Abstract
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 >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 ≥0.2 mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥3.0 cm (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 < 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.
Highlights
Pancreatic neuroendocrine neoplasms represent heterogeneous and rare tumors despite a rising incidence [1]
To investigate the underlying causal coherences of C-reactive Protein (CRP) and decreased overall survival (OS), we further investigated factors associated with recurrence
From clinical risk score (CRS):0 to CRS:3, each additional risk factor resulted in an increased probability of death (OS) during follow-up with an hazard ratios (HRs) of 2.62 (95%CI 1.91–3.60; p < 0.001) and pancreatic neuroendocrine neoplasms (panNEN)-related death (DSS) with an HR of 3.53 (95%CI 2.20–5.68; p < 0.001; Cox-proportional hazards regression)
Summary
Pancreatic neuroendocrine neoplasms (panNENs) represent heterogeneous and rare tumors despite a rising incidence [1]. Several risk-scoring systems have been proposed [7,8,9], and most of them are composed of factors not reliably available before surgery, e.g., lymph node positivity or microvascular/perineural invasion. For the prediction of postoperative morbidity, histological features, and estimated overall, disease-specific, and recurrence-free survival (OS, DSS, and RFS), a risk score with preoperative ideally non-invasively available factors is highly desirable for guidance of potential (neo-)adjuvant therapeutic concepts, especially in high-risk individuals [13,14]. Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs
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