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Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients &gt, 60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off &ge, 0.2mg/dL, hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size &ge, 3.0cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p &lt, 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.

Simple Summary Approximately 30% of patients with a pancreatic neuroendocrine tumor (pNET) will develop metastases. Curative-intent treatment largely involves resection. Identifying patients with early recurrence (ER) following resection might help tailor adjuvant therapies and the surveillance intensity. The aim of this retrospective study was to determine an evidence-based cut-off value for ER, and to explore risk factors associated with ER. ER was identified 18 months after surgery. Tumor size (OR 1.20, 95% CI 1.05–1.37, p = 0.007) and positive lymph nodes (OR 4.69, 95%CI 1.41–15.58, p = 0.01) were independently associated with ER. Patients with ER had lower post-recurrence free survival and overall survival than patients with late recurrence. These data support intensive follow-up shortly after surgery, and adjuvant therapy may help improve survival in pNET patients with ER after surgery. Abstract Background: Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting. Methods: Patients undergoing surgical resection for pNETs between 1998–2018 were identified using a multi-institutional database. Using a minimum p-value approach, optimal cut-off value of recurrence-free survival (RFS) was determined based on the difference in post-recurrence survival (PRS). Risk factors for early recurrence were identified. Results: Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest p-value of 0.019). Median RFS was 11.0 months (95% 8.5–12.60) among ER patients (n = 49) versus 41.0 months (95% CI: 35.0–45.9) among non-ER patients (n = 77). Median PRS was worse among ER patients compared with non-ER patients (42.6 months vs. 81.5 months, p = 0.04). On multivariable analysis, tumor size (OR: 1.20, 95% CI: 1.05–1.37, p = 0.007) and positive lymph nodes (OR: 4.69, 95% CI: 1.41–15.58, p = 0.01) were independently associated with ER. Conclusion: An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years after surgery.