title: Outcome and prognostic factors in high-risk childhood adrenocortical carcinomas: A report from the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT).
abstract: The aim of this retrospective international analysis was to evaluate the role of risk factors in pediatric patients with adrenocortical carcinoma (ACC) observed in European countries (2000-2013) in an attempt to identify factors associated with poor prognosis.
  
  
  
  Data were retrieved from databases of Germany, France, Poland, and Italy, which form the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT). Patients were less than 18 years old, with at least one of the following tumor-related risk factors: metastases, volume more than 200 cm3, Cushing syndrome, vascular or regional lymph node invasion, initial biopsy, or incomplete excision. Role of patients' age was also evaluated.
  
  
  
  Eighty-two patients were evaluated: 62 with localized disease and 20 with metastases. The 3-year progression-free survival (PFS) and overall survival (OS) were 39% and 55% for the whole population, respectively, and 51% and 73% for localized diseases, respectively. Concerning the whole population, PFS and OS were influenced by distant metastases, tumor volume, lymph node involvement, age, and presence of two or more risk factors. Factors significant only at OS were vascular involvement and incomplete surgery. At multivariable analysis, the main factors at PFS were volume more than 200 cm3(hazard ratio [HR]: 2.6, 95% confidence interval [CI]: 1.18-5.70) and presence of distant metastases (HR: 8.26, 95% CI: 3.49-19.51). The OS was significantly influenced by the presence of metastases (P < 0.0001). Concerning patients with localized tumors, the only significant prognostic factor was volume more than 200 cm3with a HR of 4.38 (95% CI: 1.60-12.00) for PFS and of 3.68 (95% CI: 1.02-13.30) for OS.
  
  
  
  Distant metastases and large tumor volume were the main unfavorable prognostic factors. Presence of two or more factors related to ACC was associated with an aggressive behavior of disease.
authors.affiliation: Pediatric Surgery Unit, Department of Woman's and Children's Health, University Hospital of Padua, Padua, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cecchetto
authors.affiliation: Pediatric Surgery Unit, Department of Woman's and Children's Health, University Hospital of Padua, Padua, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Ganarin
authors.affiliation: Department of Pediatrics, Medical University, Gdansk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Bien
authors.affiliation: Pediatric Oncology Department, Otto von Guericke University Children's Hospital, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Vorwerk
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Woman's and Children's Health, University Hospital of Padua, Padua, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bisogno
authors.affiliation: Department of Pediatric Surgery, Marciniak Hospital, Wroclaw, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Godzinski
authors.affiliation: Pediatric Surgery Unit, Department of Woman's and Children's Health, University Hospital of Padua, Padua, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dall'Igna
authors.affiliation: Oncology and Hematology Unit, French Pediatric Rare Tumor Group (groupe Fracture), CHU de Saint Denis de La Réunion., Saint Denis, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Reguerre
authors.affiliation: Clinic of Pediatrics, Municipal Hospital Dortmund, Dortmund, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schneider
authors.affiliation: Pediatric Department, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.affiliation: Pediatric Department, Centre Oscar Lambret, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Leblond
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: University Children's Hospital, Erlangen, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Brecht
authors.affiliation: Clinical Trials and Biostatistics Unit, IRCCS Istituto Oncologico Veneto, Padua, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Department of Pediatric, Adolescent, Young Adult Oncology, French Pediatric Rare Tumor group (groupe Fracture), Institut Curie, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D012307:Risk Factors; D015996:Survival Rate
keywords: adolescents; adrenocortical carcinoma; children; risk factors