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Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients
The detection of RAS mutations and co-mutations in liquid biopsy offers a novel paradigm for the dynamic management of metastatic colorectal cancer (mCRC) patients. Expanding the results of the prospective OMITERC (OMIcs application from solid to liquid biopsy for a personalized ThERapy of Cancer) p...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663919/ https://www.ncbi.nlm.nih.gov/pubmed/38027900 http://dx.doi.org/10.1016/j.heliyon.2023.e21853 |
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author | Lavacchi, Daniele Gelmini, Stefania Calabri, Adele Rossi, Gemma Simi, Lisa Caliman, Enrico Mancini, Irene Salvianti, Francesca Petroni, Giulia Guidolin, Alessia Scolari, Federico Messerini, Luca Pillozzi, Serena Pinzani, Pamela Antonuzzo, Lorenzo |
author_facet | Lavacchi, Daniele Gelmini, Stefania Calabri, Adele Rossi, Gemma Simi, Lisa Caliman, Enrico Mancini, Irene Salvianti, Francesca Petroni, Giulia Guidolin, Alessia Scolari, Federico Messerini, Luca Pillozzi, Serena Pinzani, Pamela Antonuzzo, Lorenzo |
author_sort | Lavacchi, Daniele |
collection | PubMed |
description | The detection of RAS mutations and co-mutations in liquid biopsy offers a novel paradigm for the dynamic management of metastatic colorectal cancer (mCRC) patients. Expanding the results of the prospective OMITERC (OMIcs application from solid to liquid biopsy for a personalized ThERapy of Cancer) project, we collected blood samples at specific time points from patients who received a first-line chemotherapy (CT) for KRAS-mutated mCRC. CTC quantification was performed by CellSearch® system. Libraries from cfDNA were prepared using the Oncomine™ Colon cfDNA Assay to detect tumour-derived DNA in cfDNA. The analysis involved >240 hotspots in 14 genes. Twenty patients with KRAS-mutated mCRC treated at the Medical Oncology Unit of Careggi University Hospital were prospectively enrolled. Nine patients had available data for longitudinal monitoring of cfDNA. After 6 weeks of first-line CT an increase of KRAS-mutated clone was reported in the only patient who did not obtain disease control, while all patients with decrease of KRAS clones obtained disease control. Overall, in patients with a short (<9 months) progression-free survival (PFS) we registered, at 6 weeks, an increase in cfDNA levels and in KRAS mutations or other co-mutations, i.e. PIK3CA, FBXW7, GNAS, and TP53. In selected cases, co-mutations were able to better anticipate radiological progressive disease (PD) than the increase of KRAS-mutated clones. In conclusion, our study confirms plasma ctDNA as a crucial tool for anticipating PD at an early time point and highlights the value of a comprehensive assessment of clonal dynamics to improve the management of patients with mCRC. |
format | Online Article Text |
id | pubmed-10663919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-106639192023-11-04 Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients Lavacchi, Daniele Gelmini, Stefania Calabri, Adele Rossi, Gemma Simi, Lisa Caliman, Enrico Mancini, Irene Salvianti, Francesca Petroni, Giulia Guidolin, Alessia Scolari, Federico Messerini, Luca Pillozzi, Serena Pinzani, Pamela Antonuzzo, Lorenzo Heliyon Research Article The detection of RAS mutations and co-mutations in liquid biopsy offers a novel paradigm for the dynamic management of metastatic colorectal cancer (mCRC) patients. Expanding the results of the prospective OMITERC (OMIcs application from solid to liquid biopsy for a personalized ThERapy of Cancer) project, we collected blood samples at specific time points from patients who received a first-line chemotherapy (CT) for KRAS-mutated mCRC. CTC quantification was performed by CellSearch® system. Libraries from cfDNA were prepared using the Oncomine™ Colon cfDNA Assay to detect tumour-derived DNA in cfDNA. The analysis involved >240 hotspots in 14 genes. Twenty patients with KRAS-mutated mCRC treated at the Medical Oncology Unit of Careggi University Hospital were prospectively enrolled. Nine patients had available data for longitudinal monitoring of cfDNA. After 6 weeks of first-line CT an increase of KRAS-mutated clone was reported in the only patient who did not obtain disease control, while all patients with decrease of KRAS clones obtained disease control. Overall, in patients with a short (<9 months) progression-free survival (PFS) we registered, at 6 weeks, an increase in cfDNA levels and in KRAS mutations or other co-mutations, i.e. PIK3CA, FBXW7, GNAS, and TP53. In selected cases, co-mutations were able to better anticipate radiological progressive disease (PD) than the increase of KRAS-mutated clones. In conclusion, our study confirms plasma ctDNA as a crucial tool for anticipating PD at an early time point and highlights the value of a comprehensive assessment of clonal dynamics to improve the management of patients with mCRC. Elsevier 2023-11-04 /pmc/articles/PMC10663919/ /pubmed/38027900 http://dx.doi.org/10.1016/j.heliyon.2023.e21853 Text en © 2023 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Lavacchi, Daniele Gelmini, Stefania Calabri, Adele Rossi, Gemma Simi, Lisa Caliman, Enrico Mancini, Irene Salvianti, Francesca Petroni, Giulia Guidolin, Alessia Scolari, Federico Messerini, Luca Pillozzi, Serena Pinzani, Pamela Antonuzzo, Lorenzo Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients |
title | Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients |
title_full | Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients |
title_fullStr | Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients |
title_full_unstemmed | Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients |
title_short | Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients |
title_sort | early changes in circulating tumor dna (ctdna) predict treatment response in metastatic kras-mutated colorectal cancer (mcrc) patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663919/ https://www.ncbi.nlm.nih.gov/pubmed/38027900 http://dx.doi.org/10.1016/j.heliyon.2023.e21853 |
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