A tool to predict survival in stage IV entero-pancreatic NEN
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ORIGINAL ARTICLE
A tool to predict survival in stage IV entero‑pancreatic NEN M. Tarquini1 · M. R. Ambrosio1,2 · M. Albertelli3 · P. B. de Souza1 · R. Gafà4 · I. Gagliardi1 · A. Carnevale5 · P. Franceschetti2 · M. C. Zatelli1,2 Received: 27 July 2020 / Accepted: 22 August 2020 © The Author(s) 2020
Abstract Purpose Well-differentiated stage IV neuroendocrine neoplasms (NEN) have an extremely heterogeneous, unpredictable clinical behavior. Survival prognostic markers, such as the recently proposed NEP-Score, would be very useful for better defining therapeutic strategies. We aim to verify NEP-Score applicability in an independent cohort of stage IV well-differentiated (WD) gastroentero-pancreatic (GEP) NEN, and identify a derivate prognostic marker taking into account clinical and pathological characteristics at diagnosis. Methods Age, site of primary tumor, primary tumor surgery, symptoms, Ki67, timing of metastases of 27 patients (10 females; mean age at diagnosis 60.2 ± 2.9 years) with stage IV WD GEP NEN were evaluated to calculate the NEP-Score at the end of follow-up (NEP-T). We calculated the NEP-Score at diagnosis (NEP-D), which does not consider the appearance of new metastases during follow-up. Patients were subdivided according to whether they were alive or not at the end of follow-up (EOF) and an NEP-Score threshold was investigated to predict survival. Results Mean NEP-T and mean NEP-D were significantly lower in 15 live patients as compared to 12 deceased patients (p 70% survival; patients at intermediate risk (70 20 Timing of metastases Synchronous Metachronous > 24 months Metachronous ≤ 24 months
0 28 58 0 59 0 100 32 0 0 12 57 0 38 72
Table 2 Patients’ general features
Gender Males Females Primary tumor site Ileum Pancreatic Metastasis timing Synchronous Metachronous Ki67 (Mib-1) 0–2 3–20 > 20 Functional status No Yes Primary tumor surgery No Yes Alive at EOF No Yes
number
%
17 10
63 37
13 14
48 52
12 15
44 56
17 7 3
63 26 11
18 9
67 33
6 21
22 78
12 15
44 56
Journal of Endocrinological Investigation
the 2019 WHO classification of tumors of the digestive system. Among these patients, 55% patients had documented progressive disease at the time of score calculation at diagnosis. All of them had been treated with long-acting somatostatin analogs and two patients with insulinoma had been treated with everolimus. Patients were evaluated for the following characteristics to calculate the NEP-Score at the end of follow-up (NEP-T) which lasted 70.3 ± 11.6 months: age, site of primary tumor, primary tumor surgery, symptoms, grading, timing of metastases, assigning the respective scores (see Table 1). A modified NEP-Score was then calculated, considered as the NEP-Score at diagnosis (NEP-D), which does not take into account the appearance of new metastases during follow-up. Patients were subdivided according to whether they were alive or not at the end of follow-up (EOF). Patient characteristics are displayed in Table 2 and in Supplemetary Table 1. This study
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