Highlights
- •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.
Abstract
Background
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.
Methods
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.
Results
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).
Conclusions
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.
Keywords
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Article info
Publication history
Published online: April 12, 2016
Accepted:
February 23,
2016
Received in revised form:
December 22,
2015
Received:
October 23,
2015
Identification
Copyright
© 2016 Elsevier Ltd. All rights reserved.
