TY - JOUR
T1 - 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
AU - Brennan, Bernadette
AU - De Salvo, Gian Luca
AU - Orbach, Daniel
AU - De Paoli, Angela
AU - Kelsey, Anna
AU - Mudry, Peter
AU - Francotte, Nadine
AU - Van Noesel, Max
AU - Bisogno, Gianni
AU - Casanova, Michela
AU - Ferrari, Andrea
N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Chemoradiotherapy, Adjuvant
KW - Child
KW - Child, Preschool
KW - Cyclophosphamide/administration & dosage
KW - Disease-Free Survival
KW - Doxorubicin/administration & dosage
KW - Female
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Male
KW - Neoplasm Staging
KW - Prospective Studies
KW - Rhabdoid Tumor/mortality
KW - Sarcoma/mortality
KW - Vincristine/administration & dosage
UR - https://www.scopus.com/pages/publications/84963546042
U2 - 10.1016/j.ejca.2016.02.027
DO - 10.1016/j.ejca.2016.02.027
M3 - Article
C2 - 27082136
SN - 1879-0852
VL - 60
SP - 69
EP - 82
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -