title: Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study.
abstract: BACKGROUND
  The clinical course of advanced adrenocortical carcinoma (ACC) is heterogeneous. Our study aimed primarily to refine and make headway in the prognostic stratification of advanced ACC.
  
  
  METHODS
  Patients with advanced ENSAT ACC (stage III or stage IV) at diagnosis registered between 2000 and 2009 in the ENSAT database were enrolled. The primary end point was overall survival (OS). Parameters of potential prognostic relevance were selected. Univariate and multivariate analyses were carried out: model 1 'before surgery'; model 2 'post-surgery'.
  
  
  RESULTS
  Four hundred and forty-four patients with advanced ENSAT ACC (stage III: 210; stage IV: 234) were analyzed. After a median follow-up of 55.2 months, the median OS was 24 months. A modified ENSAT (mENSAT) classification was validated: stage III (invasion of surrounding tissues/organs or the vena renalis/cava) and stage IVa, IVb, IVc (2, 3 or >3 metastatic organs, including N, respectively). Two- or 5-year OS was 73%, 46%, 26% and 15% or 50%, 15%, 14% and 2% for stages III, IVa, IVb and IVc, respectively. In the multivariate analysis, mENSAT stages (stages IVa, IVb, or IVc, respectively) were significantly correlated with OS (P < 0.0001), as well as additional parameters: age ≥ 50 years (P < 0.0001), tumor- or hormone-related symptoms (P = 0.01 and 0.03, respectively) in model 1 but also the R status (P = 0.001) and Grade (Weiss >6 and/or Ki67 ≥ 20%, P = 0.06) in model 2.
  
  
  CONCLUSIONS
  The mENSAT classification and GRAS parameters (Grade, R status, Age and Symptoms) were found to best stratify the prognosis of patients with advanced ACC.
authors.affiliation: French Adrenal Cancer Network, Institut National du Cancer, Paris.
authors.forename: R
authors.initials: R
authors.lastname: Libé
authors.affiliation: Department of Biostatistics and Epidemiology, Gustave Roussy and University Paris-Sud, Villejuif, France.
authors.forename: I
authors.initials: I
authors.lastname: Borget
authors.affiliation: Central Laboratory, Research Unit, University Hospital Wurzburg, Wurzburg, Germany.
authors.forename: C L
authors.initials: CL
authors.lastname: Ronchi
authors.affiliation: Internal Medicine, San Luigi Hospital, University of Turin, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Zaggia
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kroiss
authors.affiliation: Internal Medicine, Maxima Medisch Centrum, Eindhoven, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Kerkhofs
authors.affiliation: Endocrinology Unit, Cochin Hospital, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Bertherat
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Volante
authors.affiliation: Clinical Endocrinology, Charit Campus Mitte, Charitί University Medicine Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Quinkler
authors.affiliation: Endocrinology Unit, University Hospital of Grenoble, France.
authors.forename: O
authors.initials: O
authors.lastname: Chabre
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bala
authors.affiliation: Department of Endocrinology, CHU Bordeaux, University of Bordeaux, Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Tabarin
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Beuschlein
authors.affiliation: Department of Endocrinology and Metabolic Diseases, CHU Larrey, Toulouse.
authors.forename: D
authors.initials: D
authors.lastname: Vezzosi
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Deutschbein
authors.affiliation: Nuclear Medicine Unit, University of Lyon 1, Hospices Civils de Lyon Bron, France.
authors.forename: F
authors.initials: F
authors.lastname: Borson-Chazot
authors.affiliation: Internal Medicine, Maxima Medisch Centrum, Eindhoven, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Hermsen
authors.affiliation: Melbourne eResearch Group Level 3, Doug McDonell Building, University of Melbourne, Melbourne, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Stell
authors.affiliation: Department of Medicine 1, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Fottner
authors.affiliation: Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave Roussy, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Leboulleux
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hahner
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', Florence.
authors.forename: M
authors.initials: M
authors.lastname: Mannelli
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Spedali Civili Hospital, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Internal Medicine, Maxima Medisch Centrum, Eindhoven, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Haak
authors.affiliation: Internal Medicine, San Luigi Hospital, University of Turin, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Terzolo
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Fassnacht
authors.affiliation: Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave Roussy, Villejuif, France eric.baudin@gustaveroussy.fr.
authors.forename: E
authors.initials: E
authors.lastname: Baudin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000401:mortality / Q000473:pathology*; D018268:Adrenocortical Carcinoma / Q000401:mortality / Q000473:pathology*; D001859:Bone Neoplasms / Q000401:mortality / Q000556:secondary*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
keywords: ENSAT; GRAS; adrenocortical carcinoma; prognostic factors