Predicting Recurrence-Free Survival in Patients with Well-Differentiated Pancreatic Endocrine Neoplasms without Distant Metastasis: WHO Classification or Two-Tier Grading System?
Ta-chiang Liu, Nicholas Hamilton, William G Hawkins, Dengfeng Cao. Washington University School of Medicine, St. Louis
Background: Well-differentiated pancreatic endocrine neoplasms (WDPENs) are uncommon. In the absence of metastasis or invasion, it is difficult to predict their behavior. This study is to compare the ability of two current grading systems, WHO classification and two-tier grading system, to predict recurrence-free survival (RFS) in patients with WDPENs but without distant metastasis (DM) at diagnosis.
Design: The following 11 parameters were analyzed in 94 patients: age, gender, tumor size, T stage, lymph node (LN) status, margin status, vascular invasion (VI), perineural invasion (PI), mitosis, necrosis, Ki-67 proliferation index. Each tumor was graded using the WHO classification [benign behavior (BB): confined to the pancreas, no VI, no PI, <2 mitoses/10HPFs, Ki-67 <2%; uncertain behavior (UB): confined to the pancreas and at least one of the following: ≥ 2 cm, 2-10 mitoses/10 high power fields (HPFs), Ki-67>2%, VI, PI; well-differentiated endocrine carcinoma (WDCA): gross local invasion or metastasis] and the two-tier grading system [low grade (LG): no necrosis and < 2 mitoses/50HPFs; intermediate grade (IntG): with necrosis or 2 to 50 mitoses/50HPFs]. These parameters and tumor grade were correlated with RFS using Kaplan-Meier method and log-rank test. Concordance-index (CI) was calculated for these 2 grading systems.
Results: The mean age (44 M, 50 F) at diagnosis was 53.7 years. The mean tumor size was 2.9 cm (40 T1, 29 T2, 25 T3). Positive margin, VI, PI, necrosis, and LN metastasis was seen in 16, 29, 22, 15, and 29 tumors, respectively. Mitosis was identified in 41 tumors (mean 3.9 per 50 HPFs). Twenty-one, 46, and 27 tumors fell into BB, UB, and WDCA categories, respectively. Sixty were LGs and 34 were IntGs. Average Ki-67 was 6.6%. During followup (1 to 212 months), 22 patients recurred (1/21 BBs, 9/46 UBs, 12/27 WDCAs; 6/60 LGs, 16/34 IntGs). Tumor size, T stage, node metastasis, VI, PI, Ki-67, necrosis, and mitosis strongly predicted RFS (p<0.01 for all) where age (p = 0.38), gender (p = 0.18), and margin status (p =0.53) did not. Both WHO classification and two-tier system strongly predicted RFS (p= 0.002 and 0.0003, respectively). The CI of the former was 0.69 whereas that of the latter was 0.73. When Ki-67 and the two-tier system were combined, the CI was 0.79.
Conclusions: The two-tier grading system is better than the WHO classification in predicting RFS in patients with WDPCAs without DM. Further predicting accuracy can be achieved by combining Ki-67 and the two-tier grading system.
Category: Liver & Pancreas
Monday, February 28, 2011 2:30 PM
Platform Session: Section D, Monday Afternoon