Wen-Quan Wang1,2,3,4, Wu-Hu Zhang1,2,3,4, He-Li Gao1,2,3,4, Dan Huang2,5, Hua-Xiang Xu1,2,3,4, Shuo Li1,2,3,4, Tian-Jiao Li1,2,3,4, Shuai-Shuai Xu1,2,3,4, Hao Li1,2,3,4, Jiang Long1,2,3,4, Long-Yun Ye1,2,3,4, Chun-Tao Wu1,2,3,4, Xuan Han1,2,3,4, Xiao-Hong Wang2,6, Liang Liu7,8,9,10, Xian-Jun Yu11,12,13,14. 1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 3. Shanghai Pancreatic Cancer Institute, Shanghai, China. 4. Pancreatic Cancer Institute, Fudan University, Shanghai, China. 5. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. 6. Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China. 7. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. liuliang@fudanpci.org. 8. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. liuliang@fudanpci.org. 9. Shanghai Pancreatic Cancer Institute, Shanghai, China. liuliang@fudanpci.org. 10. Pancreatic Cancer Institute, Fudan University, Shanghai, China. liuliang@fudanpci.org. 11. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. yuxianjun@fudanpci.org. 12. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. yuxianjun@fudanpci.org. 13. Shanghai Pancreatic Cancer Institute, Shanghai, China. yuxianjun@fudanpci.org. 14. Pancreatic Cancer Institute, Fudan University, Shanghai, China. yuxianjun@fudanpci.org.
Abstract
BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. METHODS: We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. RESULTS: PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5 years) of PanNETs after curative resection (P = 0.019, P < 0.001, and P < 0.001, respectively). Using these factors, we established a novel risk factor panel (R-panel), which predicted early recurrence (P < 0.001, HR = 15.02, 95% CI 5.76-39.19). Predictive accuracy of this R-panel was favorable, with a C-index of 0.853, higher than AJCC TNM staging (0.713). We further built an integrated staging system combining R-panel scoring and TNM staging, which improved predictive probability of TNM staging. Finally, we showed that adjuvant therapy with long-acting somatostatin analogs (SSAs) significantly reduced postoperative recurrence (P < 0.001) and prolonged long-term survival (P = 0.021) in patients with the above risk factors. CONCLUSION: We identified a novel risk factor panel, which includes PanNET G3, pancreatic duct dilatation, and perineural invasion; this panel predicted early recurrence of PanNETs after curative resection. Patients with these risk factors can benefit from adjuvant therapy with SSAs.
BACKGROUND:Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. METHODS: We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. RESULTS: PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5 years) of PanNETs after curative resection (P = 0.019, P < 0.001, and P < 0.001, respectively). Using these factors, we established a novel risk factor panel (R-panel), which predicted early recurrence (P < 0.001, HR = 15.02, 95% CI 5.76-39.19). Predictive accuracy of this R-panel was favorable, with a C-index of 0.853, higher than AJCC TNM staging (0.713). We further built an integrated staging system combining R-panel scoring and TNM staging, which improved predictive probability of TNM staging. Finally, we showed that adjuvant therapy with long-acting somatostatin analogs (SSAs) significantly reduced postoperative recurrence (P < 0.001) and prolonged long-term survival (P = 0.021) in patients with the above risk factors. CONCLUSION: We identified a novel risk factor panel, which includes PanNET G3, pancreatic duct dilatation, and perineural invasion; this panel predicted early recurrence of PanNETs after curative resection. Patients with these risk factors can benefit from adjuvant therapy with SSAs.