Clinical Impact of Detecting Low-Frequency Variants in Cell-Free DNA on Treatment of Castration-Resistant Prostate Cancer
| Autor: | Naohiro Fujimoto, Hideyasu Matsuyama, Chikara Ohyama, Hiroko Kimura, Takayuki Sumiyoshi, Satoshi Ishitoya, Takashi Kobayashi, Naoki Terada, Hiroaki Matsumoto, Kei Mizuno, Shingo Hatakeyama, Shintaro Narita, Osamu Ogawa, Masatoshi Eto, Yuki Kamiyama, Hitoshi Yamada, Hiroshi Okuno, Akihiro Ito, Tomonori Habuchi, Takatsugu Okegawa, Hidenori Kanno, Yoshiyuki Matsui, Katsuhiro Ito, Akihiro Fujimoto, Takuro Sunada, Takayuki Goto, Yu Miyazaki, Masaki Shiota, Toshiyuki Kamoto, Hiroyuki Nishiyama, Hiromichi Katayama, Norihiko Tsuchiya, Shusuke Akamatsu, Ryoma Kurahashi, Takahiro Kojima, Tomomi Kamba, Koji Yoshimura |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Castration resistant Free dna Cohort Studies chemistry.chemical_compound Prostate cancer Internal medicine Biomarkers Tumor medicine Overall survival Humans Enzalutamide Prospective Studies business.industry Cancer medicine.disease Confidence interval Prostatic Neoplasms Castration-Resistant Abiraterone chemistry business Cell-Free Nucleic Acids |
| Zdroj: | Clinical Cancer Research. 27:6164-6173 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-21-2328 |
| Popis: | 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 patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. Experimental Design: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥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 [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 |
| Databáze: | OpenAIRE |
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