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Vol. 98, No. 2, 2013
Issue release date: October 2013
Neuroendocrinology 2013;98:156-168

Prognostic Factors and Long-Term Outcome of Pancreatic Neuroendocrine Neoplasms: Ki-67 Index Shows a Greater Impact on Survival than Disease Stage. The Large Experience of the Spanish National Tumor Registry (RGETNE)

Martin-Perez E. · Capdevila J. · Castellano D. · Jimenez-Fonseca P. · Salazar R. · Beguiristain-Gomez A. · Alonso-Orduña V. · Martinez del Prado P. · Villabona-Artero C. · Diaz-Perez J.A. · Monleon A. · Marazuela M. · Pachon V. · Sastre-Valera J. · Sevilla I. · Castaño A. · Garcia-Carbonero R.
Departments of aSurgery, University Hospital La Princesa, Madrid, bMedical Oncology, University Hospital Vall d'Hebron, Barcelona, cMedical Oncology, University Hospital 12 de Octubre, Madrid, dMedical Oncology, Hospital Central de Asturias, Oviedo, eMedical Oncology, Hospital Duran i Reynals, Institut Catalá d'Oncologia, Barcelona, fSurgery, Hospital de Donostia, San Sebastian, gMedical Oncology, Hospital Miguel Servet, Zaragoza, hMedical Oncology, Hospital de Basurto, Vizcaya, iEndocrinology, Hospital de Bellvitge, Barcelona, jEndocrinology, University Hospital Clinico San Carlos, Madrid, kStatistics, Faculty of Biology, Barcelona University, Barcelona, lEndocrinology, University Hospital La Princesa, Madrid, mMedical Oncology, Hospital Ramon y Cajal, Madrid, nMedical Oncology, University Hospital Clinico San Carlos, Madrid, oMedical Oncology, Hospital Virgen de la Victoria, Malaga, pPathology, University Hospital Fuenlabrada, Madrid, and qMedical Oncology, University Hospital Virgen del Rocio, Institute de Biomedicina de Sevilla (IBIS), HUVR, CSIC, Universidad de Sevilla, Sevilla, Spain

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Introduction: Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival. Methods: From June 2001 through October 2010, 1,271 patients were prospectively registered online ( at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses. Results: Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome. Conclusion: Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients.

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