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Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) may be curative for colorectal cancer patients with peritoneal metastases (PMs) but it has a high rate of morbidity. Accurate preoperative patient selection is therefore imperative, but is constrained by the limitations...

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Autores principales: Beagan, Jamie J., Sluiter, Nina R., Bach, Sander, Eijk, Paul P., Vlek, Stijn L., Heideman, Daniëlle A. M., Kusters, Miranda, Pegtel, D. Michiel, Kazemier, Geert, van Grieken, Nicole C. T., Ylstra, Bauke, Tuynman, Jurriaan B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357031/
https://www.ncbi.nlm.nih.gov/pubmed/32512811
http://dx.doi.org/10.3390/jcm9061738
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author Beagan, Jamie J.
Sluiter, Nina R.
Bach, Sander
Eijk, Paul P.
Vlek, Stijn L.
Heideman, Daniëlle A. M.
Kusters, Miranda
Pegtel, D. Michiel
Kazemier, Geert
van Grieken, Nicole C. T.
Ylstra, Bauke
Tuynman, Jurriaan B.
author_facet Beagan, Jamie J.
Sluiter, Nina R.
Bach, Sander
Eijk, Paul P.
Vlek, Stijn L.
Heideman, Daniëlle A. M.
Kusters, Miranda
Pegtel, D. Michiel
Kazemier, Geert
van Grieken, Nicole C. T.
Ylstra, Bauke
Tuynman, Jurriaan B.
author_sort Beagan, Jamie J.
collection PubMed
description Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) may be curative for colorectal cancer patients with peritoneal metastases (PMs) but it has a high rate of morbidity. Accurate preoperative patient selection is therefore imperative, but is constrained by the limitations of current imaging techniques. In this pilot study, we explored the feasibility of circulating tumor (ct) DNA analysis to select patients for CRS-HIPEC. Thirty patients eligible for CRS-HIPEC provided blood samples preoperatively and during follow-up if the procedure was completed. Targeted Next-Generation Sequencing (NGS) of DNA from PMs was used to identify bespoke mutations that were subsequently tested in corresponding plasma cell-free (cf) DNA samples using droplet digital (dd) PCR. CtDNA was detected preoperatively in cfDNA samples from 33% of patients and was associated with a reduced disease-free survival (DFS) after CRS-HIPEC (median 6.0 months vs median not reached, p = 0.016). This association could indicate the presence of undiagnosed systemic metastases or an increased metastatic potential of the tumors. We demonstrate the feasibility of ctDNA to serve as a preoperative marker of recurrence in patients with PMs of colorectal cancer using a highly sensitive technique. A more appropriate treatment for patients with preoperative ctDNA detection may be systemic chemotherapy in addition to, or instead of, CRS-HIPEC.
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spelling pubmed-73570312020-07-23 Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study Beagan, Jamie J. Sluiter, Nina R. Bach, Sander Eijk, Paul P. Vlek, Stijn L. Heideman, Daniëlle A. M. Kusters, Miranda Pegtel, D. Michiel Kazemier, Geert van Grieken, Nicole C. T. Ylstra, Bauke Tuynman, Jurriaan B. J Clin Med Article Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) may be curative for colorectal cancer patients with peritoneal metastases (PMs) but it has a high rate of morbidity. Accurate preoperative patient selection is therefore imperative, but is constrained by the limitations of current imaging techniques. In this pilot study, we explored the feasibility of circulating tumor (ct) DNA analysis to select patients for CRS-HIPEC. Thirty patients eligible for CRS-HIPEC provided blood samples preoperatively and during follow-up if the procedure was completed. Targeted Next-Generation Sequencing (NGS) of DNA from PMs was used to identify bespoke mutations that were subsequently tested in corresponding plasma cell-free (cf) DNA samples using droplet digital (dd) PCR. CtDNA was detected preoperatively in cfDNA samples from 33% of patients and was associated with a reduced disease-free survival (DFS) after CRS-HIPEC (median 6.0 months vs median not reached, p = 0.016). This association could indicate the presence of undiagnosed systemic metastases or an increased metastatic potential of the tumors. We demonstrate the feasibility of ctDNA to serve as a preoperative marker of recurrence in patients with PMs of colorectal cancer using a highly sensitive technique. A more appropriate treatment for patients with preoperative ctDNA detection may be systemic chemotherapy in addition to, or instead of, CRS-HIPEC. MDPI 2020-06-04 /pmc/articles/PMC7357031/ /pubmed/32512811 http://dx.doi.org/10.3390/jcm9061738 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Beagan, Jamie J.
Sluiter, Nina R.
Bach, Sander
Eijk, Paul P.
Vlek, Stijn L.
Heideman, Daniëlle A. M.
Kusters, Miranda
Pegtel, D. Michiel
Kazemier, Geert
van Grieken, Nicole C. T.
Ylstra, Bauke
Tuynman, Jurriaan B.
Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study
title Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study
title_full Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study
title_fullStr Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study
title_full_unstemmed Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study
title_short Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study
title_sort circulating tumor dna as a preoperative marker of recurrence in patients with peritoneal metastases of colorectal cancer: a clinical feasibility study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357031/
https://www.ncbi.nlm.nih.gov/pubmed/32512811
http://dx.doi.org/10.3390/jcm9061738
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