title: Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?
abstract: BACKGROUND
  SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population.
  
  
  METHODS
  Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis.
  
  
  RESULTS
  Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis.
  
  
  CONCLUSIONS
  The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.
authors.affiliation: Unit of Paediatric Haematology and Oncology, Department of Clinical and Experimental Medicine, Hospital Policlinico, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.
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authors.affiliation: Department "GF Ingrassia", University of Catania, Via Santa Sofia 87, 95123, Catania, Italy.
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authors.lastname: Agodi
authors.affiliation: Unidad de Oncologia Pediatrica, Hospital Universitari i Politecnic La Fe, Avenida Fernando Abril Martorell, 106, 46026, Valencia, Spain. julbagui@yahoo.es.
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authors.affiliation: Department "GF Ingrassia", University of Catania, Via Santa Sofia 87, 95123, Catania, Italy.
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authors.affiliation: Unidad de Oncologia Pediatrica, Hospital Universitari i Politecnic La Fe, Avenida Fernando Abril Martorell, 106, 46026, Valencia, Spain.
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authors.affiliation: Unidad de Oncologia Pediatrica, Hospital Universitari i Politecnic La Fe, Avenida Fernando Abril Martorell, 106, 46026, Valencia, Spain.
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mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein
keywords: Eligibility; Infant; Metastatic; Neuroblastoma; Survival