期刊
MOLECULAR ONCOLOGY
卷 16, 期 10, 页码 2086-2097出版社
WILEY
DOI: 10.1002/1878-0261.13196
关键词
advanced urothelial carcinoma; biomarker; chromosomal instability; ctDNA; liquid biopsies; pembrolizumab
类别
资金
- Hartwig Medical Foundation
- Stichting Stelvio for Life
This study investigated the use of a gene testing method called mFast-SeqS to evaluate treatment response in patients with mUC. The results showed that the mFast-SeqS score correlated significantly with tissue-based scores and ctDNA levels in the plasma, and a high score was independently associated with lack of clinical benefit from pembrolizumab treatment.
Second-line treatment with immune checkpoint inhibition in patients with metastatic urothelial cancer (mUC) has a low success rate (similar to 20%). Circulating tumour-derived DNA (ctDNA) levels may guide patient stratification, provided that an affordable and robust assay is available. Here, we investigate whether the modified fast aneuploidy screening test-sequencing system (mFast-SeqS) may provide such an assay. To this end, mFast-SeqS was performed on cell-free DNA (cfDNA) from 74 patients with mUC prior to treatment with pembrolizumab. Results were associated with corresponding tissue-based profiles, plasma-based variant allele frequencies (VAFs) and clinical response. We found that plasma-derived mFast-SeqS-based aneuploidy scores significantly correlated with those observed in the corresponding tumour tissue as well as with the ctDNA level in the plasma. in multivariate logistic regression analysis, a high aneuploidy score was independently associated with lack of clinical benefit from treatment with pembrolizumab. In conclusion, mFast-SeqS provides a patient-friendly, high-throughput and affordable method to estimate ctDNA level. Following independent validation, this test could be used to stratify mUC patients for response prior to the initiation of treatment with pembrolizumab.
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