Article

Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumors

Department of Hepatology and Gastroenterology, Charité, Campus Virchow Klinikum, University Medicine Berlin, Berlin, Germany.
Endocrine Related Cancer (Impact Factor: 4.91). 08/2008; 15(4):1083-97. DOI: 10.1677/ERC-08-0017
Source: PubMed

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, well-characterized 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 intra-abdominal 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.

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    • "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, Hentic et al. 2011, "
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    ABSTRACT: The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung neuroendocrine carcinomas. We aim to characterize the subgroup of non-small cell type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathologic features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small cell type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Seventeen per cent (28 patients) fit with inclusion criteria. Tumors were classified as well differentiated NET (G3-WDNET) in 42.8% and poorly differentiated, large cell neuroendocrine carcinoma (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or NSE were elevated in 42% and 25%, respectively, of G3-WDNET and 31% and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88% and 50% of G3-WDNET or G3-LCNEC, respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P = 0.34). Short survival was observed in 25% of G3-WDNET but 62.5 % of G3- LCNEC patients (P = 0.049). We conclude that G3 ENETS GEP and thoracic NEN could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.
    Endocrine Related Cancer 07/2013; 20(5). DOI:10.1530/ERC-13-0027 · 4.91 Impact Factor
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    • "Published online 16 March 2010 & 2010 Cancer Research UK Keywords: chemotherapy; NETs; Ki-67; mitotic index Neuroendocrine tumours (NETs) are a heterogeneous group of malignancies that arise from various sites in the body, most commonly the gastrointestinal (GI) tract. The clinical course varies from a highly aggressive disease with a median survival of around 6 months in patients with metastatic high-grade tumours, to a more indolent process in which patients live with their disease for up to 20 years (Pape et al, 2008a, b; Yao et al, 2008). Recent data suggest that the incidence of NETs has increased fivefold over the past 30 years and is now 5.25 per 100 000. "
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    ABSTRACT: The role of chemotherapy for neuroendocrine tumours remains controversial and there is no standard regimen. We report the outcome for a consecutive series of chemonaive patients with metastatic or locally advanced neuroendocrine tumours treated with a combination of 5-fluorouracil (500 mg m(-2)), cisplatin (70 mg m(-2)) and streptozocin (1000 mg m(-2)) (FCiSt) administered three weekly for up to six cycles. Patients were assessed for radiological response, toxicity and survival. In the 79 patients assessable for response, treatment with FCiSt was associated with an overall response rate of 33% (38% for pancreatic primary sites and 25% for non-pancreatic primary sites). Stable disease occurred in a further 51%, with progression in 16%. The median time to progression was 9.1 months and median overall survival was 31.5 months. The most common grade 3-4 toxicity was neutropaenia (28% patients) but grade 3-4 infection was rare (7%). The most frequent non-haematological grade 3-4 toxicity was nausea and vomiting (17%). Prognostic factors included Ki-67, mitotic index, grade and chromogranin A, whereas response to chemotherapy was predicted by mitotic index, grade and alpha-fetoprotein. FCiSt is an effective regimen for neuroendocrine tumours with an acceptable toxicity profile. Grade and mitotic index are the best predictors of response.
    British Journal of Cancer 03/2010; 102(7):1106-12. DOI:10.1038/sj.bjc.6605618 · 4.82 Impact Factor
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    • "In another study of 399 patients, 37% of the patients were MNET's. This study found improved prognosis with primary tumours !2.5 cm, absence of liver metastases, absence of carcinoid symptoms and a low Ki67 (Pape et al. 2008). Two studies have identified that the prognosis of patients with MNETs is dependent on gender and presence of liver metastases (Burke et al. 1997, Tomassetti et al. 2006). "
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    ABSTRACT: We intended to identify the prognostic factors and the results of interventions on patients with liver metastatic midgut carcinoids. Five institutions that are part of United Kingdom and Ireland neuroendocrine tumour (NET) group took part in this study. Patients were included if they had histology proven NET of midgut origin and liver metastases at the time of the study. Clinical and biochemical data were collected retrospectively from hospital charts, pathology reports, radiology reports and biochemistry records for each patient. Three hundred and sixty patients were included in the study. The median survival from date of diagnosis was 7.69 years (confidence interval (CI) 6.40-8.99) and 5.95 years (CI 5.02-6.88) from date of diagnosis of liver metastases. On univariate analysis, increasing age at diagnosis, increasing urinary hydroxyindole acetic acid levels, increasing plasma chromogranin A levels, high Ki67, high tumour volume and treatment with chemotherapy were identified as factors associated with a significantly poorer outcome. Resection of liver metastases, resection of small bowel primary, treatment with somatostatin analogue therapy and treatment with peptide receptor therapy were associated with improved prognosis. Multivariate analysis revealed that age at diagnosis (P=0.014), Ki67 level (P=0.039) and resection of primary (P=0.015) were independent predictors of survival. This is the largest study to our knowledge looking specifically at the prognosis and clinical course of patients with liver metastatic midgut NETs. For the first time, we have shown that Ki67 and resection of primary are independent predictors of survival for this group of patients.
    Endocrine Related Cancer 06/2009; 16(3):885-94. DOI:10.1677/ERC-09-0042 · 4.91 Impact Factor
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