Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases
Background: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the associatio...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-08-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421002917 |
| _version_ | 1818651485416718336 |
|---|---|
| author | Karen Bolhuis Iris van 't Erve Clinton Mijnals Pien M. Delis – Van Diemen Joost Huiskens Aysun Komurcu Marta Lopez-Yurda Daan van den Broek Rutger-Jan Swijnenburg Gerrit A. Meijer Cornelis J.A. Punt Remond J.A. Fijneman |
| author_facet | Karen Bolhuis Iris van 't Erve Clinton Mijnals Pien M. Delis – Van Diemen Joost Huiskens Aysun Komurcu Marta Lopez-Yurda Daan van den Broek Rutger-Jan Swijnenburg Gerrit A. Meijer Cornelis J.A. Punt Remond J.A. Fijneman |
| author_sort | Karen Bolhuis |
| collection | DOAJ |
| description | Background: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS). Methods: Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system. Findings: With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p < 0.001). In univariable Cox regression analyses both postoperative detectable ctDNA (HR = 3.3, 95%CI = 1.1–9.6, p = 0.03) and pathologic non-response (HR = 4.6, 95%CI = 1.4–15, p = 0.01) were associated with poorer RFS and were strongly correlated (r = 0.88, p < 0.001). After adjusting for clinical characteristics in pairwise multivariable analyses, postoperative ctDNA status remained associated with RFS. Interpretation: The detection of postoperative ctDNA after secondary resection of CRLM is a promising prognostic factor for RFS and appeared to be highly correlated with pathologic response. |
| first_indexed | 2024-12-17T02:06:52Z |
| format | Article |
| id | doaj.art-ac3dfdb0ce244b71940b89028a6d2ade |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-17T02:06:52Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-ac3dfdb0ce244b71940b89028a6d2ade2022-12-21T22:07:40ZengElsevierEBioMedicine2352-39642021-08-0170103498Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastasesKaren Bolhuis0Iris van 't Erve1Clinton Mijnals2Pien M. Delis – Van Diemen3Joost Huiskens4Aysun Komurcu5Marta Lopez-Yurda6Daan van den Broek7Rutger-Jan Swijnenburg8Gerrit A. Meijer9Cornelis J.A. Punt10Remond J.A. Fijneman11Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, the NetherlandsDepartment of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the NetherlandsDepartment of Pathology, Amphia hospital, Breda, the NetherlandsDepartment of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the NetherlandsSAS Institute B.V., Huizen, the NetherlandsNetherlands Comprehensive Cancer Center, Utrecht, the NetherlandsBiometrics Department, The Netherlands Cancer Institute, Amsterdam, the NetherlandsDepartment of Clinical Chemistry, The Netherlands Cancer Institute, Amsterdam, the NetherlandsDepartment of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, the NetherlandsDepartment of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, the Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Utrecht, the NetherlandsDepartment of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the Netherlands; Corresponding author.Background: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS). Methods: Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system. Findings: With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p < 0.001). In univariable Cox regression analyses both postoperative detectable ctDNA (HR = 3.3, 95%CI = 1.1–9.6, p = 0.03) and pathologic non-response (HR = 4.6, 95%CI = 1.4–15, p = 0.01) were associated with poorer RFS and were strongly correlated (r = 0.88, p < 0.001). After adjusting for clinical characteristics in pairwise multivariable analyses, postoperative ctDNA status remained associated with RFS. Interpretation: The detection of postoperative ctDNA after secondary resection of CRLM is a promising prognostic factor for RFS and appeared to be highly correlated with pathologic response.http://www.sciencedirect.com/science/article/pii/S2352396421002917Colorectal cancerLiver metastasesCirculating tumour DNAResectionRecurrences |
| spellingShingle | Karen Bolhuis Iris van 't Erve Clinton Mijnals Pien M. Delis – Van Diemen Joost Huiskens Aysun Komurcu Marta Lopez-Yurda Daan van den Broek Rutger-Jan Swijnenburg Gerrit A. Meijer Cornelis J.A. Punt Remond J.A. Fijneman Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases EBioMedicine Colorectal cancer Liver metastases Circulating tumour DNA Resection Recurrences |
| title | Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases |
| title_full | Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases |
| title_fullStr | Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases |
| title_full_unstemmed | Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases |
| title_short | Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases |
| title_sort | postoperative circulating tumour dna is associated with pathologic response and recurrence free survival after resection of colorectal cancer liver metastases |
| topic | Colorectal cancer Liver metastases Circulating tumour DNA Resection Recurrences |
| url | http://www.sciencedirect.com/science/article/pii/S2352396421002917 |
| work_keys_str_mv | AT karenbolhuis postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT irisvanterve postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT clintonmijnals postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT pienmdelisvandiemen postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT joosthuiskens postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT aysunkomurcu postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT martalopezyurda postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT daanvandenbroek postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT rutgerjanswijnenburg postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT gerritameijer postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT cornelisjapunt postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases AT remondjafijneman postoperativecirculatingtumourdnaisassociatedwithpathologicresponseandrecurrencefreesurvivalafterresectionofcolorectalcancerlivermetastases |