Journal Article

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

Darrouzet, Vincent, Esvant, Annabelle, Chabre, Olivier, Buffet, Alexandre, Pierre, Peggy, Laboureau, Sandrine, Tauveron, Igor, Offredo, Lucile, Herman, Philippe, Lefebvre, Hervé, Zenaty, Delphine, Amar, Laurence, Libé, Rossella, Hadoux, Julien, Tabarin, Antoine, Cariou, Bertrand, Favier, Judith, Delemer, Brigitte, Vezzosi, Delphine, Chabolle, Frédéric, Bertherat, Jérôme, Reznik, Yves, Drui, Delphine, Sadoul, Jean-Louis, Baudin, Eric, Leboulleux, Sophie, Gimenez-Roqueplo, Anne-Paule, Desailloud, Rachel, Ajzenberg, Christiane, Goichot, Bernard, Bernardeschi, Daniele, Raingeard, Isabelle, Ben Aim, Laurène

2019

Overview

Abstract 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. Knowledge of the germline SDHx or VHL mutation status at the time of PPGL diagnosis is associated with a closer follow-up and an earlier tumor diagnosis.

• Publisher: Endocrine Society,Copyright Oxford University Press,Oxford University Press
• Subject: Adolescent / Adrenal Gland Neoplasms - diagnosis / Adrenal Gland Neoplasms - genetics / Adrenal Gland Neoplasms - mortality / Adult / Aftercare - methods / Aftercare - statistics & numerical data / Aged / Cellular Biology / Child / Diagnosis / Disease susceptibility / Endocrinology and metabolism / Female / Follow-Up Studies / Gene mutations / Genetic screening / Genetic Testing / Germ-Line Mutation / Human health and pathology / Humans / Kaplan-Meier Estimate / Life Sciences / Lost to Follow-Up / Male / Medical screening / Metastases / Metastasis / Middle Aged / Mutation / Neoplasms, Multiple Primary - diagnosis / Neoplasms, Multiple Primary - genetics / Neoplasms, Multiple Primary - mortality / Neuroendocrine tumors / Paraganglioma / Paraganglioma - diagnosis / Paraganglioma - genetics / Paraganglioma - mortality / Patient outcomes / Pheochromocytoma / Pheochromocytoma - diagnosis / Pheochromocytoma - genetics / Pheochromocytoma - mortality / Prognosis / Retrospective Studies / Succinate Dehydrogenase - genetics / Survival Rate / Tissues and Organs / VHL protein / Von Hippel-Lindau Tumor Suppressor Protein - genetics / Young Adult