期刊
MOLECULAR ONCOLOGY
卷 14, 期 8, 页码 1670-1679出版社
WILEY
DOI: 10.1002/1878-0261.12729
关键词
bladder cancer; cell-free DNA; circulating tumor DNA; colorectal cancer; trauma
类别
资金
- Danish Council for Independent Research [4183-00619, 7016-00369B]
- Danish Council for Strategic Research [1309-00006B]
- Novo Nordisk Foundation [NNF14OC0012747, NNF17OC0025052, NNF17OC0024464]
- Danish Cancer Society [R107-A7035, R133-A8520-00-S41, R146-A9466-16-S2, R124-A7508]
- Dansk Kraeftforskningsfond [FID1839672]
Detection of circulating tumor DNA (ctDNA) post-treatment is an emerging marker of residual disease. ctDNA constitutes only a minor fraction of the cell-free DNA (cfDNA) circulating in cancer patients, complicating ctDNA detection. This is exacerbated by trauma-induced cfDNA. To guide optimal blood sample timing, we investigated the duration and magnitude of surgical trauma-induced cfDNA in patients with colorectal or bladder cancer. DNA levels were quantified in paired plasma samples collected before and up to 6 weeks after surgery from 436 patients with colorectal cancer and 47 patients with muscle-invasive bladder cancer. To assess whether trauma-induced cfDNA fragments are longer than ordinary cfDNA fragments, the concentration of short (< 1 kb) and long (> 1 kb) fragments was determined for 91 patients. Previously reported ctDNA data from 91 patients with colorectal cancer and 47 patients with bladder cancer were used to assess how trauma-induced DNA affects ctDNA detection. The total cfDNA level increased postoperatively-both in patients with colorectal cancer (mean threefold) and bladder cancer (mean eightfold). The DNA levels were significantly increased up to 4 weeks after surgery in both patient cohorts (P = 0.0005 andP <= 0.0001). The concentration of short, but not long, cfDNA fragments increased postoperatively. Of 25 patients with radiological relapse, eight were ctDNA-positive and 17 were ctDNA-negative in the period with trauma-induced DNA. Analysis of longitudinal samples revealed that five of the negative patients became positive shortly after the release of trauma-induced cfDNA had ceased. In conclusion, surgery was associated with elevated cfDNA levels, persisting up to 4 weeks, which may have masked ctDNA in relapse patients. Trauma-induced cfDNA was of similar size to ordinary cfDNA. To mitigate the impact of trauma-induced cfDNA on ctDNA detection, it is recommended that a second blood sample collected after week 4 is analyzed for patients initially ctDNA negative.
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