Maxime Enault1, Véronique Minard-Colin2, Nadège Corradini3, Guy Leverger4, Estelle Thebaud5, Angélique Rome6, Stéphanie Proust7, Aude Marie-Cardine8, Anne-Sophie Defachelles9, Sabine Sarnacki10, Pascale Philippe-Chomette11, Olivier Delattre12, Julien Masliah-Planchon13, Brigitte Lacour14, Andrea Ferrari15, Bernadette Brennan16, Daniel Orbach17, Franck Bourdeaut18. 1. Assistance Publique-Hôpitaux de Paris, Pediatric Emergency Department, Armand Trousseau University Hospital, Sorbonne Université, Paris, France; SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris, France. 2. Department of Children and Adolescents Oncology, Gustave Roussy Cancer Center, Villejuif, France. 3. Pediatric Oncology Department, Institute of Pediatric Hematology and Oncology, Centre Leon Berard, Lyon, France. 4. Department of Pediatric Onco-Hematology, Armand Trousseau University Hospital, Paris, France. 5. Department of Pediatric Oncology, Mother and Child Hospital, Nantes, France. 6. Department of Pediatric Onco-Hematology, Hôpital D'Enfants La Timone, Marseille, France. 7. Pediatric Oncology Department, University Hospital, Angers, France. 8. Pediatric Hemato-Oncology Department, University Hospital, Rouen, France. 9. Department of Pediatric Oncology, Oscar Lambret Cancer Center, Lille, France. 10. Department of Pediatric Surgery, Necker Enfants-Malades University Hospital, Université de Paris, France. 11. Department of Pediatric Surgery, Robert Debré University Hospital, Paris, France. 12. SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris, France; INSERM U830, Diversity and Plasticity of Tumors, Paris, France. 13. Department of Diagnostic and Theranostic Molecular Pathology, Unit of Somatic Genetic, Institut Curie, Paris, France. 14. Registre National des Cancers de L'Enfant, Registre National des Tumeurs Solides de l'Enfant, CHRU Nancy, France. 15. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. 16. Pediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK. 17. SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris, France. 18. SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris, France; INSERM U830, Laboratory of Translationnal Research in Pediatric Oncology, Paris, France. Electronic address: franck.bourdeaut@curie.fr.
Abstract
BACKGROUND AND AIMS: Extracranial malignant rhabdoid tumours are tumours that mainly affect young children and have a poor prognosis. In 2014, the European Paediatric Soft-tissue sarcoma Study Group developed treatment recommendations consisting in intensive dose chemotherapy every 2 weeks using vincristine-doxorubicin-cyclophosphamide (VDCy) and ifosfamide-etoposide (IE) associated with early surgery and irradiation of tumour sites. METHODS: A retrospective study was conducted on children treated in France by these new recommendations up to January 2019. RESULTS: Thirty-five patients were identified. The primary tumour was in miscellaneous soft parts for 18 patients, in the kidney for 11 and in the liver for six. The median age at diagnosis was 17.5 months (range 1.2-198.2). Distant locations (metastatic or synchronous tumours) were present in 37.1% at diagnosis. SMARCB1 germline pathogenic variant was detected in 17.1% of patients. Overall tolerance was good, with 87-97% of theoretical chemotherapy cumulative doses actually delivered. The median interval between two courses was 18 days. Surgical resection was performed in 83% (19 R0, 7 R1 and 3 R2) and local radiotherapy in 49% of patients. After a median follow-up of 50.4 months (range 16.5-134.1), the 2-year overall and event-free survivals were 47.6% (95% confidence interval [CI] 30.2-63.1) and 42.9% (95% [CI] 26.5-58.3), respectively. On univariate analyses, localised disease and gross total resection were significantly associated with favourable outcomes. CONCLUSIONS: Intensive dose chemotherapy with VDCy/IE can be administrated with no remarkable short-term toxicity, including in infants. However, the outcome remains poor for patients without gross total resection and with metastatic or multifocal disease. These patients could be stratified into a high-risk group that requires a new immediate therapeutic approach such as targeted agents combined with multimodal therapy.
BACKGROUND AND AIMS: Extracranial malignant rhabdoid tumours are tumours that mainly affect young children and have a poor prognosis. In 2014, the European Paediatric Soft-tissue sarcoma Study Group developed treatment recommendations consisting in intensive dose chemotherapy every 2 weeks using vincristine-doxorubicin-cyclophosphamide (VDCy) and ifosfamide-etoposide (IE) associated with early surgery and irradiation of tumour sites. METHODS: A retrospective study was conducted on children treated in France by these new recommendations up to January 2019. RESULTS: Thirty-five patients were identified. The primary tumour was in miscellaneous soft parts for 18 patients, in the kidney for 11 and in the liver for six. The median age at diagnosis was 17.5 months (range 1.2-198.2). Distant locations (metastatic or synchronous tumours) were present in 37.1% at diagnosis. SMARCB1 germline pathogenic variant was detected in 17.1% of patients. Overall tolerance was good, with 87-97% of theoretical chemotherapy cumulative doses actually delivered. The median interval between two courses was 18 days. Surgical resection was performed in 83% (19 R0, 7 R1 and 3 R2) and local radiotherapy in 49% of patients. After a median follow-up of 50.4 months (range 16.5-134.1), the 2-year overall and event-free survivals were 47.6% (95% confidence interval [CI] 30.2-63.1) and 42.9% (95% [CI] 26.5-58.3), respectively. On univariate analyses, localised disease and gross total resection were significantly associated with favourable outcomes. CONCLUSIONS: Intensive dose chemotherapy with VDCy/IE can be administrated with no remarkable short-term toxicity, including in infants. However, the outcome remains poor for patients without gross total resection and with metastatic or multifocal disease. These patients could be stratified into a high-risk group that requires a new immediate therapeutic approach such as targeted agents combined with multimodal therapy.
Authors: Andrea Ferrari; Bernadette Brennan; Michela Casanova; Nadege Corradini; Pablo Berlanga; Reineke A Schoot; Gema L Ramirez-Villar; Akmal Safwat; Gabriela Guillen Burrieza; Patrizia Dall'Igna; Rita Alaggio; Lisa Lyngsie Hjalgrim; Susanne Andrea Gatz; Daniel Orbach; Max M van Noesel Journal: Cancer Manag Res Date: 2022-09-23 Impact factor: 3.602