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Survival Following Resection of Well-Differentiated Pancreatic Neuroendocrine Tumors: Examining the New 2010 Who Classification
Toshiyuki Moriya*1,2, Timothy R. Donahue2, Oscar J. Hines2, James J. Farrell3, Howard a. Reber2, David Dawson4
1First Department of Surgery, Yamagata University, Yamagata, Japan; 2Department of Surgery, University of California Los Angeles, Los Angeles, CA; 3Department of Medicine, University of California Los Angeles, Los Angeles, CA; 4Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA
Introduction: In 2010 the WHO adopted a new grading system for neuroendocrine neoplasms (NET) of foregut origin based on proliferation determined by mitotic count and Ki67 index. Using a large single-institution cohort of resected pancreatic NETs (PNETs), we have retrospectively examined the prognostic value of the WHO 2010 classification system, the prior WHO classification system and AJCC stage for well-differentiated neuroendocrine tumors of the pancreas.
Methods: Search of pathology archives identified 114 patients who underwent pancreatic resection for PNETs at UCLA Medical Center from 1991-2009. Retrospective review of medical, surgical, and pathology databases was performed. Correlations between patient survival and various clinicopathologic factors were determined.
Results: By univariate analysis, significant predictors of disease-specific survival (DSS) in PNETs included positive margin status (p=0.019, HR 7.73, 95%CI [1.392-43.01]), and AJCC stage (Stage I, IIA versus IIB, IV, p=0.043, HR 6.87, 95% CI [1.06-37.41]). Individually, tumor size, perineural invasion, vascular invasion and functional tumor status were not significant predictors of DSS in the patient cohort. In our cohort, the new WHO 2010 classification scheme did not significantly predict DSS for well-differentiated PNETs (G1 PNETs versus G2 PNETs, p=0.085, HR 5.35, 95% CI [0.60-48.10]). In contrast, the prior WHO 2000 classification scheme was a significant predictor of DSS (1.0 + 1.1 PNETs versus 2.0 PNETs, p=0.048, HR 6.90, 95% CI [1.12-39.62]). We also examined whether WHO 2010 classification and AJCC staging parameters could be used in combination to better stratify patients into groups of variable prognostic significance. In stratified analysis of those patients with node-positive disease, G1 vs. G2 status showed a non-significant trend towards predicting patient survival after resection (p=0.13, HR 5.2, 95%CI [0.6-43.9]).
Conclusions: Consideration of both AJCC staging parameters and WHO 2010 G grade may be useful for the accurate prediction of DSS in resected, well-differentiated PNET, particularly for those patients with node-positive disease. Our findings in this retrospective analysis of a single institution cohort of PNET warrant further prospective analysis in a larger patient cohort.
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