Adults with paraganglioma or pheochromocytoma who received genetic testing early after diagnosis were more likely to receive better follow-up care and experience a less severe disease course vs. similar patients who underwent genetic testing years later, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
Since 2000, the identification of SDHD, SDHC and SDHB germline mutations in paragangliomas and pheochromocytomas has improved understanding of the genetic determinism of rare neuroendocrine tumors, which have an estimated prevalence of 1 in 10,000, Anne-Paule Gimenez-Roqueplo, MD, PhD, professor in the department of genetics at Assistance Publique-Hôpitaux de Paris and at Paris Descartes University, and colleagues wrote in the study background. Researchers now know that up to 40% of patients with a paraganglioma and pheochromocytoma carry a germline mutation in one of the 17 susceptibility genes reported so far, including three proto-oncogenes and 14 tumor suppressor genes.
“Paraganglioma and pheochromocytoma are the endocrine tumors the most impacted by genetics,” Gimenez-Roqueplo told Endocrine Today. “More than 15 paraganglioma and pheochromocytoma susceptibility genes were identified. A germline mutation in one of these genes can be identified in around 40% of the patients with paraganglioma and pheochromocytoma. Our data demonstrate, for the first time, that the identification of an SDHx or VHL germline mutation has a direct and a positive impact on the management and the clinical outcome of the affected patients.”
In a retrospective study, researchers analyzed data from 221 patients from 24 tertiary centers in France who had a diagnosis of paraganglioma or pheochromocytoma carrying a germline mutation in one of the four major susceptibility genes (SDHB, SDHD, SDHC and VHL). Researchers stratified the cohort into two groups. The genetic group was defined as patients who received results from genetic testing within 12 months of diagnosis of first paraganglioma or pheochromocytoma (n = 125; mean follow-up duration, 7 years). The historical group was defined as patients who received a genetic test retrospectively after at least 7 years of follow-up (n = 96; mean follow-up duration, 21 years).
Compared with historical patients, researchers found that patients in the genetic group underwent more examinations and were less likely to be lost to follow-up (9.6% vs. 72%; P < .0001). Additionally, 54% of patients in the historical group had no follow-up exams during their first 7 years after diagnosis, according to researchers.
Patients in the genetic group also experienced a less severe course of disease. Researchers observed smaller new metastases in genetic vs. historical patients (mean, 18.7 mm vs. 27.6 mm; P = .0128), as well as lower metastatic spread.
“Importantly, these differences were reversed in the historical cohort after genetic testing,” the researchers wrote.
The researchers also found that patients in the genetic group who developed metachronous metastases had better 5-year survival vs. historical patients (P = .0127).
“Physicians should be aware that our study reinforces the guidelines endorsed by the Endocrine Society and the European Society of Endocrinology that recommended proposing genetic testing to all patients with paraganglioma and pheochromocytoma at the time of the first diagnosis and shows the benefits of a regular surveillance for the clinical outcome of patients with genetically determined paraganglioma and pheochromocytoma,” Gimenez-Roqueplo said. “A genetic test should be offered to every patient with paraganglioma and pheochromocytoma. Every mutation carrier would be directed to a referral center with appropriate expertise to ensure a regular surveillance, and thereby, secure a favorable outcome.” – by Regina Schaffer
For more information:
Anne-Paule Gimenez-Roqueplo, MD, PhD, can be reached at Paris Descartes University, AP HP, Hôpital Européen Georges Pompidou, Genetics Department, INSERM, U970, Paris; email: email@example.com.
Disclosures: The authors report no relevant financial disclosures.