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Identification and monitoring of mutations in circulating cell-free tumor DNA in hepatocellular carcinoma treated with lenvatinib.
Fujii, Yasutoshi; Ono, Atsushi; Hayes, C Nelson; Aikata, Hiroshi; Yamauchi, Masami; Uchikawa, Shinsuke; Kodama, Kenichiro; Teraoka, Yuji; Fujino, Hatsue; Nakahara, Takashi; Murakami, Eisuke; Miki, Daiki; Okamoto, Wataru; Kawaoka, Tomokazu; Tsuge, Masataka; Imamura, Michio; Chayama, Kazuaki.
Affiliation
  • Fujii Y; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Ono A; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Hayes CN; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Aikata H; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Yamauchi M; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Uchikawa S; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Kodama K; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Teraoka Y; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Fujino H; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Nakahara T; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Murakami E; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Miki D; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Okamoto W; Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan.
  • Kawaoka T; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Tsuge M; Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
  • Imamura M; Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
  • Chayama K; Collaborative Research Laboratory of Medical Innovation, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. chayama@mba.ocn.ne.jp.
J Exp Clin Cancer Res ; 40(1): 215, 2021 Jun 26.
Article in En | MEDLINE | ID: mdl-34174931
ABSTRACT

BACKGROUND:

There has been a recent surge in interest in predicting biological effects associated with genomic alterations in order to implement personalized cancer treatment strategies. However, no reports have yet evaluated the utility of profiling blood-based circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN).

METHOD:

We retrospectively performed ctDNA next-generation sequencing (NGS) analysis in 24 patients with advanced HCC at baseline and 4 weeks after initiation of LEN. Association of the changes in variant allele frequencies (VAFs) during treatment and clinical outcome were evaluated.

RESULTS:

In total, 131 single nucleotide variants, 17 indels, and 23 copy number variations were detected as somatic alterations in 28, 6, and 12 genes, respectively in 23 of 24 patients. The most frequently altered genes were TP53 (54%), CTNNB1 (42%), TERT (42%), ATM (25%), and ARID1A (13%). The reduction in the mean frequency of variants (VAFmean) following 4 weeks of LEN treatment was associated with longer progression-free survival. The specificity and sensitivity of the reduction of VAFmean for predicting partial response were 0.67 and 1.0, respectively, which were higher than those of serum α-fetoprotein level (0.10 and 0.93, respectively). No association between the mutation status at baseline and the effectiveness of LEN was observed.

CONCLUSION:

Our study demonstrated that somatic alterations could be detected in the majority of advanced HCC patients by ctDNA profiling and that ctDNA-kinetics during LEN treatment was a useful marker of disease progression. These results suggest that ctDNA profiling is a promising method that provides valuable information in clinical practice.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phenylurea Compounds / Quinolines / Sequence Analysis, DNA / Carcinoma, Hepatocellular / Circulating Tumor DNA / Liver Neoplasms / Mutation / Antineoplastic Agents Type of study: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: J Exp Clin Cancer Res Year: 2021 Document type: Article Affiliation country: Japan

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phenylurea Compounds / Quinolines / Sequence Analysis, DNA / Carcinoma, Hepatocellular / Circulating Tumor DNA / Liver Neoplasms / Mutation / Antineoplastic Agents Type of study: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: J Exp Clin Cancer Res Year: 2021 Document type: Article Affiliation country: Japan