Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67.

BACKGROUND: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. METHODS: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0-5 and Ki67 6-20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. RESULTS: The study enrolled 241 patients (86%) with Ki67 0-5% and 39 patients (14%) with Ki67 6-20%. Recurrence was seen in 34 patients (14%) with Ki67 0-5% after a median period of 34 months and in 16 patients (41%) with Ki67 6-20% after a median period of 16 months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0-5% and respectively 55 and 26% for Ki67 6-20% (p < 0.001). The overall survival period after recurrence was 44.9 months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4 cm and lymph node metastases were independently associated with recurrence. CONCLUSIONS: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed.

A Nationwide Population-Based Study on the Survival of Patients with Pancreatic Neuroendocrine Tumors in The Netherlands.

BACKGROUND: Large population-based studies give insight into the prognosis and treatment outcomes of patients with pancreatic neuroendocrine tumors (pNETs). Therefore, we provide an overview of the treatment and related survival of pNET in the Netherlands. METHODS: Patients diagnosed with pNET between 2008 and 2013 from the Netherlands Cancer Registry were included. Patient, tumors and treatment characteristics were reported. Survival analyses with log-rank testing were performed to compare survival. RESULTS: In total, 611 patients were included. Median follow-up was 25.7 months, and all-cause mortality was 42%. Higher tumor grade and TNM stage were significantly associated with worse survival in both the overall and metastasized population. The effect of distant metastases on survival was more significant in lower tumor stages (T1-3 p < 0.05, T4 p = 0.074). Resection of the primary tumor was performed in 255 (42%) patients. Patients who underwent surgery had the highest 5-year survival (86%) compared to PRRT (33%), chemotherapy (21%), targeted therapy and somatostatin analogs (24%) (all p < 0.001). Patients with T1M0 tumors (n = 115) showed favorable survival after surgical resection (N = 95) compared to no therapy (N = 20, p = 0.008). Resection also improved survival significantly in patients with metastases compared to other treatments (all p > 0.05). Without surgery, PRRT showed the best survival curves in patients with distant metastases. Grade 3 tumors and surgical resection were independently associated with survival (HR 7.23 and 0.12, respectively). CONCLUSION: Surgical resection shows favorable outcome for all pNET tumors, including indolent tumors and tumors with distant metastases. Prospective trials should be initiated to confirm these results.