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Clinical Impact of Detecting Low-Frequency Variants in Cell-Free DNA on Treatment of Castration-Resistant Prostate Cancer.
Mizuno, Kei; Sumiyoshi, Takayuki; Okegawa, Takatsugu; Terada, Naoki; Ishitoya, Satoshi; Miyazaki, Yu; Kojima, Takahiro; Katayama, Hiromichi; Fujimoto, Naohiro; Hatakeyama, Shingo; Shiota, Masaki; Yoshimura, Koji; Matsui, Yoshiyuki; Narita, Shintaro; Matsumoto, Hiroaki; Kurahashi, Ryoma; Kanno, Hidenori; Ito, Katsuhiro; Kimura, Hiroko; Kamiyama, Yuki; Sunada, Takuro; Goto, Takayuki; Kobayashi, Takashi; Yamada, Hitoshi; Tsuchiya, Norihiko; Kamba, Tomomi; Matsuyama, Hideyasu; Habuchi, Tomonori; Eto, Masatoshi; Ohyama, Chikara; Ito, Akihiro; Nishiyama, Hiroyuki; Okuno, Hiroshi; Kamoto, Toshiyuki; Fujimoto, Akihiro; Ogawa, Osamu; Akamatsu, Shusuke.
Afiliación
  • Mizuno K; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Sumiyoshi T; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Okegawa T; Department of Urology, Kyorin University School of Medicine, Mitaka, Japan.
  • Terada N; Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Ishitoya S; Department of Urology, Japanese Red Cross Otsu Hospital, Otsu, Japan.
  • Miyazaki Y; Department of Urology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
  • Kojima T; Department of Urology, Faculty of Medicine and Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan.
  • Katayama H; Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Fujimoto N; Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan.
  • Hatakeyama S; Department of Advanced Blood Purification Therapy, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
  • Shiota M; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Yoshimura K; Department of Urology, Shizuoka General Hospital, Sizuoka, Japan.
  • Matsui Y; Department of Urology, National Cancer Center Hospital, Tokyo, Japan.
  • Narita S; Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
  • Matsumoto H; Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
  • Kurahashi R; Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Kanno H; Department of Urology, Yamagata University School of Medicine, Yamagata, Japan.
  • Ito K; Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan.
  • Kimura H; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Kamiyama Y; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Sunada T; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Goto T; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Kobayashi T; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Yamada H; Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan.
  • Tsuchiya N; Department of Urology, Yamagata University School of Medicine, Yamagata, Japan.
  • Kamba T; Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Matsuyama H; Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
  • Habuchi T; Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
  • Eto M; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Ohyama C; Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
  • Ito A; Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Nishiyama H; Department of Urology, Faculty of Medicine and Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan.
  • Okuno H; Department of Urology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
  • Kamoto T; Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Fujimoto A; Department of Human Genetics, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
  • Ogawa O; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Akamatsu S; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. akamats@kuhp.kyoto-u.ac.jp.
Clin Cancer Res ; 27(22): 6164-6173, 2021 11 15.
Article en En | MEDLINE | ID: mdl-34526361
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 <1% is important to identify clinically informative genomic alterations in CRPC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración / Ácidos Nucleicos Libres de Células Tipo de estudio: Clinical_trials / Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración / Ácidos Nucleicos Libres de Células Tipo de estudio: Clinical_trials / Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos