Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas

Fischer, Lars; Kleeff, Jörg; Espósito, Irene; Hinz, Ulf; Zimmermann, Arthur; Friess, Helmut; Büchler, Markus W.

doi:10.1002/bjs.6051

Cited by 234 publications

(155 citation statements)

References 61 publications

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“…[16][17][18][19] Ekeblad et al 16 reported the analysis of 324 pancreatic endocrine tumors for which diagnosis according to WHO was available in only 241, whereas TNM data were available for 302 and grading for 93 patients. The study did not show any difference between stages I vs II or III, and only demonstrated a significant difference between stage IV (metastatic disease) vs any stage.…”

Section: Discussionmentioning

confidence: 99%

“…15 The validation of these TNM and grading systems has been variably addressed in four recent studies that all evidenced clear-cut distinctions only between higher and lower stages while they were of little help for intermediate-stage diseases. [16][17][18][19] There is clearly the need of a system permitting the prognostic stratification of all pancreatic endocrine tumor patients, including both those who may benefit from radical surgery and those with more advanced disease that cannot be resected.…”

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Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

et al. 2010

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Pancreatic endocrine tumors are rare diseases and devising a clinically effective prognostic stratification of patients is a major clinical challenge. This study aimed at assessing whether the tumor-node-metastasis (TNM)-based staging and proliferative activity-based grading recently proposed by the European NeuroEndocrine Tumors Society (ENETS) have clinical value. TNM was applied to 274 patients with histologically diagnosed pancreatic endocrine tumors operated from 1991 to 2005, with last follow-up at December 2007. According to World Health Organization (WHO) classification, 246 were well-differentiated neoplasms (51 benign, 56 uncertain behavior, 139 carcinomas) and 28 poorly differentiated carcinomas. Grading was based on Ki67 immunohistochemistry. Survival analysis not only ascertained the prognostic value of the TNM system but also highlighted that in the absence of nodal and distant metastasis, infiltration and tumor dimensions over 4 cm had prognostic significance. T parameters were then appropriately modified to reflect this weakness. The 5-year survival for modified TNM stages I, II, III and IV were 100, 93, 65 and 35%, respectively. Multivariate analysis identified TNM stages as independent predictors of death, in which stages II, III and IV showed a risk of death of 7, 29 and 58 times higher than stage I tumors (Po0.0001). Ki67-based grading resulted an independent predictor of survival with cut-offs at 5 and 20%. In conclusion, WHO classification assigns clinically significant diagnostic categories to pancreatic endocrine tumors that need prognostic stratification by applying a staging system. The ENETS-TNM provides the best option, but it requires some modifications to be fully functional. The modified TNM described in this study ameliorates the clinical applicability and prediction of outcome of the ENETS-TNM; it (i) assigns a risk of death proportional to the stage at the time of diagnosis, and (ii) allows a clinically based staging of patients, as the T parameters as modified permit their clinical-radiological recognition. Ki67-based grading discerns prognosis of patients with same stage diseases. Modern Pathology (2010) 23, 824-833; doi:10.1038/modpathol.2010 published online 19 March 2010 Keywords: pancreas; tumors; endocrine; staging; TNM; grading; prognosis Pancreatic endocrine tumors are rare and clinically taxing diseases, as their natural history is largely unknown. 1-4 Affected patients seek medical assistance due to symptoms resulting from either hormonal hypersecretion or mass. Thus, pancreatic endocrine tumors are clinically defined as functioning or nonfunctioning depending on the presence of a syndrome related to inappropriate hormone secretion. Such distinction, however, does not provide prognostic information. Pancreatic endocrine tumors are histologically divided into well-

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Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

et al. 2010

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“…At the time of presentation, patients may have symptoms related to tumor bulk or, in 20%-50% of cases, hormone production [6,8,9]. The likelihood of presenting with hormone-related symptoms depends on the site of tumor origin, with PNETs and midgut carcinoids (jejunum, ileum, appendix, and proximal colon) being more likely to present with symptoms than carcinoids arising from the foregut (lungs, thymus, stomach, and duodenum) or hindgut (distal colon and rectum).…”

Section: Epidemiology Clinical Presentation and Stagingmentioning

confidence: 99%

A New Era for the Systemic Therapy of Neuroendocrine Tumors

Eads

2012

The Oncologist

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After completing this course, the reader will be able to:1. Describe the underlying biology of neuroendocrine tumors including pancreatic neuroendocrine tumors (PNETs) and carcinoids and the importance of these biologic features in the evolution of new drugs for these diseases.2. Cite the historical data regarding the use of cytotoxic agents in the treatment of pancreatic neuroendocrine tumors and carcinoids.3. Explain the significance of recent clinical trials utilizing biologic agents, in particular octreotide, the small molecule tyrosine kinase inhibitor, sunitinib and the mammalian target of rapamycin (mTOR) inhibitor, everolimus, and how these medications have altered the natural history of both pancreatic neuroendocrine tumors and carcinoids.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTCarcinoids and pancreatic neuroendocrine tumors are becoming increasingly common, with the majority of patients presenting with either lymph node involvement or metastatic disease. An improved understanding of the molecular mechanisms involved in these tumors has implicated several pathways that have led to new therapeutic approaches. In this manuscript, we describe the biology of neuroendocrine tumors and approaches to systemic therapy. We review early data regarding the use of cytotoxics and several recent studies employing more targeted approaches that promise to change the standard of care. Specifically, phase III studies indicate that pharmacologic inhibition of the vascular endothelial growth factor pathway with sunitinib, and of the mammalian target of rapamycin pathway with everolimus, appears to have altered the natural history of these diseases. These successes set the stage for further advances in the management of patients with neuroendocrine tumors. The Oncologist 2012; 17:326 -338Correspondence: Neal J. Meropol, M.D.,

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“…More recently, lymph node metastases (Hellman et al 2002, Cardillo et al 2004, Lim et al 2005, Tomassetti et al 2005, Baudin 2007, García-Yuste et al 2007, Rea et al 2007, Pape et al 2008 and proliferative index have emerged as major determinant of prognosis in GEP tumors of the lung (Travis et al 1998, Beasley et al 2000, Lim et al 2005, Asamura et al 2006, Baudin 2007 stomach and pancreas (Chaudhry et al 1992, Pelosi et al 1996, Rindi et al 1999, Rigaud et al 2001, Hochwald et al 2002. At the end, a new classification emphasizing the role of TNM (Tumor, Nodes, Metastases) classification and proliferative index has emerged (Rindi et al 2006, 2007, Bettini et al 2008, Fischer et al 2008.…”

Section: Introductionmentioning

confidence: 99%

Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma

Durante¹,

Boukheris²,

Dromain³

et al. 2009

Endocrine-Related Cancer

104

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Survival of metastatic gastroenteropancreatic well-differentiated endocrine carcinoma (GEP WDEC) is not well characterized. We evaluated the long-term outcome and prognostic factors for survival in 118 patients with distant metastases from GEP WDEC. Inclusion criteria were 1) pathological review by a single pathologist according to the present WHO criteria, 2) absence of previous therapy apart from surgery, 3) complete morphological evaluation within 3 months including somatostatin receptor scintigraphy, and 4) follow-up at Gustave-Roussy Institute until death or study's end. Clinical, biological marker, and pathological parameters were analyzed in univariate and multivariate statistical models. Survival after the first complete imaging work-up of the metastatic disease was determined using Kaplan-Meier method. Overall, survival for 5 years after the diagnosis of metastatic disease was 54%. In multivariate analysis, age (hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.01-1.08, PZ0.01), the number of liver metastases (HR: 3.4, 95% CI: 1.4-8.3, PZ0.01), tumor slope (HR: 1.1, 95% CI: 1.0-1.1, PZ0.001), and initial surgery (HR: 0.3, 95% CI: 0.1-0.8, PZ0.01) were predictive of survival. Five-year survival was 100%, 91% (95% CI, 51-98%), 62% (95% CI, 37-83%), and 9% (95% CI, 6-32%) when patients had 0, 1, 2, 3 or more poor prognostic features respectively. This study enables the stratification of metastatic GEP WDEC patients into distinct risk groups. These risk categories can be used to tailor therapeutic approaches and also to design and interpret clinical trials.

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Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas

Abstract: Both classifications accurately reflect the clinical outcome of patients with pNET. The resection status may not be critical for long-term survival in patients with pNET.

Cited by 234 publications

References 61 publications

Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

A New Era for the Systemic Therapy of Neuroendocrine Tumors

Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma

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