Long-term outcomes and prognostic factors in 78 Japanese patients with advanced pancreatic neuroendocrine neoplasms: a single-center retrospective study

Abstract

Objective: Despite an increase in the number of Japanese patients with pancreatic neuroendocrine neoplasms, long-term outcomes and prognostic factors, especially for those with advanced disease, remain unclear.

Methods: We retrospectively reviewed the medical records of 78 patients with unresectable pancreatic neuroendocrine neoplasms treated at our hospital from January 1987 to March 2015. Survival analyses were performed using Kaplan-Meier methods. Prognostic significance of several clinicopathological factors were analyzed by univariate and multivariate analyses using a Cox regression model.

Results: Median overall survivals of pancreatic neuroendocrine tumor (n = 64) and pancreatic neuroendocrine carcinoma (n = 14) were 83.7 and 9.1 months, respectively (hazard ratio: 0.02, 95% confidence interval: 0.01-0.08, P < 0.001). Although no significant differences were observed using a Ki-67 cut-off value of 2% (hazard ratio: 0.46, 95% confidence interval: 0.16-1.13, P = 0.0989), a Ki-67 cut-off of 10% was a significant predictor in patients with pancreatic neuroendocrine tumor (hazard ratio: 9.95, 95% confidence interval, 3.01-32.97, P < 0.001). Treatment after the advent of targeted therapy (hazard ratio: 0.07, 95% confidence interval: 0.03-0.19, P < 0.001) and the presence of bone metastases (hazard ratio: 4.38, 95% confidence interval: 1.42-11.29, P = 0.013) were significant prognostic factors in patients with pancreatic neuroendocrine tumor evaluated by univariate analysis. Multivariate analysis also revealed that a Ki-67 index ≥10% (hazard ratio: 38.8, 95% confidence interval: 8.42-226.62, P < 0.001), approval of targeted therapy (hazard ratio: 0.02, 95% confidence interval: 0.00-0.11, P < 0.001) and bone metastases (hazard ratio: 5.56, 95% confidence interval: 1.10-24.00, P = 0.039) were independent prognostic factors.

Conclusions: We elucidated the long-term outcomes and prognostic factors in Japanese patients with advanced pancreatic neuroendocrine neoplasms.

Keywords: Ki-67 index; pancreatic neuroendocrine carcinoma; pancreatic neuroendocrine neoplasms; pancreatic neuroendocrine tumor; prognostic factor.

Figure 1.

Kaplan–Meier analyses of overall survival. (a) Overall survival in patients with pancreatic neuroendocrine tumor (PNET) and pancreatic neuroendocrine carcinoma (PNEC). Survival comparison using the Ki-67 cut-off values of 2% (b), 5% (c) and 10% (d) in patients with PNET, and 55% in patients with PNEC (e).

Figure 2.

Kaplan–Meier analyses of different prognostic factors. Overall survival in patients with advanced PNET according to bone metastases (a) and treatment timing (b).