Pape UF, Berndt U, Muller-Nordhorn J, Bohmig M, Roll S, Koch M, Willich SN, Wiedenmann B. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer. 15: 1083-1097

Department of Hepatology and Gastroenterology, Charité, Campus Virchow Klinikum, University Medicine Berlin, Berlin, Germany.
Endocrine Related Cancer (Impact Factor: 4.81). 08/2008; 15(4):1083-97. DOI: 10.1677/ERC-08-0017
Source: PubMed


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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    • "Published data other than from the SEER database include a series of over 900 patients in whom the median OS was 7.9 years (94 months) for advanced small bowel NET and 3.9 years (46.8 months) for advanced panNET (Ter-Minassian et al, 2013), while another of 399 patients (Pape et al, 2008) showed a median OS of metastatic patients of estimated median survival for NET-related death according to the Kaplan–Meier analysis was 169 months. However, a number of such studies review prognostic factors related to the patient and tumour but do not report the variety of treatment modalities employed or provide any comparisons. "
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    ABSTRACT: Background: 131I-meta-iodobenzylguanidine (131I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae. Methods: Fifty-eight patients with metastatic NETs and CCTs who had received 131I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated. Results: In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of 131I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of 131I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function. Conclusion: Long follow up of 131I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.
    Full-text · Article · Jul 2013 · British Journal of Cancer
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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.
    Full-text · Article · Jul 2013 · Endocrine Related Cancer
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    • "NEBC has been reported to display strong ER and PR positivity and CerbB-2 negativity[6],[21], which was consistent with our observations. Ki-67 has been extensively reported as an important prognostic factor in other breast cancers and gastroenteropancreatic neuroendocrine tumors[22],[23]. In our study, Ki-67 immunostaining was observed in 10 NEBCs. "
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    ABSTRACT: To determine and quantitate the mammography and sonography characteristics in 13 cases of solid breast neuroendocrine carcinoma, and to correlate the radiological findings with the clinical and histopathological findings. The clinical data, mammography findings in 10, and sonography findings in 9 of 13 female patients with histologically confirmed solid breast neuroendocrine carcinoma were retrospectively reviewed. All imaging data were consensually evaluated by two radiologists. All cases presented with one palpable mass with only 1 patient experienced occasional breast pain and 5 complaint fluid discharge. In seven of the 13 cases, the masses were firm and mobile on physical examination. Regional lymph node metastasis was noted in only 1 patient. The mammographic findings were a mass in 6, clustered small nodules with clustered punctuate microcalcification in 1, asymmetric focal density in 2, and solitary punctuate calcification in 1 of the 10 patients. Most masses had irregular shape with indistinct or microlobulated margins. Ultrasonography(US) depicted 9 masses in 9 patients, all of which were hypoechoic, mostly with irregular shape, and without acoustic phenomenon, different kinds of acoustic phenomena also exist.1 patient developed distant metastasis at follow-up. Neuroendocrine breast carcinoma has a variety of presentations, but it is mostly seen on mammography as a dense, irregular masses with indistinct or microlobulated margins. Sonographically, they mostly present as irregular heterogeneously hypoechoic masses with normal sound transmission. Nipple discharge in the history and calcification in imaging were not rare.
    Full-text · Article · May 2012 · Chinese journal of cancer
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