TY - JOUR
T1 - Diagnostic accuracy and added value of blood-based protein biomarkers for pancreatic cancer
T2 - A meta-analysis of aggregate and individual participant data
AU - Boyd, Lenka N. C.
AU - Ali, Mahsoem
AU - Leeflang, Mariska M. G.
AU - Treglia, Giorgio
AU - de Vries, Ralph
AU - le Large, Tessa Y. S.
AU - Besselink, Marc G.
AU - Giovannetti, Elisa
AU - van Laarhoven, Hanneke W. M.
AU - Kazemier, Geert
N1 - Funding Information: This study was supported by the Bennink Foundation (L.N.C.B., M.A., T.Y.S.L.L.,. E.G., and G.K.). E.G. and G.K. were additionally supported by the Dutch Cancer Foundation (grant # 13598 and grant # 10401 ) and start-up AIRC grant. Publisher Copyright: © 2022 The Author(s)
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background: Novel blood-based protein biomarkers may be of value for efficient, accurate, and non-invasive diagnosis of pancreatic cancer. This study assesses the diagnostic accuracy of newly recognized blood-based protein biomarkers for detecting pancreatic cancer, and investigates their added value to CA19-9, the common blood-based biomarker in clinical use for pancreatic cancer. Methods: PubMed, Embase, Web of Science, and the Wiley/Cochrane Library were systematically searched from inception until June 2022. A meta-analysis of aggregate and individual participant data was conducted using frequentist and Bayesian hierarchical random-effects models. The added clinical utility of protein biomarkers was investigated using bootstrap bias-corrected decision curve analyses. Findings: Aggregate data from 28 primary studies (6127 participants) were included, of which 8 studies (1790 participants) provided individual participant data. CA19-9 was significantly more accurate than MIC-1 for distinguishing pancreatic cancer from benign disease (AUC, 0.83 vs 0.74; relative diagnostic odds ratio [rDOR], 2.10 [95% CI, 0.98–4.48]; p = 0.002), THBS2 (AUC, 0.87 vs 0.69; rDOR, 4.53 [2.16–9.39]; p < 0.0001), TIMP-1 (AUC, 0.91 vs 0.70; rDOR, 8.00 [3.81–16.9]; p < 0.0001), OPN (AUC, 0.89 vs 0.74; rDOR, 4.22 [1.13–15.6]; p < 0.0001), ICAM-1 (AUC, 0.91 vs 0.68; rDOR 9.30 [0.87–99.5]; p < 0.0001), and IGFBP2 (AUC, 0.91 vs 0.68; rDOR, 4.48 [0.78–24.3]; p < 0.0001). The addition of these novel protein biomarkers to CA19-9 did not significantly improve the AUC, and resulted in minor increases or limited decreases in clinical utility. Interpretation: Novel protein biomarkers have moderate diagnostic accuracy, do not outperform CA19-9 in differentiating pancreatic cancer from benign disease, and show limited added clinical value to CA19-9. We propose recommendations to aid the development of minimally invasive diagnostic tests with sufficient clinical utility to improve the management of patients with suspected pancreatic cancer. Funding: Bennink Foundation, Dutch Cancer Foundation (KWF Kankerbestrijding), and AIRC.
AB - Background: Novel blood-based protein biomarkers may be of value for efficient, accurate, and non-invasive diagnosis of pancreatic cancer. This study assesses the diagnostic accuracy of newly recognized blood-based protein biomarkers for detecting pancreatic cancer, and investigates their added value to CA19-9, the common blood-based biomarker in clinical use for pancreatic cancer. Methods: PubMed, Embase, Web of Science, and the Wiley/Cochrane Library were systematically searched from inception until June 2022. A meta-analysis of aggregate and individual participant data was conducted using frequentist and Bayesian hierarchical random-effects models. The added clinical utility of protein biomarkers was investigated using bootstrap bias-corrected decision curve analyses. Findings: Aggregate data from 28 primary studies (6127 participants) were included, of which 8 studies (1790 participants) provided individual participant data. CA19-9 was significantly more accurate than MIC-1 for distinguishing pancreatic cancer from benign disease (AUC, 0.83 vs 0.74; relative diagnostic odds ratio [rDOR], 2.10 [95% CI, 0.98–4.48]; p = 0.002), THBS2 (AUC, 0.87 vs 0.69; rDOR, 4.53 [2.16–9.39]; p < 0.0001), TIMP-1 (AUC, 0.91 vs 0.70; rDOR, 8.00 [3.81–16.9]; p < 0.0001), OPN (AUC, 0.89 vs 0.74; rDOR, 4.22 [1.13–15.6]; p < 0.0001), ICAM-1 (AUC, 0.91 vs 0.68; rDOR 9.30 [0.87–99.5]; p < 0.0001), and IGFBP2 (AUC, 0.91 vs 0.68; rDOR, 4.48 [0.78–24.3]; p < 0.0001). The addition of these novel protein biomarkers to CA19-9 did not significantly improve the AUC, and resulted in minor increases or limited decreases in clinical utility. Interpretation: Novel protein biomarkers have moderate diagnostic accuracy, do not outperform CA19-9 in differentiating pancreatic cancer from benign disease, and show limited added clinical value to CA19-9. We propose recommendations to aid the development of minimally invasive diagnostic tests with sufficient clinical utility to improve the management of patients with suspected pancreatic cancer. Funding: Bennink Foundation, Dutch Cancer Foundation (KWF Kankerbestrijding), and AIRC.
UR - http://www.scopus.com/inward/record.url?scp=85142422951&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.eclinm.2022.101747
DO - https://doi.org/10.1016/j.eclinm.2022.101747
M3 - Article
C2 - 36457649
SN - 2589-5370
VL - 55
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 101747
ER -