Bone metastases (BM) in neuroendocrine neoplasms (NEN) represent a poorly defined issue.
This is a nationwide survey among Italian institutions dealing with NEN patients. Characteristics of BM, clinical management, skeletal related events (SREs) and disease outcome were recorded.
We analysed 321 patients with histological diagnosis of NEN and BM collected from 18 Italian Centers. Mean age was 59 y.o. (range 13-86). Primary sites were 47% gastroenteropancreatic (GEP), 36% lung, 4% Paraganglioma/Pheocromocytoma (Par/Pheo), 7% unknown, 5% others. The vast majority (72%) of NEN were already metastatic at diagnosis and the liver represented the second most frequent site of metastasis (in 77% of patients) during follow-up, in addition to BM. Bone was the first metastatic site in 41% of cases. Neoplasms were low/intermediate grade in 80% and high grade in 20%. SREs occurred in 32% of cases, mainly in lung and others. Median time to SRE was 4 months. It strictly correlated with the high grade, irrespective of the primary site. Bisphosphonates were administered in 32% of patients. Median survival from BM diagnosis was 65 months (range 45-78) in the whole population, with Par/Pheo at the best and high grade GEP at the worst limit. SRE, high grade (or in alternative high Ki-67) and prior lung metastases resulted significantly associated with worse overall survival at the multivariable analysis. After adjustment for tumor grade, survival of patients with GEP and lung NENs were similar.
This is one of the largest series of NEN patients with BM reported so far. This survey mirrors the Italian real clinical practice in this setting, as it included most Centers involved in NET patients’ management. It showed that overall, BM from NEN are associated with a relatively long survival. Bisphosphonates were used in a low percentage of cases, probably related to SRE. Tumor grade confirmed its value in separating two survival categories, irrespective of primary site. The results of this analysis generated hypotheses for prospective trials in homogeneous clinical settings.
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All authors have declared no conflicts of interest.