Prognosis of Malignant Pheochromocytoma and Paraganglioma (MAPP-Prono Study): A European Network for the Study of Adrenal Tumors Retrospective Study.


Journal

The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362

Informations de publication

Date de publication:
01 06 2019
Historique:
received: 11 09 2018
accepted: 29 01 2019
pubmed: 5 2 2019
medline: 28 4 2020
entrez: 5 2 2019
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 30715419
pii: 5304738
doi: 10.1210/jc.2018-01968
doi:

Substances chimiques

SDHB protein, human EC 1.3.5.1
Succinate Dehydrogenase EC 1.3.99.1

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

2367-2374

Informations de copyright

Copyright © 2019 Endocrine Society.

Auteurs

Segolene Hescot (S)

Department of Nuclear Medicine and Endocrine Tumors, Gustave Roussy, Villejuif, France.

Maria Curras-Freixes (M)

Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Timo Deutschbein (T)

Department of Internal Medicine and Central Laboratory, University Hospital of Würzburg, Würzburg, Germany.

Anouk van Berkel (A)

Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.

Delphine Vezzosi (D)

Department of Endocrinology, CHU Toulouse, Toulouse, France.

Laurence Amar (L)

Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France.
INSERM UMR970, Paris-Cardiovascular Research Center, Paris Descartes University, Paris, France.

Christelle de la Fouchardière (C)

Hospices Civils de Lyon and Centre Léon Bérard, University Lyon I, Lyon, France.

Nuria Valdes (N)

Department of Endocrinology and Nutrition, University Hospital Central de Asturias, Oviedo, Spain.
Unit of Endocrinology, Nutrition, Diabetes and Obesity, Institute of Sanitary Research of Asturias, Oviedo, Spain.

Fernando Riccardi (F)

Azienda Ospedaliera Antonio Cardarelli, Naples, Italy.

Christine Do Cao (C)

Department of Endocrinology, Hôpital Huriez, CHR-U, Lille, France.

Jerome Bertherat (J)

Department of Endocrinology, Hôpital Cochin, Paris, France.

Bernard Goichot (B)

Department of Internal Medicine, Endocrinology and Nutrition, University Hospital of Strasbourg, Strasbourg, France.

Felix Beuschlein (F)

Medical Clinics and Polyclinics IV, University Hospital of Munich, Munich, Germany.
Unit of Endocrinology, Nutrition, Diabetes, University Hospital of Zurich, Zurich, Switzerland.

Delphine Drui (D)

Department of Endocrinology, L'Institut du Thorax, CHU Nantes, Nantes, France.

Letizia Canu (L)

Department of Experimental and Clinical Biomedical Sciences, "Mario Serio," University of Florence, Florence, Italy.

Patricia Niccoli (P)

Department of Oncology, Institut Paoli Calmettes, Marseille, France.

Sandrine Laboureau (S)

Department of Endocrinology, CHU Angers, Angers, France.

Antoine Tabarin (A)

Department of Endocrinology, CHU Bordeaux, Bordeaux, France.

Sophie Leboulleux (S)

Department of Nuclear Medicine and Endocrine Tumors, Gustave Roussy, Villejuif, France.

Bruna Calsina (B)

Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Rossella Libé (R)

Department of Endocrinology, Hôpital Cochin, Paris, France.

Antongiulio Faggiano (A)

Division of Endocrinology, Department of Clinical Medicine and Surgery, Università Federico II, Naples, Italy.

Martin Schlumberger (M)

Department of Nuclear Medicine and Endocrine Tumors, Gustave Roussy, Villejuif, France.

Francoise Borson-Chazot (F)

Hospices Civils de Lyon and Centre Léon Bérard, University Lyon I, Lyon, France.

Massimo Mannelli (M)

Department of Experimental and Clinical Biomedical Sciences, "Mario Serio," University of Florence, Florence, Italy.

Anne-Paule Gimenez-Roqueplo (AP)

Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France.
INSERM UMR970, Paris-Cardiovascular Research Center, Paris Descartes University, Paris, France.

Philippe Caron (P)

Department of Endocrinology, CHU Toulouse, Toulouse, France.

Henri J L M Timmers (HJLM)

Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.

Martin Fassnacht (M)

Department of Internal Medicine and Central Laboratory, University Hospital of Würzburg, Würzburg, Germany.

Mercedes Robledo (M)

Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Isabelle Borget (I)

Department of Biostatistic and Epidemiology, Gustave Roussy, Villejuif, France.
University Paris-Saclay, University Paris-Sud, UVSQ, CESP ONCOSTAT, INSERM, Villejuif, France.

Eric Baudin (E)

Department of Nuclear Medicine and Endocrine Tumors, Gustave Roussy, Villejuif, France.

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Classifications MeSH