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Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow‐up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantia...

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Autores principales: Strijker, Marin, Soer, Eline C., de Pastena, Matteo, Creemers, Aafke, Balduzzi, Alberto, Beagan, Jamie J., Busch, Olivier R., van Delden, Otto M., Halfwerk, Hans, van Hooft, Jeanin E., van Lienden, Krijn P., Marchegiani, Giovanni, Meijer, Sybren L., van Noesel, Carel J., Reinten, Roy J., Roos, Eva, Schokker, Sandor, Verheij, Joanne, van de Vijver, Marc J., Waasdorp, Cynthia, Wilmink, Johanna W., Ylstra, Bauke, Besselink, Marc G., Bijlsma, Maarten F., Dijk, Frederike, van Laarhoven, Hanneke W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004068/
https://www.ncbi.nlm.nih.gov/pubmed/31340061
http://dx.doi.org/10.1002/ijc.32586
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author Strijker, Marin
Soer, Eline C.
de Pastena, Matteo
Creemers, Aafke
Balduzzi, Alberto
Beagan, Jamie J.
Busch, Olivier R.
van Delden, Otto M.
Halfwerk, Hans
van Hooft, Jeanin E.
van Lienden, Krijn P.
Marchegiani, Giovanni
Meijer, Sybren L.
van Noesel, Carel J.
Reinten, Roy J.
Roos, Eva
Schokker, Sandor
Verheij, Joanne
van de Vijver, Marc J.
Waasdorp, Cynthia
Wilmink, Johanna W.
Ylstra, Bauke
Besselink, Marc G.
Bijlsma, Maarten F.
Dijk, Frederike
van Laarhoven, Hanneke W.
author_facet Strijker, Marin
Soer, Eline C.
de Pastena, Matteo
Creemers, Aafke
Balduzzi, Alberto
Beagan, Jamie J.
Busch, Olivier R.
van Delden, Otto M.
Halfwerk, Hans
van Hooft, Jeanin E.
van Lienden, Krijn P.
Marchegiani, Giovanni
Meijer, Sybren L.
van Noesel, Carel J.
Reinten, Roy J.
Roos, Eva
Schokker, Sandor
Verheij, Joanne
van de Vijver, Marc J.
Waasdorp, Cynthia
Wilmink, Johanna W.
Ylstra, Bauke
Besselink, Marc G.
Bijlsma, Maarten F.
Dijk, Frederike
van Laarhoven, Hanneke W.
author_sort Strijker, Marin
collection PubMed
description Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow‐up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell‐free DNA from plasma samples of 58 treatment‐naive mPDAC patients was isolated and sequenced using a custom‐made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross‐check with droplet digital PCR showed good agreement in Bland–Altman analysis (p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval [CI] 1.6–4.9) versus 8.4 (95% CI 1.6–15.1) months in patients with detectable versus undetectable ctDNA (p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio [HR] 1.05, 95% CI 1.01–1.09, p = 0.005; HR 1.00, 95% CI 1.01–1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS.
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spelling pubmed-70040682020-02-11 Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma Strijker, Marin Soer, Eline C. de Pastena, Matteo Creemers, Aafke Balduzzi, Alberto Beagan, Jamie J. Busch, Olivier R. van Delden, Otto M. Halfwerk, Hans van Hooft, Jeanin E. van Lienden, Krijn P. Marchegiani, Giovanni Meijer, Sybren L. van Noesel, Carel J. Reinten, Roy J. Roos, Eva Schokker, Sandor Verheij, Joanne van de Vijver, Marc J. Waasdorp, Cynthia Wilmink, Johanna W. Ylstra, Bauke Besselink, Marc G. Bijlsma, Maarten F. Dijk, Frederike van Laarhoven, Hanneke W. Int J Cancer Tumor Markers and Signatures Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow‐up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell‐free DNA from plasma samples of 58 treatment‐naive mPDAC patients was isolated and sequenced using a custom‐made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross‐check with droplet digital PCR showed good agreement in Bland–Altman analysis (p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval [CI] 1.6–4.9) versus 8.4 (95% CI 1.6–15.1) months in patients with detectable versus undetectable ctDNA (p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio [HR] 1.05, 95% CI 1.01–1.09, p = 0.005; HR 1.00, 95% CI 1.01–1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS. John Wiley & Sons, Inc. 2019-08-13 2020-03-01 /pmc/articles/PMC7004068/ /pubmed/31340061 http://dx.doi.org/10.1002/ijc.32586 Text en © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Tumor Markers and Signatures
Strijker, Marin
Soer, Eline C.
de Pastena, Matteo
Creemers, Aafke
Balduzzi, Alberto
Beagan, Jamie J.
Busch, Olivier R.
van Delden, Otto M.
Halfwerk, Hans
van Hooft, Jeanin E.
van Lienden, Krijn P.
Marchegiani, Giovanni
Meijer, Sybren L.
van Noesel, Carel J.
Reinten, Roy J.
Roos, Eva
Schokker, Sandor
Verheij, Joanne
van de Vijver, Marc J.
Waasdorp, Cynthia
Wilmink, Johanna W.
Ylstra, Bauke
Besselink, Marc G.
Bijlsma, Maarten F.
Dijk, Frederike
van Laarhoven, Hanneke W.
Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
title Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
title_full Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
title_fullStr Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
title_full_unstemmed Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
title_short Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
title_sort circulating tumor dna quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma
topic Tumor Markers and Signatures
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004068/
https://www.ncbi.nlm.nih.gov/pubmed/31340061
http://dx.doi.org/10.1002/ijc.32586
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