TY - JOUR
T1 - Clinical value of ctDNA in upper-GI cancers
T2 - A systematic review and meta-analysis
AU - Creemers, A.
AU - Krausz, S.
AU - Strijker, M.
AU - van der Wel, M. J.
AU - Soer, E. C.
AU - Reinten, R. J.
AU - Besselink, M. G.
AU - Wilmink, J. W.
AU - van de Vijver, M. J.
AU - van Noesel, C. J.M.
AU - Verheij, J.
AU - Meijer, S. L.
AU - Dijk, F.
AU - Bijlsma, M. F.
AU - van Oijen, M. G.H.
AU - van Laarhoven, H. W.M.
N1 - Funding Information: Dr. S. Krausz received research funding from Nijbakker Morra Foundation . Dr. Maarten F. Bijlsma received research funding from Celgene . Dr. Martijn G. H. van Oijen received unrestricted research grants from Bayer , Lilly , Merck Serono , and Roche . Prof. dr. Hanneke W. M. van Laarhoven has served as a consultant for Celgene , Lilly , Nordic , and Philips , and has received unrestricted research funding from Bayer , Celgene , Lilly , Merck Serono , MSD , Nordic , Philips and Roche . None of these parties were involved in drafting this review. Publisher Copyright: © 2017 Elsevier B.V.
PY - 2017/12
Y1 - 2017/12
N2 - Background The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract. Methods PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017. The diagnostic accuracy and, using random-effect pair-wise meta-analyses, the prognostic value of ctDNA was assessed. Results A total of 34 studies met the inclusion criteria. For esophageal and gastric cancer, amplification of oncogenes in blood, such as HER2 and MYC, can be relevant for diagnostic purposes, and to predict treatment response in certain patient subpopulations. Given the limited number of studies assessing the role of ctDNA in esophageal and gastric cancer, the meta-analysis estimated the diagnostic accuracy and predictive value of ctDNA in pancreatic cancer only (n = 10). The pooled sensitivity and specificity of ctDNA as a diagnostic tool in pancreatic cancer were 28% and 95%, respectively. Patients with pancreatic cancer and detectable ctDNA demonstrated a worse overall survival compared to patients with undetectable ctDNA (HR 1.92, 95% confidence interval (CI) 1.15–3.22, p = 0.01). Conclusion The presence of ctDNA is significantly associated with a poor prognosis in patients with pancreatic cancer. The use of ctDNA in clinical practice is promising, although standardization of sequencing techniques and further development of high-sensitive detection methods is needed.
AB - Background The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract. Methods PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017. The diagnostic accuracy and, using random-effect pair-wise meta-analyses, the prognostic value of ctDNA was assessed. Results A total of 34 studies met the inclusion criteria. For esophageal and gastric cancer, amplification of oncogenes in blood, such as HER2 and MYC, can be relevant for diagnostic purposes, and to predict treatment response in certain patient subpopulations. Given the limited number of studies assessing the role of ctDNA in esophageal and gastric cancer, the meta-analysis estimated the diagnostic accuracy and predictive value of ctDNA in pancreatic cancer only (n = 10). The pooled sensitivity and specificity of ctDNA as a diagnostic tool in pancreatic cancer were 28% and 95%, respectively. Patients with pancreatic cancer and detectable ctDNA demonstrated a worse overall survival compared to patients with undetectable ctDNA (HR 1.92, 95% confidence interval (CI) 1.15–3.22, p = 0.01). Conclusion The presence of ctDNA is significantly associated with a poor prognosis in patients with pancreatic cancer. The use of ctDNA in clinical practice is promising, although standardization of sequencing techniques and further development of high-sensitive detection methods is needed.
KW - Circulating tumor DNA
KW - Esophageal
KW - Gastric
KW - Meta-analysis
KW - Pancreatic
UR - http://www.scopus.com/inward/record.url?scp=85027855506&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bbcan.2017.08.002
DO - https://doi.org/10.1016/j.bbcan.2017.08.002
M3 - Review article
C2 - 28801248
SN - 0304-419X
VL - 1868
SP - 394
EP - 403
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 2
ER -