OC.01.4 PREDICTIVE VALUE OF PRE-OPERATIVE STAGING AND GRADING IN PANCREATIC NEUROENDOCRINE NEOPLASMS

Background and aim: Pancreatic NeuroEndocrine Tumors (P-NETs) are a heterogeneous group of neoplasms with highly variable clinical behavior.In the attempt to assess a better prognostic description, the European Neuroendocrine Tumors Society (ENETS) proposed a new grading and TNM-based staging system. Aims of this study were to compare pre-operative and postoperative Staging and Grading in P-NETs and their prognostic significance; to determine if a new cut-off value of Ki-67 proliferative index for P-NETs Grading can improve the accuracy of prognostic stratification. Material and methods: Our retrospective study is composed of 285 patients with P-NETs observed at San Raffaele Scientific Institute from 1988 to 2012. Out of these, 90 and 42, respectively, were classified according to a new presurgical classification, composed of pre-operative Staging (CT, MRI, EUS) and Grading (EUS-guided FNA and cytological Ki-67 evaluation).Comparison between pre and post-operative models (Pre-Stage vs. Stage e Pre-Grade vs. Grade) was possible for 88 and 33 neoplasms, respectively. Ki-67 proliferative index was evaluated through immunocytochemical (Pre-Grade) and immunohistochemical (Grade) analyses. Agreement between pre-operative and post-operative models was performed through k-statistics (Cohen). A p-value <0.05 was considered significant. Results: Among all pre-operative and post-operative models, Pre-Grade shows the highest Harrell’s C (0.97), resulting the best tool for a proper prognostic stratification. When comparing pre-operative and post-operative models, percent agreement between Pre-Stage and Stage was good (83%, k=0.74), otherwise agreement between Pre-Grade and Grade was moderate (70%, k=0.42), when used a 2% cut-off for Grade 1 tumor definition; contrarily, when used a 5% cut-off, Pre-Grade and Grade showed a good agreement (88%, k=0.66). The definition of a new 5% cut-off for cytological and histological Ki-67 index improved the accuracy of patients’ prognostic stratification, being not significant the difference between patients’ 10-year survival for Ki-67 levels within 5% (93.75% vs. 90%). Conclusions: The new proposed pre-surgical classification, based on PreStage and Pre-Grade, is comparable to post-surgical models. This system shows a good agreement with post-surgical one, being efficient in pre-surgical disease’s biology evaluation.