Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma

Alexandre Buffet (1) , Laurène Ben Aim (2) , Sophie Leboulleux (3) , Delphine Drui (4) , Delphine Vezzosi (5) , Rossella Libé (6) , Christiane Ajzenberg (7) , Daniele Bernardeschi (8) , Bertrand Cariou (4) , Frédéric Chabolle (9) , Olivier Chabre (10) , Vincent Darrouzet (11) , Brigitte Delemer (12) , Rachel Desailloud (13) , Bernard Goichot (14) , Annabelle Esvant (15) , Lucile Offredo (1) , Philippe Herman (16) , Sandrine Laboureau (17) , Hervé Lefebvre (18, 19) , Peggy Pierre (20) , Isabelle Raingeard (21) , Yves Reznik (22) , Jean-Louis Sadoul (23) , Julien Hadoux (24) , Antoine Tabarin (25) , Igor Tauveron (26) , Delphine Zenaty (27) , Judith Favier (1) , Jérôme Bertherat (6) , Eric Baudin (24) , Laurence Amar (28, 2) , Anne-Paule Gimenez-Roqueplo (1, 2, 28)

1 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
2 HEGP - Hôpital Européen Georges Pompidou [APHP]
3 Médecine nucléaire
4 CHU Nantes - Centre hospitalier universitaire de Nantes
5 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
6 Hôpital Cochin [AP-HP]
7 Hôpital Henri Mondor
8 CHU Pitié-Salpêtrière [AP-HP]
9 Hôpital Foch [Suresnes]
10 CHU - Centre Hospitalier Universitaire [Grenoble]
11 CHU de Bordeaux Pellegrin [Bordeaux]
12 CHU Reims - Centre Hospitalier Universitaire de Reims
13 CHU Amiens-Picardie
14 Les Hôpitaux Universitaires de Strasbourg (HUS)
15 CHU Pontchaillou [Rennes]
16 Hôpital Lariboisière-Fernand-Widal [APHP]
17 CHU Angers - Centre Hospitalier Universitaire d'Angers
18 DC2N - Différenciation et communication neuronale et neuroendocrine
19 CHU Rouen
20 CHU Trousseau [Tours]
21 CHU - Hôpital Lapeyronie [Montpellier]
22 CHU Caen
23 CHU - Hôpital Archet 2 [Nice]
24 Université Paris-Saclay
25 CHU Bordeaux [Bordeaux]
26 CHU Clermont-Ferrand
27 AP-HP Hôpital universitaire Robert-Debré [Paris]
28 UPCité UFR Pharmacie - Université Paris Cité - UFR Pharmacie [Santé]

Context : Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL. Objective : Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL. Design : We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. 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 : Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127). Conclusion : Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.

Domains: Life Sciences [q-bio]; Human health and pathology; Endocrinology and metabolism; Life Sciences [q-bio]; Cellular Biology; Life Sciences [q-bio]; Human health and pathology; Tissues and Organs [q-bio.TO]

Alexandre Buffet, Laurène Ben Aim, Sophie Leboulleux, Delphine Drui, Delphine Vezzosi, et al.. Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma. Journal of Clinical Endocrinology and Metabolism, 2019, 104 (4), pp.1109-1118. ⟨10.1210/jc.2018-02411⟩. ⟨hal-02419895⟩