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Disease Attributes

Herpes Simiae (B Virus)

Pei-Jer Chen, Ph.D

HBV DNA integration has been found in the chromosomes of about 90% of HBV-related HCC and the integration site is unique to individual HCC. The virus-host chimera DNA (vh-DNA) from HBV integration sites in HCC a reliable evidence even in the patient with a tiny tumor which is not large enough to be detected by the image scan.

The goal of this observational study is to compare the prediction ability of vh-DNA with the other biomarkers for monitoring the recurrent of HBV-related HCC. The main questions that aim to answer are the sensitivity and specificity of vh-DNA/AFP/ALP-L3/PIVKA-II/TERTC2280 when the gold standard is the guideline of HCC diagnosis.

The surgical tissues and plasma samples from the participants would be collected undergoing the HCC recession surgery when joining the study at the beginning, in order to identify the HBV integration in tumor by Capture NGS and quantify the specific vh-DNA in plasma by ddPCR as personalized biomarkers for minimal residual disease (MRD) monitoring. Moreover, the consistency of vh-DNA from tumor will be validated by pre-operative plasma.

Then the participants will be asked to performed the visit at 2, 5, 8, 11, 14 months after the HCC recession surgery. The plasma sample for vh-DNA/AFP/ AFP-L3/ PIVKA-II/ TERTp C228T testing and the image data from ultrasound, CT or MRI would also be collected at these visits. When the vh-DNA testing result is positive and there is no recurrence at 14 months after the HCC recession surgery, some participants will be asked to followed at 17, 20 months.

Researcher will compare the sensitivity, specificity and predict day of vh-DNA with AFP/ AFP-L3/ PIVKA-II/ TERTp C228T as a biomarker for HCC surveillance. The true value of this novel HBV chimera vh-DNA will be revealed. The results will also support to use for monitoring post-operative recurrence.

In addition, the investigators will explore the performance of TERTp C228T mutation from non-HBV HCC patients. As a different target of ctDNA for HCC, TERTp C228T will be identified using surgical tissues from HCC patients, and plasma samples from the same patient before/after operation will be tested by ddPCR . It will be evaluated that TERTp C228T is predictive or not for recurrence monitoring of HCC.

Cell-free DNA From Junction of Hepatitis B Virus Integration in HCC Patients for Monitoring Post-resection Recurrence

Cell-free DNA From the Junction of Hepatitis B Virus Integration in HCC Patients for Monitoring Post-resection Recurrence: A Comparison Study With Current Biomarkers

Compare the sensitivity of vh-DNA with AFP as a biomarker for HCC surveillance.

Compare the sensitivity of vh-DNA with AFP-L3/ PIVKA-II/ TERTp C228T as a biomarker for HCC surveillance.

Compare the specificity of vh-DNA with AFP/ AFP-L3/ PIVKA-II/ TERTp C228T as a biomarker for HCC surveillance.

Compare the predicted day of vh-DNA with AFP/AFP-L3/PIVKA-II/TERTp C228T as a biomarker before HCC recurrence.

To clarify the clonality of recurrent HCC is same as the original one or is a de novo one.

Compare the sensitivity of TERTp C228T with AFP/ AFP-L3/ PIVKA-II as a biomarker for HCC surveillance.

National Taiwan University Hospital

TCM Biotech International Corp.

Neoplasm, Residual

Neoplastic Processes

Pei-Jer Chen, MD-PhD

Shiou-Hwei Yeh, Ph.D.

Pei-Jer Chen, MD/PhD

Shiou-Hwei Yeh, PhD

Early stage HCC is treated by curative surgical resection or by local ablation (such as radio-frequency) as the current standard of care. The complete removal of clinical visible HCC is then confirmed by imaging by MRI or CT, or by a decline of tumor marker (AFP or PIVKA). However, despite an apparent complete removal of the HCC, those post-curative patients frequently develop tumor recurrence at a rate ranging 10-50% within the first year. The high rate of early HCC recurrence indicated a minimal residual HCC after the curative therapies in a significant proportion of patients. A better and more specific biomarker for detecting the residual HCC will improve the patients' prognosis prediction and therapeutic plan.

To detect the minimal residual HCC, a biomarker unique to the tumor is needed. Currently, the cell-free circulating DNA carrying tumor-specific somatic mutations has been advocated as a promising one. It has been applied to investigate the tumor responses or resistances to cancer therapy. However, currently it is restricted to detect or follow only large advanced cancer, because of the difficulty in separating or enriching the cfDNA with tumor-specific mutations from the cfDNA from normal cells. In this project, the investigators proposed that one class of somatic mutation in HBV-related HCC, namely the insertion mutagenesis by integrated HBV DNA, could be adopted to circumvent this difficulty. HBV DNA integration has been found in the chromosomes of about 90% of HBV-related HCC and the integration site is unique to individual HCC. The HBV-host junction DNA fragment from one HCC is therefore a tumor-specific biomarker. Such fragments can be released into the circulation as cell-free circulating DNAs, and the detection of the HBV-host chimera DNAs in the circulation is a reliable evidence for the presence of the tumor in the patient. Therefore the cf circulating HBV-host chimera DNA is proposed to assay any minimal residual HCC after curative therapies.

Development stages:

Stage I: Identification of integrated HBV DNA sites in HBV-related HCC tissues. the investigators will develop either HBV-specific inverse PCRs or capture-sequencing protocols to identify HBV integrations sites in the tumor chromosomes. The viral-host junction sequences of individual HCC identified and used as the template for developing assays for detecting the same HBV-host chimera DNA fragment in the circulation.

Stage II: New platforms to accurately detect or even quantitate the circulating vh-chimera DNA fragment.

These tumor-specific vh-chimera DNA will only represent a tiny fraction of total cfDNAs. However, as these sequences of the tumor-specific vh-chimera DNA have been known from stage 1, the investigators may develop better and more specific assays for quantitation.

Stage III: Assays for cell-free tumor specific vh-chimera DNA applied to the blood samples from post-curative HCC patients.

To demonstrate the efficacy of these assays, blood samples obtained at 4 weeks after curative therapies from 50 HBV-related HCC patients, and tested for the presence of cf tumor-specific vh-chimera DNAs. The presence or absence of such vh-chimera DNA will be correlated with the early HCC recurrence within the first year to determine any clinical significance. There will be one blood sampling at the time of HCC recurrence.

Sample collection In stage I and II, the investigators will set up methods for chimera DNA identification and quantification, which need tumor samples to support the development and evaluation of the feasibility for each assay. Therefore, the investigators will apply the approval for use the tissues from the Taiwan Liver Cancer Network (TLCN), including 20 pairs of HBV-related male HCC, 20 pairs of HBV-related female HCC (for positive control), 20 pairs of HCV related male HCC, 20 pairs of HCV related female HCC (for negative control), 20 pairs of HBV- and HCV-related male HCC, and 20 pairs of HBV- and HCV-related female HCC (to see if vh-chimera DNA is also applicable for HBV- and HCV-related HCC). Both the genomic DNA and RNA will be applied for these 120 patients in total. Genomic DNA will be used in assay development, including identification, detection and quantification; whereas RNA will be used in validation of the insertional mutagenic RNA transcripts, which will provide supporting evidence for tumor specific integration from transcription level.

In stage III, the investigators will investigate whether there is any correlation between tumor-specific vh-chimera DNA level and recurrence-free survival using the assays the investigators developed in stage I and II. Therefore, the investigators will collect the Tumor (T) and non-Tumor (NT) tissue pairs from 50 HBV-related HCC patients that receive surgical removal of tumor, and also the peripheral blood at 4w after surgery. T and NT tissues are for vh-chimera DNA identification, peripheral blood will be used for vh-chimera DNA detection and quantification. On the other hand, clinical information including tumor size, tumor grade, serum markers from routine liver function test (ALT, AST), current HCC marker (AFP), and recurrence-free survival time will be collected for correlation study. All data will be stored in computer with password protection.

Tumor (T) and non-Tumor (NT) tissue, and peripheral blood.

HBV-host cfDNA as Minimal Residual Tumor Marker for HBV-related HCC

A New Biomarker for Detection of Minimal Residual Tumor in Hepatitis-B Virus Related Hepatocellular Carcinoma After Curative Therapies: The Cell-free Circulating HBV-host Chimera DNA Fragment

Detection of the HBV-host chimera DNA in blood sample.----- one blood sampling at the time of HCC recurrence.

clinical information about HCC recurrence. detection by CT or MRI.

clinical information about HCC recurrence.

Chia-Hsien Cheng

The investigators will first use our previously collected serum samples and surgical/biopsied tissues from HBV-related HCC patients undergoing radiotherapy. The consistency of junctional clones by Capture NGS needs to be tested between both pre- and post-RT serums, and serial changes in copy numbers of vh-DNA by ddPCR are quantified in the representative cases. The same junction clones from pre-post-RT serums and surgical tissues will be confirmed and the copy number changes of vh-DNA be correlated with RT response and disease-control status.

The investigators plan to identify HBV integrations by Capture NGS and quantify the specific vh-DNA by ddPCR as personalized biomarkers from the same-patient serum samples. The investigators will further correlate clinical response and recurrence/metastasis with serial changes of vh-DNA copy numbers. The investigators have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis. The investigators plan to confirm the viable role of pre-/post-RT changes of plasma vh-DNA copies of the same junction clone in post-RT response and prognosis. Moreover, The investigators will explore the recurrent/metastatic tumors arising from the original or a de novo one by identifying their clonality with HBV integration patterns. The true value of this novel HBV chimera vh-DNA will be revealed. The results will also support the consolidative use of personalized vh-DNA for earlier evaluating treatment response after RT, for post-RT disease monitoring, and for differentiating clonality at recurrence to design future clinical trial on combinational treatment.

Residual tumors and early recurrence/metastasis after radiotherapy (RT) compromise the patient survival with hepatocellular carcinoma (HCC). Timely detecting residual/recurrence/metastasis and the clonality is required to implement salvage therapies properly. The major unmet needs of radiotherapy to HCC are the difficulties in early evaluating response by images and timely detection of intrahepatic recurrence and extrahepatic metastasis. Thus, an accurate and personalized biomarker for response prediction and disease monitoring is demanded. Cell-free tumor-specific DNA (ctDNA) has garnered attention as a promising biomarker in cancer patients. However, in HCC, the detection rate is low (9-21.2%), mainly due to the limited prevalence of traditional somatic mutations and the difficult separation of ctDNA fragments from normal cells. The investigators aim to develop a novel ctDNA, the virus-host chimera DNA (vh-DNA), as a biomarker for hepatitis B virus (HBV)-related HCC patients undergoing RT. HBV vh-DNA presents in \~90% of HBV-related HCC patients and can be differentiated from DNA released from the normal cells through enrichment by capturing with HBV probes. vh-DNA might be advantageous to the traditional somatic mutation type of ctDNA. The investigators hypothesize that HBV vh-DNA could accurately diagnose residual tumor by 6-12 months earlier than contemporary images and predict early recurrence/metastatsis, thus allows early intervention of salvage therapies.

The investigators will first use our previously collected serum samples and surgical/biopsied tissues from HBV-related HCC patients undergoing radiotherapy. The consistency of junctional clones by Capture NGS needs to be tested between both pre- and post-RT serums, and serial changes in copy numbers of vh-DNA by ddPCR are quantified in the representative cases. The same junction clones from pre-post-RT serums and surgical tissues will be confirmed and the copy number changes of vh-DNA be correlated with RT response and disease-control status.

The investigators plan to identify HBV integrations by Capture NGS and quantify the specific vh-DNA by ddPCR as personalized biomarkers from the same-patient serum samples. The investigators will further correlate clinical response and recurrence/metastasis with serial changes of vh-DNA copy numbers. The investigators have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis. The investigators plan to confirm the viable role of pre-/post-RT changes of plasma vh-DNA copies of the same junction clone in post-RT response and prognosis. Moreover, The investigators will explore the recurrent/metastatic tumors arising from the original or a de novo one by identifying their clonality with HBV integration patterns. The true value of this novel HBV chimera vh-DNA will be revealed. The results will also support the consolidative use of personalized vh-DNA for earlier evaluating treatment response after RT, for post-RT disease monitoring, and for differentiating clonality at recurrence to design future clinical trial on combinational treatment.

We plan to identify HBV integrations by Capture NGS and quantify the specific vh-DNA by ddPCR as personalized biomarkers from the same-patient serum samples.

A Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma

Developing a Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma Treated With Radiotherapy: Personalized Cell-free Virus-host Chimera DNA

Capture-NGS analysis and identification of HBV-human junction between pre- and post- RT

Vh-DNA specific PCR between pre- and post- RT

Treatment response between pre- and post- RT

Calculate the percentage of identical vhDNA sets between the simultaneously collected serum and plasma samples in the same patients

Treatment response will be determined as the best response in serial image follow-ups up to 6 months after completion of RT. Responses will be classified as completion response, partial response, stable disease, and progressive disease by the definition of mRECIST.

It will be calculated from the last fraction of radiotherapy until death from any cause of last follow-up.

Detected tumor-specific vh-DNA in the plasma collected at the time of recurrence/metastasis to determine its clonality.

Study title	NCT ID	Conditions	Eligibility	Organization
Cell-free DNA From Junction of Hepatitis B Virus Integration in HCC Patients for Monitoring Post-resection Recurrence	NCT05823584	Hepatocellular ...	20 Years -	TCM Biotech International Corp.
HBV-host cfDNA as Minimal Residual Tumor Marker for HBV-related HCC	NCT03020342	Carcinoma, Hepa...	20 Years -	National Taiwan University Hospital
A Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma	NCT05752890	Hepatocellular ... Hepatitis b Vir... Radiotherapy Biomarker	18 Years -	National Taiwan University Hospital

Spots Global Cancer Trial Database for chimera dna

Every month we try and update this database with for chimera dna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for chimera dna

Every month we try and update this database with for chimera dna cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for chimera dna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.