A universal cell‐free DNA approach for response prediction to preoperative chemoradiation in rectal cancer

The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ‐preservation strategies. However, better tools are sti...

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Veröffentlicht in:International journal of cancer 2023-04, Vol.152 (7), p.1444-1451
Hauptverfasser: Grinshpun, Albert, Kustanovich, Anatoli, Neiman, Daniel, Lehmann‐Werman, Roni, Zick, Aviad, Meir, Karen, Vainer, Elez, Granit, Roy Z., Arad, Amit, Daskal, Noa, Schwartz, Ruth, Sapir, Eli, Maoz, Myriam, Tahover, Esther, Moss, Joshua, Ben‐Dov, Iddo Z., Peretz, Tamar, Hubert, Ayala, Shemer, Ruth, Dor, Yuval
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container_issue 7
container_start_page 1444
container_title International journal of cancer
container_volume 152
creator Grinshpun, Albert
Kustanovich, Anatoli
Neiman, Daniel
Lehmann‐Werman, Roni
Zick, Aviad
Meir, Karen
Vainer, Elez
Granit, Roy Z.
Arad, Amit
Daskal, Noa
Schwartz, Ruth
Sapir, Eli
Maoz, Myriam
Tahover, Esther
Moss, Joshua
Ben‐Dov, Iddo Z.
Peretz, Tamar
Hubert, Ayala
Shemer, Ruth
Dor, Yuval
description The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ‐preservation strategies. However, better tools are still needed to personalize therapy for the individual patient. In this prospective observational study, we analyzed colon‐derived cell‐free (cf)DNA (c‐cfDNA) using a tissue‐specific DNA methylation signature, and its association with therapy outcomes. Analyzing plasma samples (n = 303) collected during nCRT from 37 patients with locally advanced rectal cancer (LARC), we identified colon‐specific methylation markers that discriminated healthy individuals from patients with untreated LARC (area under the curve, 0.81; 95% confidence interval, 0.70‐0.92; P 
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In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ‐preservation strategies. However, better tools are still needed to personalize therapy for the individual patient. In this prospective observational study, we analyzed colon‐derived cell‐free (cf)DNA (c‐cfDNA) using a tissue‐specific DNA methylation signature, and its association with therapy outcomes. Analyzing plasma samples (n = 303) collected during nCRT from 37 patients with locally advanced rectal cancer (LARC), we identified colon‐specific methylation markers that discriminated healthy individuals from patients with untreated LARC (area under the curve, 0.81; 95% confidence interval, 0.70‐0.92; P &lt; .0001). Baseline c‐cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c‐cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c‐cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/ml, respectively; P = .013). Increased c‐cfDNA after 1 week of therapy was also associated with disease recurrence. Methylation‐based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de‐escalation strategies. What's new? The treatment of locally advanced rectal cancer is a rapidly evolving field, involves multidisciplinary decision‐making, and has no predictive biomarkers for optimal treatment selection. Here, we show that cell‐free DNA from colorectal cells can be identified in patients with rectal cancer, using tissue‐specific methylation markers. 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Baseline c‐cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c‐cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c‐cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/ml, respectively; P = .013). Increased c‐cfDNA after 1 week of therapy was also associated with disease recurrence. Methylation‐based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de‐escalation strategies. What's new? The treatment of locally advanced rectal cancer is a rapidly evolving field, involves multidisciplinary decision‐making, and has no predictive biomarkers for optimal treatment selection. Here, we show that cell‐free DNA from colorectal cells can be identified in patients with rectal cancer, using tissue‐specific methylation markers. 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Baseline c‐cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c‐cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c‐cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/ml, respectively; P = .013). Increased c‐cfDNA after 1 week of therapy was also associated with disease recurrence. Methylation‐based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de‐escalation strategies. What's new? The treatment of locally advanced rectal cancer is a rapidly evolving field, involves multidisciplinary decision‐making, and has no predictive biomarkers for optimal treatment selection. Here, we show that cell‐free DNA from colorectal cells can be identified in patients with rectal cancer, using tissue‐specific methylation markers. 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subjects Biopsy
Cancer
Cell-Free Nucleic Acids - genetics
cell‐free DNA
chemoradiation
Chemoradiotherapy
Colon
Colon cancer
Colorectal cancer
DNA methylation
Eradication
Humans
Innovative Tools and Methods
Medical research
methylation
neoadjuvant
Neoadjuvant Therapy
Neoplasm Recurrence, Local
Patients
rectal cancer
Rectal Neoplasms - genetics
Rectal Neoplasms - pathology
Rectal Neoplasms - therapy
Rectum
Rectum - pathology
Retrospective Studies
Treatment Outcome
Tumors
title A universal cell‐free DNA approach for response prediction to preoperative chemoradiation in rectal cancer
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