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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 †

1
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
2
Pancreatic Surgery, Università Vita-Salute, IRCCS Hospital San Raffaele, 20132 Milan, Italy
3
Department of Surgery, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
4
Department of Visceral, Thoracic, and Vascular Surgery, University Hospital Marburg, 35043 Marburg, Germany
5
Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
6
Institute of Pathology, Paracelsus Medical University, 5020 Salzburg, Austria
7
Department of Surgery, Medical University Graz, 8036 Graz, Austria
8
Department of Surgery, Ordensklinikum, 4010 Linz, Austria
9
Department of Surgery, Kaiser Franz Josef Hospital, 1100 Vienna, Austria
10
Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, 6020 Innsbruck, Austria
11
Department of Surgery, General Hospital Horn, 3580 Horn, Austria
12
Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria
13
Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
This study has in part been presented as an abstract at the 2019 E-AHPBA Congress in Amsterdam, The Netherlands (abstract published in European Journal of Surgical Oncology. 2019;45, e72) and the Austrian Surgical Congress 2019 in Innsbruck, Austria (abstract published in European Surgery, Volume 51, May 2019, Supplement 1).
Cancers 2020, 12(5), 1235; https://doi.org/10.3390/cancers12051235
Received: 13 April 2020 / Revised: 1 May 2020 / Accepted: 12 May 2020 / Published: 14 May 2020
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. View Full-Text
Keywords: pancreatic neuroendocrine tumors; C-reactive protein; risk score; neuroendocrine neoplasms; pancreas; surgery; survival pancreatic neuroendocrine tumors; C-reactive protein; risk score; neuroendocrine neoplasms; pancreas; surgery; survival
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MDPI and ACS Style

Primavesi, F.; Andreasi, V.; Hoogwater, F.J.H.; Partelli, S.; Wiese, D.; Heidsma, C.; Cardini, B.; Klieser, E.; Marsoner, K.; Fröschl, U.; Thalhammer, S.; Fischer, I.; Göbel, G.; Hauer, A.; Kiesslich, T.; Ellmerer, P.; Klug, R.; Neureiter, D.; Wundsam, H.; Sellner, F.; Kornprat, P.; Függer, R.; Öfner, D.; Nieveen van Dijkum, E.J.M.; Bartsch, D.K.; de Kleine, R.H.J.; Falconi, M.; Stättner, S. 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. Cancers 2020, 12, 1235. https://doi.org/10.3390/cancers12051235

AMA Style

Primavesi F, Andreasi V, Hoogwater FJH, Partelli S, Wiese D, Heidsma C, Cardini B, Klieser E, Marsoner K, Fröschl U, Thalhammer S, Fischer I, Göbel G, Hauer A, Kiesslich T, Ellmerer P, Klug R, Neureiter D, Wundsam H, Sellner F, Kornprat P, Függer R, Öfner D, Nieveen van Dijkum EJM, Bartsch DK, de Kleine RHJ, Falconi M, Stättner S. 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. Cancers. 2020; 12(5):1235. https://doi.org/10.3390/cancers12051235

Chicago/Turabian Style

Primavesi, Florian, Valentina Andreasi, Frederik J.H. Hoogwater, Stefano Partelli, Dominik Wiese, Charlotte Heidsma, Benno Cardini, Eckhard Klieser, Katharina Marsoner, Uwe Fröschl, Sabine Thalhammer, Ines Fischer, Georg Göbel, Andreas Hauer, Tobias Kiesslich, Philipp Ellmerer, Reinhold Klug, Daniel Neureiter, Helwig Wundsam, Franz Sellner, Peter Kornprat, Reinhold Függer, Dietmar Öfner, Elisabeth J.M. Nieveen van Dijkum, Detlef K. Bartsch, Ruben H.J. de Kleine, Massimo Falconi, and Stefan Stättner. 2020. "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" Cancers 12, no. 5: 1235. https://doi.org/10.3390/cancers12051235

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