
Rudzinski, ER
Vokuhl, C
Selfe, J
Ruhen, O
Shern, JF
Khan, J
Kovach, AR
Lupo, PJ
Gatz, SA
Schäfer, BW
Volchenboum, S
Minard-Colin, V
Koscielniak, E
Hawkins, DS
Bisogno, G
Sparber-Sauer, M
Venkatramani, R
Merks, JHM
Shipley, J
Type
Journal Article
Metadata
Show full item recordAbstract
Rhabdomyosarcomas (RMSs) are the most common soft tissue sarcomas in children/adolescents less than 18 years of age with an annual incidence of 1-2/million. Inter/intra-tumour heterogeneity raise challenges in clinical, pathological and biological research studies. Risk stratification in European and North American clinical trials previously relied on clinico-pathological features, but now, incorporates PAX3/7-FOXO1-fusion gene status in the place of alveolar histology. International working groups propose a coordinated approach through the INternational Soft Tissue SaRcoma ConsorTium to evaluate the specific genetic abnormalities and generate and integrate molecular and clinical data related to patients with RMS across different trial settings. We review relevant data and present a consensus view on what molecular features should be assessed. In particular, we recommend the assessment of the MYOD1-LR122R mutation for risk escalation, as it has been associated with poor outcomes in spindle/sclerosing RMS and rare RMS with classic embryonal histopathology. The prospective analyses of rare fusion genes beyond PAX3/7-FOXO1 will generate new data linked to outcomes and assessment of TP53 mutations and CDK4 amplification may confirm their prognostic value. Pathogenic/likely pathogenic germline variants in TP53 and other cancer predisposition genes should also be assessed. DNA/RNA profiling of tumours at diagnosis/relapse and serial analyses of plasma samples is recommended where possible to validate potential molecular biomarkers, identify new biomarkers and assess how liquid biopsy analyses can have the greatest benefit. Together with the development of new molecularly-derived therapeutic strategies that we review, a synchronised international approach is expected to enhance progress towards improved treatment assignment, management and outcomes for patients with RMS.
Collections
Subject
Rhabdomyosarcoma
adolescent
gene signatures
germ line and somatic genetics
molecular biomarkers
molecular targets
paediatric
young adults
Adolescent
Child
Consensus
Humans
Molecular Diagnostic Techniques
Neoplasm Recurrence, Local
Prospective Studies
Rhabdomyosarcoma
Rhabdomyosarcoma, Embryonal
Risk Assessment
Soft Tissue Neoplasms
Research team
Sarcoma Mol Pathol
Language
eng
Date accepted
2022-05-22
License start date
2022-09-01
Citation
European Journal of Cancer, 2022, 172 pp. 367 - 386
Publisher
ELSEVIER SCI LTD