Circulating tumor DNA detection in hepatocellular carcinoma

Cabel, Luc; Proudhon, Charlotte; Bruno, Benedetto; Pierga, Jean‐Yves; Bidard, François-Clément

doi:10.1093/annonc/mdy111

Cited by 5 publications

(4 citation statements)

References 21 publications

(36 reference statements)

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“…A step forward in the diagnosis of HCC could be provided by the development of a "liquid biopsy", i.e., the identification in the peripheral circulation of CTCs or circulating tumor DNA that have detached from a primary tumor [109] . A recent paper reported preliminary data in 8 tumor types, including HCC [110] .…”

Section: Biomarkers For Hcc Diagnosismentioning

confidence: 99%

New and old biomarkers of hepatocellular carcinoma

Zacharakis¹,

AlEid²,

Aldossari³

2018

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Hepatocellular carcinoma (HCC) is a significant cause of mortality in patients with chronic liver disease around the world. Development of biomarkers for early HCC detection is a primary public health goal to decrease mortality. The ideal biomarkers should be highly sensitive and specific for surveillance of high-risk populations and early detection of HCC and also be able to predict therapeutic outcome and provide a prognosis on survival. Currently, the new biomarkers do not perform better than the conventional ones such as alpha-fetoprotein in such a way that they could be widely adopted in clinical practice. Another problem is the low sensitivity of these biomarkers in the detection of HCC. Further work on the development of novel biomarkers and on a combination of them is necessary. Advances in identifying unique molecular signatures including genomic, proteomic, metabolomic, and glycomic profiles have improved our understanding of many biological processes involved in HCC. This review focuses on the role of old and new biomarkers in surveillance, diagnosis, prognosis, and prediction of response to therapeutic targets for HCC and provides up-to-date data to health-care providers which would be applied in clinical practice.

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Section: Biomarkers For Hcc Diagnosismentioning

confidence: 99%

New and old biomarkers of hepatocellular carcinoma

Zacharakis¹,

AlEid²,

Aldossari³

2018

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“…Although these studies employed different assay methods and had cohort sizes that were insufficient for definitive conclusions, ctDNA testing was presumed to be highly specific, with few positives detected in patients with benign liver diseases. Instead, the sensitivity of ctDNA mutation testing tended to be low in early stage HCCs 35,48 . This may be partly attributable to the presence of minimal ctDNA (from small tumours) in blood samples 49 .…”

Section: Discussionmentioning

confidence: 99%

“…Instead, the sensitivity of ctDNA mutation testing tended to be low in early stage HCCs. 35,48 This may be partly attributable to the presence of minimal ctDNA (from small tumours) in blood samples. 49 We also observed low detection rates in early stage cancers, despite applying the use of more advanced and sensitive NGS techniques that involved ultra-high depth and UMI barcoding.…”

Section: Discussionmentioning

confidence: 99%

Applications of molecular barcode sequencing for the detection of low‐frequency variants in circulating tumour DNA from hepatocellular carcinoma

Lee

Kim

Cho

et al. 2022

Liver International

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Purpose Liquid biopsy has emerged as a promising tool for minimally invasive and accurate detection of various malignancies. We aimed to apply molecular barcode sequencing to circulating tumour DNA (ctDNA) from liquid biopsies of hepatocellular carcinoma (HCC). Study Design Patients with HCC or benign liver disease were enrolled between 2017 and 2018. Matched tissue and serum samples were obtained from these patients. Plasma cell‐free DNA was extracted and subjected to targeted sequencing with ultra‐high coverage and molecular barcoding. Results The study included 143 patients: 102 with HCC, 7 with benign liver tumours and 34 with chronic liver disease. No tier 1/2 or oncogenic mutations were detected in patients with benign liver disease. Among the HCC patients, 49 (48%) had tier 1/2 mutations in at least one gene; detection rates were higher in advanced stages (75%) than in early stages (26%–33%). TERT was the most frequently mutated gene (30%), followed by TP53 (16%), CTNNB1 (14%), ARID2 (5%), ARID1A (4%), NFE2L2 (4%), AXIN1 (3%) and KRAS (1%). Survival among patients with TP53 mutations was significantly worse (p = 0.007) than among patients without these mutations, whereas CTNNB1 and TERT mutations did not affect survival. ctDNA testing combined with α‐fetoprotein and prothrombin induced by vitamin K absence‐II analyses improved HCC detection, even in early stages. Conclusions ctDNA detection using molecular barcoding technology offers dynamic and personalized information concerning tumour biology, such information can guide clinical diagnosis and management. This detection also has the potential as a minimally invasive approach for prognostic stratification and post‐therapeutic monitoring.

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“…To address this issue, ctDNA-based liquid biopsy has emerged as a non-invasive approach that allows for the real-time monitoring of tumor dynamics, detection of minimal residual disease, and identification of actionable mutations [ 15 , 16 , 17 , 18 , 19 ]. In patients undergoing liver transplant, the use of cell-free DNA has also been applied to detecting rejection [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Hong,

Wehrle,

Zhang

et al. 2024

Cancers

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Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns.

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Circulating tumor DNA detection in hepatocellular carcinoma

Cited by 5 publications

References 21 publications

New and old biomarkers of hepatocellular carcinoma

New and old biomarkers of hepatocellular carcinoma

Applications of molecular barcode sequencing for the detection of low‐frequency variants in circulating tumour DNA from hepatocellular carcinoma

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

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