A Creemers1, S Krausz2, M Strijker3, M J van der Wel4, E C Soer4, R J Reinten4, M G Besselink3, J W Wilmink2, M J van de Vijver4, C J M van Noesel4, J Verheij4, S L Meijer4, F Dijk4, M F Bijlsma5, M G H van Oijen2, H W M van Laarhoven6. 1. Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands; Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. Electronic address: a.creemers@amc.uva.nl. 2. Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. 3. Department of Surgery, AMC, The Netherlands. 4. Department of Pathology, AMC, The Netherlands. 5. Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands. 6. Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands; Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands.
Abstract
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.
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.
Authors: Vincent P Groot; Georgios Gemenetzis; Alex B Blair; Roberto J Rivero-Soto; Jun Yu; Ammar A Javed; Richard A Burkhart; Inne H M Borel Rinkes; I Quintus Molenaar; John L Cameron; Matthew J Weiss; Christopher L Wolfgang; Jin He Journal: Ann Surg Date: 2018-03-23 Impact factor: 12.969
Authors: William J Chapin; Jacob E Till; Wei-Ting Hwang; Jennifer R Eads; Thomas B Karasic; Peter J O'Dwyer; Charles J Schneider; Ursina R Teitelbaum; Janae Romeo; Taylor A Black; Theresa E Christensen; Colleen Redlinger Tabery; Amanda Anderson; Megan Slade; Michael LaRiviere; Stephanie S Yee; Kim A Reiss; Mark H O'Hara; Erica L Carpenter Journal: JCO Precis Oncol Date: 2022-07
Authors: Tej D Azad; Aadel A Chaudhuri; Penny Fang; Yawei Qiao; Mohammad S Esfahani; Jacob J Chabon; Emily G Hamilton; Yi D Yang; Alex Lovejoy; Aaron M Newman; David M Kurtz; Michael Jin; Joseph Schroers-Martin; Henning Stehr; Chih Long Liu; Angela Bik-Yu Hui; Viren Patel; Dipen Maru; Steven H Lin; Ash A Alizadeh; Maximilian Diehn Journal: Gastroenterology Date: 2019-11-09 Impact factor: 22.682
Authors: Berend Jan van der Wilk; Ben M Eyck; Manon C W Spaander; Roelf Valkema; Sjoerd M Lagarde; Bas P L Wijnhoven; J Jan B van Lanschot Journal: Dig Surg Date: 2018-09-18 Impact factor: 2.588
Authors: Vincent P Groot; Georgios Gemenetzis; Alex B Blair; Roberto J Rivero-Soto; Jun Yu; Ammar A Javed; Richard A Burkhart; Inne H M Borel Rinkes; I Quintus Molenaar; John L Cameron; Matthew J Weiss; Christopher L Wolfgang; Jin He Journal: Ann Surg Date: 2019-06 Impact factor: 13.787
Authors: Vincent P Groot; Stacy Mosier; Ammar A Javed; Jonathan A Teinor; Georgios Gemenetzis; Ding Ding; Lisa M Haley; Jun Yu; Richard A Burkhart; Alina Hasanain; Marija Debeljak; Hirohiko Kamiyama; Amol Narang; Daniel A Laheru; Lei Zheng; Ming-Tseh Lin; Christopher D Gocke; Elliot K Fishman; Ralph H Hruban; Michael G Goggins; I Quintus Molenaar; John L Cameron; Matthew J Weiss; Victor E Velculescu; Jin He; Christopher L Wolfgang; James R Eshleman Journal: Clin Cancer Res Date: 2019-05-29 Impact factor: 13.801