Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial
The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/6/516 |
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| author | François-Clément Bidard Nicolas Kiavue Marc Ychou Luc Cabel Marc-Henri Stern Jordan Madic Adrien Saliou Aurore Rampanou Charles Decraene Olivier Bouché Michel Rivoire François Ghiringhelli Eric Francois Rosine Guimbaud Laurent Mineur Faiza Khemissa-Akouz Thibault Mazard Driffa Moussata Charlotte Proudhon Jean-Yves Pierga Trevor Stanbury Simon Thézenas Pascale Mariani |
| author_facet | François-Clément Bidard Nicolas Kiavue Marc Ychou Luc Cabel Marc-Henri Stern Jordan Madic Adrien Saliou Aurore Rampanou Charles Decraene Olivier Bouché Michel Rivoire François Ghiringhelli Eric Francois Rosine Guimbaud Laurent Mineur Faiza Khemissa-Akouz Thibault Mazard Driffa Moussata Charlotte Proudhon Jean-Yves Pierga Trevor Stanbury Simon Thézenas Pascale Mariani |
| author_sort | François-Clément Bidard |
| collection | DOAJ |
| description | The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch<sup>®</sup>) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (≥3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (<i>p</i> = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (<i>p</i> < 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection. |
| first_indexed | 2024-03-12T07:53:48Z |
| format | Article |
| id | doaj.art-47114e9137bc4e8588861221bc11490c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:53:48Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-47114e9137bc4e8588861221bc11490c2023-09-02T20:26:21ZengMDPI AGCells2073-44092019-05-018651610.3390/cells8060516cells8060516Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 TrialFrançois-Clément Bidard0Nicolas Kiavue1Marc Ychou2Luc Cabel3Marc-Henri Stern4Jordan Madic5Adrien Saliou6Aurore Rampanou7Charles Decraene8Olivier Bouché9Michel Rivoire10François Ghiringhelli11Eric Francois12Rosine Guimbaud13Laurent Mineur14Faiza Khemissa-Akouz15Thibault Mazard16Driffa Moussata17Charlotte Proudhon18Jean-Yves Pierga19Trevor Stanbury20Simon Thézenas21Pascale Mariani22Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, FranceDepartment of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, FranceDepartment of Digestive Oncology, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, FranceDepartment of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, FranceINSERM U830, Institut Curie, PSL Research University, 75005 Paris, FranceCirculating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, FranceCirculating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, FranceCirculating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, FranceCirculating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, FranceDepartment of Medical Oncology, Hôpital Robert Debré, Reims University Hospital, 51100 Reims, FranceDepartment of Digestive Oncology, Centre Léon Bérard, 69008 Lyon, FranceINSERM U866, Centre Georges-François Leclerc, 21000 Dijon, FranceDepartment of Medical Oncology, Centre Antoine Lacassagne, 06189 Nice, FranceDepartment of Digestive Oncology, CHU de Toulouse, 31059 Toulouse, FranceDepartment of Digestive Oncology, Institut Sainte Catherine, 84000 Avignon, FranceDepartment of Gastroenterology, Hôpital Saint Jean, 66000 Perpignan, FranceDepartment of Digestive Oncology, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, FranceDepartment of Gastroenterology, CHRU de Tours, 37044 Tours, FranceCirculating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, 75005 Paris, FranceDepartment of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, FranceUCGI Group, R&D UNICANCER, 75654 Paris, FranceBiometrics Unit, ICM Regional Cancer Institute of Montpellier, 34298 Montpellier, FranceDepartment of Surgical Oncology, Institut Curie, PSL Research University, 75005 Paris, FranceThe management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch<sup>®</sup>) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (≥3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (<i>p</i> = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (<i>p</i> < 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.https://www.mdpi.com/2073-4409/8/6/516circulating tumor cellscirculating tumor DNAliquid biopsymetastatic colorectal cancerFOLFIRINOX |
| spellingShingle | François-Clément Bidard Nicolas Kiavue Marc Ychou Luc Cabel Marc-Henri Stern Jordan Madic Adrien Saliou Aurore Rampanou Charles Decraene Olivier Bouché Michel Rivoire François Ghiringhelli Eric Francois Rosine Guimbaud Laurent Mineur Faiza Khemissa-Akouz Thibault Mazard Driffa Moussata Charlotte Proudhon Jean-Yves Pierga Trevor Stanbury Simon Thézenas Pascale Mariani Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial Cells circulating tumor cells circulating tumor DNA liquid biopsy metastatic colorectal cancer FOLFIRINOX |
| title | Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial |
| title_full | Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial |
| title_fullStr | Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial |
| title_full_unstemmed | Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial |
| title_short | Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial |
| title_sort | circulating tumor cells and circulating tumor dna detection in potentially resectable metastatic colorectal cancer a prospective ancillary study to the unicancer prodige 14 trial |
| topic | circulating tumor cells circulating tumor DNA liquid biopsy metastatic colorectal cancer FOLFIRINOX |
| url | https://www.mdpi.com/2073-4409/8/6/516 |
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