2021年9月15日
Clinical impact of detecting low-frequency variants in cell-free DNA on treatment of castration-resistant prostate cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research
- 巻
- 27
- 号
- 22
- 開始ページ
- 6164
- 終了ページ
- 6173
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1158/1078-0432.CCR-21-2328
PURPOSE: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from CRPC patients and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. EXPERIMENTAL DESIGN: This prospective, multicenter cohort study enrolled CRPC patients eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pre-treatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF {greater than or equal to} 0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. RESULTS: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.24-5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60-8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. CONCLUSIONS: Detecting low-frequency ctDNA variants with a VAF < 1% is important to identify clinically informative genomic alterations in CRPC.
- リンク情報
- ID情報
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- DOI : 10.1158/1078-0432.CCR-21-2328
- PubMed ID : 34526361