Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytoma
2 HEGP - Hôpital Européen Georges Pompidou [APHP]
3 Médecine nucléaire [Gustave Roussy]
4 Service d'Endocrinologie [Nantes]
5 Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse]
6 Hôpital Cochin [AP-HP]
7 Hôpital Henri Mondor
8 CISIC - Centre d'Information sur la Surdité et l'Implant Cochléaire [Paris]
9 ITX - ITX - unité de recherche de l'institut du thorax
10 Service d'oto-rhino-laryngologie
11 Service d'endocrinologie
12 CHU de Bordeaux Pellegrin [Bordeaux]
13 Service d'Endocrinologie - Diabète - Nutrition [Reims]
14 Endocrinologie, Maladies métaboliques et Nutrition [CHU Amiens]
15 Service de Médecine Interne, Endocrinologie et Nutrition [CHU Strasbourg]
16 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
17 Hôpital Lariboisière
18 DC2N - Différenciation et communication neuronale et neuroendocrine
19 Service d'Endocrinologie, Diabétologie et Maladies Métaboliques [CHU Rouen]
20 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
21 Service d'endocrinologie
22 Service Endocrinologie - Diabétologie [CHU Caen]
23 Service d'endocrinologie [CHU Nice]
24 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
25 BORDEAUX - Endocrino - Service d'Endocrinologie
26 GReD - Génétique, Reproduction et Développement
27 Service de pédiatrie générale
28 IGR - Institut Gustave Roussy
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Résumé
OC5.1 Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytoma Context Paragangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumors, characterized by a strong genetic component. Indeed, up to 40% of patients carry a germline mutation in a PPGL susceptibility gene. In accordance with the international recommendations, genotyping of PPGL susceptibility genes is therefore proposed to all patients with PPGL, but it has actually never been shown whether the identification of a germline mutation in one PPGL susceptibility gene changes the outcome of mutation-carriers. Objective Our objective was to evaluate how a positive genetic test impacts the management and outcome of propositus patients with PPGL carrying a germline mutation in one of the four major PPGL susceptibility genes (SDHB, SDHD, SDHC and VHL). Design We performed a multicentric retrospective study on 221 propositus carrying a SDHB, SDHD, SDHC or VHL germline mutation and followed in 24 French clinical centers of the Group of Endocrine Tumors and/or the COMETE network. Patients were divided into two groups: Genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and Historic patients who only benefited from the genetic test several years after initial PPGL diagnosis. Results Compared to Historic patients, Genetic patients had a better follow-up, with a higher number of examinations and a reduced number of patients lost to follow-up (9.6% versus 72%). During follow-up, smaller (18.7 mm versus 27.6, PZ0.0128) new PPGL and metastases as well as lower metastatic spread were observed in Genetic patients. Importantly, these differences were reversed in the Historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival than Historic ones (PZ0.0127). Conclusion Altogether our study clearly shows the positive impact of the identification of an SDHx or VHL mutation in the management, clinical outcome and survival of patients with PPGL. It reveals, for the first time, the clinical benefits of the practice of oncogenetics for patients with a rare cancer and strongly strengthens the recommendations of the Endocrine Society to consider PPGL genetic testing in all patients affected by PPGL. DOI: 10.1530/endoabs.63.OC5.1
