Segolene Hescot1, Maria Curras-Freixes2, Timo Deutschbein3, Anouk van Berkel4, Delphine Vezzosi5, Laurence Amar6,7, Christelle de la Fouchardière8, Nuria Valdes9,10, Fernando Riccardi11, Christine Do Cao12, Jerome Bertherat13, Bernard Goichot14, Felix Beuschlein15,16, Delphine Drui17, Letizia Canu18, Patricia Niccoli19, Sandrine Laboureau20, Antoine Tabarin21, Sophie Leboulleux1, Bruna Calsina2, Rossella Libé13, Antongiulio Faggiano22, Martin Schlumberger1, Francoise Borson-Chazot8, Massimo Mannelli18, Anne-Paule Gimenez-Roqueplo6,7, Philippe Caron5, Henri J L M Timmers4, Martin Fassnacht3, Mercedes Robledo2, Isabelle Borget23,24, Eric Baudin1. 1. Department of Nuclear Medicine and Endocrine Tumors, Gustave Roussy, Villejuif, France. 2. Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. 3. Department of Internal Medicine and Central Laboratory, University Hospital of Würzburg, Würzburg, Germany. 4. Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. 5. Department of Endocrinology, CHU Toulouse, Toulouse, France. 6. Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France. 7. INSERM UMR970, Paris-Cardiovascular Research Center, Paris Descartes University, Paris, France. 8. Hospices Civils de Lyon and Centre Léon Bérard, University Lyon I, Lyon, France. 9. Department of Endocrinology and Nutrition, University Hospital Central de Asturias, Oviedo, Spain. 10. Unit of Endocrinology, Nutrition, Diabetes and Obesity, Institute of Sanitary Research of Asturias, Oviedo, Spain. 11. Azienda Ospedaliera Antonio Cardarelli, Naples, Italy. 12. Department of Endocrinology, Hôpital Huriez, CHR-U, Lille, France. 13. Department of Endocrinology, Hôpital Cochin, Paris, France. 14. Department of Internal Medicine, Endocrinology and Nutrition, University Hospital of Strasbourg, Strasbourg, France. 15. Medical Clinics and Polyclinics IV, University Hospital of Munich, Munich, Germany. 16. Unit of Endocrinology, Nutrition, Diabetes, University Hospital of Zurich, Zurich, Switzerland. 17. Department of Endocrinology, L'Institut du Thorax, CHU Nantes, Nantes, France. 18. Department of Experimental and Clinical Biomedical Sciences, "Mario Serio," University of Florence, Florence, Italy. 19. Department of Oncology, Institut Paoli Calmettes, Marseille, France. 20. Department of Endocrinology, CHU Angers, Angers, France. 21. Department of Endocrinology, CHU Bordeaux, Bordeaux, France. 22. Division of Endocrinology, Department of Clinical Medicine and Surgery, Università Federico II, Naples, Italy. 23. Department of Biostatistic and Epidemiology, Gustave Roussy, Villejuif, France. 24. University Paris-Saclay, University Paris-Sud, UVSQ, CESP ONCOSTAT, INSERM, Villejuif, France.
Abstract
BACKGROUND: Malignant pheochromocytoma and paraganglioma (MPP) are characterized by prognostic heterogeneity. Our objective was to look for prognostic parameters of overall survival (OS) in MPP patients. PATIENTS AND METHODS: Retrospective multicenter study of MPP characterized by a neck-thoraco-abdomino-pelvic CT or MRI at the time of malignancy diagnosis in European centers between 1998 and 2010. RESULTS: One hundred sixty-nine patients from 18 European centers were included. Main characteristics of patients with MPP were: primary pheochromocytoma in 53% of patients; tumor- or hormone-related symptoms in 57% or 58% of cases; positive plasma or urine hormones in 81% of patients; identification of a mutation in SDHB in 42% of cases. Metastatic sites included bone (64%), lymph node (40%), lung (29%), and liver (26%); mean time between initial and malignancy diagnosis was 43 months (range, 0 to 614). Median follow-up was 68 months and median survival 6.7 years. Using univariate analysis, better survival was associated with head and neck paraganglioma, age <40 years, metanephrines less than fivefold the upper limits of the normal range, and low proliferative index. In multivariate analysis, hypersecretion [hazard ratio 3.02 (1.65 to 5.55); P = 0.0004] was identified as an independent significant prognostic factor of worst OS. CONCLUSIONS: Our results do not confirm SDHB mutations as a major prognostic parameter in MPP and suggest additional key molecular events involved in MPP tumor progression. Aside from SDHB mutation, the biology of aggressive MPP remains to be understood.
BACKGROUND:Malignant pheochromocytoma and paraganglioma (MPP) are characterized by prognostic heterogeneity. Our objective was to look for prognostic parameters of overall survival (OS) in MPP patients. PATIENTS AND METHODS: Retrospective multicenter study of MPP characterized by a neck-thoraco-abdomino-pelvic CT or MRI at the time of malignancy diagnosis in European centers between 1998 and 2010. RESULTS: One hundred sixty-nine patients from 18 European centers were included. Main characteristics of patients with MPP were: primary pheochromocytoma in 53% of patients; tumor- or hormone-related symptoms in 57% or 58% of cases; positive plasma or urine hormones in 81% of patients; identification of a mutation in SDHB in 42% of cases. Metastatic sites included bone (64%), lymph node (40%), lung (29%), and liver (26%); mean time between initial and malignancy diagnosis was 43 months (range, 0 to 614). Median follow-up was 68 months and median survival 6.7 years. Using univariate analysis, better survival was associated with head and neck paraganglioma, age <40 years, metanephrines less than fivefold the upper limits of the normal range, and low proliferative index. In multivariate analysis, hypersecretion [hazard ratio 3.02 (1.65 to 5.55); P = 0.0004] was identified as an independent significant prognostic factor of worst OS. CONCLUSIONS: Our results do not confirm SDHB mutations as a major prognostic parameter in MPP and suggest additional key molecular events involved in MPP tumor progression. Aside from SDHB mutation, the biology of aggressive MPP remains to be understood.
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