Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours

Abstract

Neuroendocrine tumours (NET) of the gastroenteropancreatic system comprise a malignant entity with a low incidence. Only limited information is available on long-term clinical outcome and clinically applicable prognostic factors. We performed a retrospective analysis of a large, wellcharacterized centre-based patient cohort of 399 patients with histologically proven NET. Data were analysed according to epidemiological, clinical and histopathological characteristics. Detailed survival analyses using the Kaplan-Meier method were performed. Prognostic factors were tested by log-rank testing and independent risk factors were analysed using a Cox regression model. In the studied cohort, primary tumours originated in the fore-, mid-and hindgut in 46.1, 37.1 and 4.5% respectively. Extra-intestinal or unknown primary tumours were present in 8.4 and 10.5% respectively. Distant metastasis was present at initial diagnosis in 69.4%. Most frequent metastatic sites were liver (85%), peritoneal cavity (18%), bones (8%), other intraabdominal sites (6%) and lungs (4%). Overall, 5-and 10-year survival rates were 78 and 63% respectively. Time to progression after initial diagnosis was significantly shorter in pancreatic as compared with ileal NET. Survival analysis revealed significantly better clinical outcome for primary tumours smaller than 25 mm, absence of metastasis, absence of any clinical symptoms, positive immunohistochemical staining for chromogranin A and a lower Ki67 index. These results were confirmed as independent by multivariate analysis. Therefore, this large retrospective analysis of a well-documented cohort of patients with NET demonstrates several prognostic factors of clinical relevance and wide availability, which should be considered for risk stratification in the management of NET.

Are G3 ENETS neuroendocrine neoplasms heterogeneous?

“…In addition, selection of patients was based on the requisite of a pathological review and an entire follow-up in our institution since diagnosis. This figure is in the upper range of previous publications using the same restrictive inclusion criteria, which reported a 6-33% frequency of G3 NEN according to ENETS proposals (Pape et al 2008, Niederle et al 2010 Panzuto et al 2011). The highest percentages were observed in two of these series in which untreated or metastatic GEP-NEN patients were enrolled , Panzuto et al 2011.…”

Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis

“…In European and American referral centers, up to 77 and 91 % of patients with PNETs and intestinal NETs [19][20][21][22] present with distant metastases at initial diagnosis, respectively [13]. In the present Japanese study, patients in whom distant metastases were observed at initial diagnosis accounted for 19.9 % of PNETs and 6.0 % of GI-NETs.…”

Inhibition of Peripheral Synthesis of Serotonin as a New Target in Neuroendocrine Tumors

“…Carcinoid syndrome has been reported to be present in 8%-35% of patients with NETs and is characterized by a wide range of symptoms, such as flushing episodes, diarrhea, abdominal pain, intermittent bronchial wheezing, telangiectasia, heart valve disease, mesenteric fibrosis, and pellagra [5,[9][10][11]. Carcinoid crisis is considered an immediate life-threatening complication of carcinoid syndrome due to a massive release of vasoactive peptides from the tumor.…”