Endocrine Abstracts

Background: Paragangliomas(PGLs) and pheochromocytomas (PHEOs) are rare extra-adrenal neuroendocrine tumors of the sympathetic and parasympathetic nervous system. Metastatic status is defined by the abnormal presence of non-chromaffin tissue in extra adrenal organs. The incidence of metastases rises up to 10–17% and may appear even 10 years after the initial diagnosis.

Methods: We retrospectively analysed medical files of patients followed in a tertiary hospital (Center of excellence of rare adrenal diseases). Therapeutic modalities as well as mortality and progression status were recorded.

Results: Twenty seven patients diagnosed with metastatic PHEOs/PGL were included (mean±S.D. age in years: 39±15.6). Six patients presented with synchronous metastases and 21 patients developed metastases within a median time of 7 years of follow-up. The 60% of PHEOs and 40% of PGLs were functional. Genetic analysis was performed in 59% of the total included patients (n=2/12 patients with PHEOs and n=7/15 with PGLs) and was found positive in 9 patients (56%) (2 with SDHA, 1 with SDHB,5 with SDHD and 1 with EPAS1 mutation). Median PASS was 7 (min–max:1–9) for PHEOs and GAPP was 6 (min–max:4–7) for PGLs. Median Ki-67% index levels was 5 (min–max:-1–70). Median progression-free survival (PFS) for metastatic disease was 5.9 years (min:0.48-max:15.25) within a median follow-up time of 7 years. Local recurrence was treated either with radiotherapy in 6/27 patients or with second surgery in 10/27 patients, while 2 of them underwent also a third operation. In total, 12 patients were treated with chemotherapy (Cyclophospamide – vincristine -dacarbazine (CVD) or temozolomide) as first line treatment after surgery, n=6 with molecular targeted treatment (MTT) including sunitinib/ cabozatinib /pazopanib as second line and n=6 patients were treated with radiopeptides (PRRTS) or n=4 treated with MIBG analogues. The estimated median PFS was 5,39 months (min:3,02-max:55) for chemotherapy, 6.96 (min:2.76-max:55.68) for MTT, 7.9 (min:6.6-max:180) for radiopeptides and 36.6 (min:16.2-max:124.2) for MIBG therapy. Four patients were lost during follow-up. The observed mortality rate was 21%.

Conclusions: Metastatic PHEOs/PGLs are rare adrenal entities and their management remains challenging requiring a multidisciplinary decision. In most cases metastases occur many years after the initial diagnosis and often they require multiples lines of treatment. In our study, radiopeptides showed the longer PFS comparing with the other systematic treatments.