Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytoma
Alexandre Buffet
(1)
,
Laurene Ben Aim
(2)
,
Sophie Leboulleux
(3)
,
Delphine Drui
(4)
,
Delphine Vezzosi
(5)
,
Rossella Libé
(6)
,
Christiane Ajzenberg
(7)
,
Daniele Bernardeschi
(8)
,
Bertrand Cariou
(9)
,
Frédéric Chabolle
(10)
,
Olivier Chabre
(11)
,
Vincent Darrouzet
(12)
,
Brigitte Delemer
(13)
,
Rachel Desailloud
(14)
,
Bernard Goichot
(15)
,
Annabelle Esvant
(16)
,
Lucile Offredo
(17)
,
Philippe Herman
(18)
,
Sandrine Laboureau
,
Hervé Lefebvre
(19, 20)
,
Peggy Pierre
(21)
,
Isabelle Raingeard
(22)
,
Yves Reznik
(23)
,
Jean-Louis Sadoul
(24)
,
Julien Hadoux
(25)
,
Antoine Tabarin
(26)
,
Igor Tauveron
(27)
,
Delphine Zenaty
(28)
,
Judith Favier
(1)
,
Jérôme Bertherat
(6)
,
Éric Baudin
(29)
,
Laurence Amar
(1)
,
Anne-Paule Gimenez-Roqueplo
(1)
1
PARCC - UMR-S U970 -
Paris-Centre de Recherche Cardiovasculaire
2 HEGP - Hôpital Européen Georges Pompidou [APHP]
3 Médecine nucléaire
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 AMIENS - Endocrino - Service d'Endocrinologie
15 Service de Médecine Interne, Endocrinologie et Nutrition [CHU Strasbourg]
16 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital
17 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé
18 Hôpital Lariboisière
19 DC2N - Différenciation et communication neuronale et neuroendocrine
20 Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen]
21 TOURS - Endocrino - Service d'Endocrinologie
22 Service d'endocrinologie
23 Service Endocrinologie - Diabétologie [CHU Caen]
24 NICE - Endocrino - Service d'Endocrinologie
25 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
26 BORDEAUX - Endocrino - Service d'Endocrinologie
27 GReD - Génétique, Reproduction et Développement
28 Service de pédiatrie générale
29 IGR - Institut Gustave Roussy
2 HEGP - Hôpital Européen Georges Pompidou [APHP]
3 Médecine nucléaire
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 AMIENS - Endocrino - Service d'Endocrinologie
15 Service de Médecine Interne, Endocrinologie et Nutrition [CHU Strasbourg]
16 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital
17 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé
18 Hôpital Lariboisière
19 DC2N - Différenciation et communication neuronale et neuroendocrine
20 Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen]
21 TOURS - Endocrino - Service d'Endocrinologie
22 Service d'endocrinologie
23 Service Endocrinologie - Diabétologie [CHU Caen]
24 NICE - Endocrino - Service d'Endocrinologie
25 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
26 BORDEAUX - Endocrino - Service d'Endocrinologie
27 GReD - Génétique, Reproduction et Développement
28 Service de pédiatrie générale
29 IGR - Institut Gustave Roussy
Sophie Leboulleux
- Function : Author
- PersonId : 759169
- ORCID : 0000-0002-4824-8502
Daniele Bernardeschi
- Function : Author
- PersonId : 774007
- ORCID : 0000-0002-5937-8847
Bertrand Cariou
- Function : Author
- PersonId : 761594
- ORCID : 0000-0002-1580-8040
- IdRef : 075934981
Rachel Desailloud
- Function : Author
- PersonId : 767326
- ORCID : 0000-0001-9976-7938
- IdRef : 078643422
Sandrine Laboureau
- Function : Author
Hervé Lefebvre
- Function : Author
- PersonId : 180967
- IdHAL : herve-lefebvre
Laurence Amar
- Function : Author
- PersonId : 759846
- ORCID : 0000-0003-3942-4276
- IdRef : 092993508
Anne-Paule Gimenez-Roqueplo
- Function : Author
- PersonId : 764850
- ORCID : 0000-0002-4816-670X
- IdRef : 150517335
Abstract
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