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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.

Publication ,  Journal Article
Hettmer, S; Linardic, CM; Kelsey, A; Rudzinski, ER; Vokuhl, C; Selfe, J; Ruhen, O; Shern, JF; Khan, J; Kovach, AR; Lupo, PJ; Gatz, SA ...
Published in: Eur J Cancer
September 2022

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.

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Published In

Eur J Cancer

DOI

EISSN

1879-0852

Publication Date

September 2022

Volume

172

Start / End Page

367 / 386

Location

England

Related Subject Headings

  • Soft Tissue Neoplasms
  • Risk Assessment
  • Rhabdomyosarcoma, Embryonal
  • Rhabdomyosarcoma
  • Prospective Studies
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Molecular Diagnostic Techniques
  • Humans
  • Consensus
 

Citation

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Chicago
ICMJE
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Hettmer, S., Linardic, C. M., Kelsey, A., Rudzinski, E. R., Vokuhl, C., Selfe, J., … Shipley, J. (2022). 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. Eur J Cancer, 172, 367–386. https://doi.org/10.1016/j.ejca.2022.05.036
Hettmer, Simone, Corinne M. Linardic, Anna Kelsey, Erin R. Rudzinski, Christian Vokuhl, Joanna Selfe, Olivia Ruhen, et al. “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.Eur J Cancer 172 (September 2022): 367–86. https://doi.org/10.1016/j.ejca.2022.05.036.
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. 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. Eur J Cancer. 2022 Sep;172:367–386.
Journal cover image

Published In

Eur J Cancer

DOI

EISSN

1879-0852

Publication Date

September 2022

Volume

172

Start / End Page

367 / 386

Location

England

Related Subject Headings

  • Soft Tissue Neoplasms
  • Risk Assessment
  • Rhabdomyosarcoma, Embryonal
  • Rhabdomyosarcoma
  • Prospective Studies
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Molecular Diagnostic Techniques
  • Humans
  • Consensus