Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma

Nakatsuka, Takuma; Nakagawa, Hayato; Hayata, Yuki; Wake, Taijiro; Yamada, Toshimoto; Kinoshita, Mizuki Nishibatake; Nakagomi, Ryo; Sato, Masaya; Minami, Tatsuya; Uchino, Katsuyoshi; Enooku, Kenichiro; Kudo, Yotaro; Tanaka, Yasuo; Kishikawa, Takahiro; Otsuka, Motoyuki; Tateishi, Ryosuke; Koike, Kazuhiko

doi:10.1007/s00535-021-01773-4

Cited by 15 publications

(13 citation statements)

References 44 publications

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“…Circulating tumor DNA (ctDNA), known as tumor-derived cell-free DNA (cfDNA), can be detected in the acellular part of peripheral blood from cancer patients [1]. Since ctDNA contains tumor-specific mutations that represent tumor nature and status, studies on ctDNA have been conducted for various cancer types [2][3][4][5][6][7][8]. Likewise, the potential of ctDNA in colorectal cancer (CRC) as a minimally invasive biomarker has been highlighted in many recent studies for treatment response, prognosis prediction, minimum residual disease (MRD), and recurrence monitoring [9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing

Lee

Kim

Schageman

et al. 2021

Cancers

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The objective of this study was to characterize circulating tumor DNA (ctDNA) mutations in colorectal cancer (CRC) patients and evaluate their prognostic values during treatment. Forty-nine patients with CRC planned for operation were enrolled. A total of 115 plasma samples were collected pre-operation, post-operation, and post-chemotherapy. ctDNA analysis was performed using next-generation sequencing (NGS) including 14 genes. In 22 (44.9%) out of 49 patients, at least one mutation (40 total mutations) was detected in the initial plasma sample. The median sum of variant allele frequency was 0.74% (range: 0.10–29.57%). TP53 mutations were the most frequent (17 of 49 patients, 34.7%), followed by APC (18.4%), KRAS (12.2%), FBXW7 (8.2%), NRAS (2.0%), PIK3CA (2.0%), and SMAD4 (2.0%). After surgery, five (14.3%) out of 35 patients harbored ctDNA mutation. All five patients experienced relapse or metastasis during follow-up. It was noteworthy that all three patients with persistent ctDNA relapsed after R0 resection. After chemotherapy, ctDNA analysis was performed for 31 patients, all of which were ctDNA-negative. Analytical and clinical performances of NGS to utilize ctDNA in CRC were determined. Results revealed that postoperative ctDNA might serve as a marker for identifying risk of recurrence, thus contributing to patient-oriented treatment strategies.

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Section: Introductionmentioning

confidence: 99%

Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing

Lee

Kim

Schageman

et al. 2021

Cancers

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“…Nakatsuka et al found that significant increase in ctDNA levels associate with clinical stage, and a poor prognosis in HCC (50). Moreover, ctDNA levels increased significantly a few days after treatment with molecular-targeted agents such as lenvatinib, and there was a correlation between posttreatment ctDNA levels and therapeutic response.…”

Section: Genomic Signatures Of Circulating Tumor Dnamentioning

confidence: 99%

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

Moldogazieva

Zavadskiy

Terentiev

2021

Cancer Genomics Proteomics

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Hepatocellular carcinoma (HCC) is the sixth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Advanced-stage HCC patients have poor survival rates and this requires the discovery of novel clear biomarkers for HCC early diagnosis and prognosis, identifying risk factors, distinguishing HCC from non-HCC liver diseases, and assessment of treatment response. Liquid biopsy has emerged as a novel minimally invasive approach to enable monitoring tumor progression, metastasis, and recurrence. Since the liquid biopsy analysis has relatively high specificity and low sensitivity in cancer early detection, there is a risk of bias. Next-generation sequencing (NGS) technologies provide accurate and comprehensive gene expression and mutational profiling of liquid biopsies including cell-free circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and genomic components of extracellular vesicles (EVs) including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Since HCC is a highly heterogeneous cancer, HCC patients can display various genomic, epigenomic, and transcriptomic patterns and exhibit varying sensitivity to treatment options. Identification 369 This article is freely accessible online.

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“…107 Another recently published study looking at pre-and posttreatment cfDNA quantification showed that patients who had objective tumor response had a greater increase in posttreatment cfDNA than those without response (p ¼ 0.048), suggesting that the increased cfDNA level a few days after treatment reflects a more efficacious response to therapy. 108 The authors also evaluated posttreatment mutational analysis in lenvatinib responders to identify potential mutations associated with lenvatinib susceptibility. 108 CTCs have also been shown to be useful for treatment allocation.…”

Section: Predicting Treatment Responsementioning

confidence: 99%

“…108 The authors also evaluated posttreatment mutational analysis in lenvatinib responders to identify potential mutations associated with lenvatinib susceptibility. 108 CTCs have also been shown to be useful for treatment allocation. A large study including 299 HCC patients using EpCAM-based CTCs identification could help optimize antitumor strategies.…”

Section: Predicting Treatment Responsementioning

confidence: 99%

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Biomarker Development Using Liquid Biopsy in Hepatocellular Carcinoma

Grinspan

Villanueva

2022

Semin Liver Dis

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Liver cancer incidence rate continues to increase and currently ranks third in the total number of annual deaths, behind only lung and colorectal cancer. Most patients with hepatocellular carcinoma (HCC) are diagnosed at advanced stages, and they live for less than 2 years after diagnosis on average. This contrasts with those diagnosed at an early stage, who can be cured with surgery. However, even after curative resection, there remains a risk of up to 70% of postoperative HCC recurrence. There have been major changes in the management of HCC in the past 5 years, particularly for patients at advanced stages. Despite this multitude of new therapies, there is a lack of clear biomarkers to guide providers on the best approach to sequence therapies, which would maximize efficacy while minimizing toxicity. There are several areas in clinical management of HCC that are particularly challenging, and would benefit from development and implementation of new biomarkers to improve patient overall survival. Here, we review the major advances in liquid biopsy biomarkers for early detection of HCC, minimum residual disease, and predicting response to treatment.

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Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma

Cited by 15 publications

References 44 publications

Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing

Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

Biomarker Development Using Liquid Biopsy in Hepatocellular Carcinoma

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