Clinical Trial| Volume 60, P69-82, June 2016

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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

Published:April 12, 2016DOI:


      • This is the first prospective international study of extracranial MRT in children.
      • This study shows that intensive therapy can be delivered to a very young population of MRTs, with an improvement in outcome.
      • Age less than 1 year, metastatic disease and progression on treatment lead to a dismal outcome.
      • This evidence allows us to use this protocol as a standard chemotherapy backbone, for future studies with new agents.
      • It is unlikely we will improve the outcome with current chemotherapy which is already at maximal tolerance.



      Extracranial malignant rhabdoid tumours (MRT) are rare lethal childhood cancers that often occur in infants and have a characteristic genetic mutation in the SMARCB1 gene. The European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) conducted a multinational prospective study of registered cases of extracranial MRT to test an intensive multimodal approach of treatment for children with newly diagnosed extracranial MRT.


      Between December 2005 and June 2014, we prospectively registered 100 patients from 12 countries with a diagnosis of MRT tumour at an extracranial site on the EpSSG Non-Rhabdomyosarcoma Soft Tissue Sarcoma 2005 Study (NRSTS 2005). They were all treated on a standard multimodal protocol of surgery, radiotherapy, and chemotherapy over 30 weeks as follows: vincristine, cyclophosphamide, and doxorubicin (VDCy) at weeks 1, 10, 13, 22, and 28; vincristine was also given alone on weeks 2, 3, 11, 12, 14, 15, 23, 24, 29, and 30. Cyclophosphamide, carboplatin, and etoposide (Cy*CE) was given at weeks 4, 7, 16, 19, and 25. Radiotherapy was recommended for all primary tumour sites and all sites of metastatic disease.


      Forty-three patients completed the protocol treatment. Median follow-up for alive patients of the complete cohort was 44.6 months (range 11.5–84.6). For the whole cohort, the 3-year event-free survival (EFS) was 32.3% (95% confidence interval [CI] 23.2–41.6%) with a 3-year overall survival (OS) of 38.4% (95% CI 28.8–47.9%). For localised disease, the 4-year EFS was 39.3% (95% CI 28.2–50.1%) with a 4-year OS of 40.1% (95% CI 28.4–51.5%). For metastatic disease, the 2-year EFS was 8.7% (95% CI 1.5–24.2%) with a 2-year OS of 13.0% (95% CI 3.3–29.7%). Multivariable analysis disclosed that all patients ≤1 year of age were associated with at higher risk of death (hazard ratio [HR]: 2.6; 95% CI 1.0–6.8; p-value = 0.0094). Risk of death was also related with gender in metastatic patients (HR for males: 2.9, 95% CI 1.0–8.0; p-value = 0.0077).


      The EpSSG NRSTS 2005 protocol of intensive therapy can be delivered to extracranial MRT patients, with a possible improvement in outcome. The outcome, however, remains poor for patients who progress or with metastatic disease.


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