Endocrine Abstracts

Introduction: Neuroendocrine neoplasms (NENs) are neoplasms with a slow progression and a 5-year survival 77–95%. It is well known that secondary deposits of NENs may dedifferentiate during the natural history of the disease, presenting a more aggressive biological behaviour.

Aim of the study: The prevalence of secondary foci dedifferentiation of pancreatic NENs (p-NENs).

Methods: From the NENs database of 414 patients, 160 (38.6%) had pNENs. Patients with dedifferentiation were identified by a new biopsy of metastatic foci and a high proliferation index Ki-67 MIBI (%) that indicated a poorly differentiated NENs that originated from a primary site with a lower Ki-67.

Results: Five (3%) (mean age(±S.D.): 58.8±4.3 years, two males (40%)) patients, all with sporadic NENs presented dedifferentiation during the natural history of their disease as compared to 155 (52.9±15.8 years, 94 males (58.8%)) patients with NENs and no dedifferentiation (120 with sporadic NEN). At presentation, 1 patient had a stage III NEN, while 4 had a Stage IV NEN; 1 patient had Ki-67 1%, while 4 had 5% (grade 1 and 2, respectively) while when dedifferentiation was seen, 1 patient had Ki-67 30%, 2 had 50%, 1 had 60%, and 1 had 70%. At presentation, all five patients had metastases: 3 only liver metastases, 1 liver along with bone metastases and 1 liver along with ovaries and breast metastases; all 5 patients had a positive Octreoscan; 2 had a functional syndrome (one carcinoid syndrome and one insulinoma). At presentation 2 patients were candidates for a surgical approach. As first line treatment 2 patients received somatostatin analogs (SSAs) plus everolimus, 1 SSAs plus everolimus plus peptide receptor radionuclide therapy (PRRT), and 1 SSA monotherapy, while another one was followed-up without treatment. Progression free-survival (PFS) for 1st line treatment was 39.3±25.9 months, while PFS o further therapies varied from 13.4±11.2 months to 6.3±7.0 months (eight lines of treatment were registered). At the last follow-up, 3 (60%) patients were alive with an overall survival 158.73±50.91 months.

Conclusions: The dedifferentiation of NENs implies a more aggressive biological behaviour and worse overall survival despite the use of different therapies.