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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Published in:International journal of cancer 2023-04, Vol.152 (7), p.1444-1451
Main Authors: 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
Format: Article
Language:English
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
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Summary: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 
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.34392