R Libé1, I Borget2, C L Ronchi3, B Zaggia4, M Kroiss5, T Kerkhofs6, J Bertherat7, M Volante8, M Quinkler9, O Chabre10, M Bala11, A Tabarin12, F Beuschlein13, D Vezzosi14, T Deutschbein11, F Borson-Chazot15, I Hermsen6, A Stell16, C Fottner17, S Leboulleux18, S Hahner11, M Mannelli19, A Berruti20, H Haak6, M Terzolo4, M Fassnacht11, E Baudin21. 1. French Adrenal Cancer Network, Institut National du Cancer, Paris. 2. Department of Biostatistics and Epidemiology, Gustave Roussy and University Paris-Sud, Villejuif, France. 3. Central Laboratory, Research Unit, University Hospital Wurzburg, Wurzburg, Germany. 4. Internal Medicine, San Luigi Hospital, University of Turin, Italy. 5. Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany. 6. Internal Medicine, Maxima Medisch Centrum, Eindhoven, The Netherlands. 7. Endocrinology Unit, Cochin Hospital, Paris, France. 8. Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy. 9. Clinical Endocrinology, Charit Campus Mitte, Charitί University Medicine Berlin, Germany. 10. Endocrinology Unit, University Hospital of Grenoble, France. 11. Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany. 12. Department of Endocrinology, CHU Bordeaux, University of Bordeaux, Bordeaux, France. 13. Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany. 14. Department of Endocrinology and Metabolic Diseases, CHU Larrey, Toulouse. 15. Nuclear Medicine Unit, University of Lyon 1, Hospices Civils de Lyon Bron, France. 16. Melbourne eResearch Group Level 3, Doug McDonell Building, University of Melbourne, Melbourne, Australia. 17. Department of Medicine 1, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. 18. Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave Roussy, Villejuif, France. 19. Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', Florence. 20. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Spedali Civili Hospital, Brescia, Italy. 21. Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave Roussy, Villejuif, France eric.baudin@gustaveroussy.fr.
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. PATIENTS AND 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. CONCLUSION: The mENSAT classification and GRAS parameters (Grade, R status, Age and Symptoms) were found to best stratify the prognosis of patients with advanced ACC.
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. PATIENTS AND 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. CONCLUSION: The mENSAT classification and GRAS parameters (Grade, R status, Age and Symptoms) were found to best stratify the prognosis of patients with advanced ACC.
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