TY - JOUR
T1 - A preoperative clinical risk score including c-reactive protein predicts histological tumor characteristics and patient survival after surgery for sporadic non-functional pancreatic neuroendocrine neoplasms: An international multicenter cohort study
AU - Primavesi, Florian
AU - Andreasi, Valentina
AU - Hoogwater, Frederik J. H.
AU - Partelli, Stefano
AU - Wiese, Dominik
AU - Heidsma, Charlotte
AU - Cardini, Benno
AU - Klieser, Eckhard
AU - Marsoner, Katharina
AU - Fröschl, Uwe
AU - Thalhammer, Sabine
AU - Fischer, Ines
AU - Göbel, Georg
AU - Hauer, Andreas
AU - Kiesslich, Tobias
AU - Ellmerer, Philipp
AU - Klug, Reinhold
AU - Neureiter, Daniel
AU - Wundsam, Helwig
AU - Sellner, Franz
AU - Kornprat, Peter
AU - Függer, Reinhold
AU - Öfner, Dietmar
AU - Nieveen van Dijkum, Elisabeth J. M.
AU - Bartsch, Detlef K.
AU - de Kleine, Ruben H. J.
AU - Falconi, Massimo
AU - Stättner, Stefan
N1 - Funding Information: Funding: This research received no external funding. The APC was funded by the Open Access Publication Fund of Medical University of Innsbruck. PhD Scholarship of Dr. Valentina Andreasi was supported by Gioja Bianca Costanza Legacy Fund. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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 ≥0.2mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥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 < 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.
AB - 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 ≥0.2mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥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 < 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.
KW - C-reactive protein
KW - Neuroendocrine neoplasms
KW - Pancreas
KW - Pancreatic neuroendocrine tumors
KW - Risk score
KW - Surgery
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85085088250&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers12051235
DO - https://doi.org/10.3390/cancers12051235
M3 - Article
C2 - 32423000
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 5
M1 - 1235
ER -