ctDNA Monitoring in Patients With HCC and mCRC

Summary

"Liquid biopsy" is a collective term that refers to the analysis of cancer-derived biomarkers isolated from the biological fluids of cancer patients. The analysis of these blood components can be used for early cancer detection, staging, prognosis, drug resistance monitoring, and minimal residual disease (MRD) monitoring. The "liquid biopsy" is based on the fact that cancer cells release their DNA into the bloodstream, known as ctDNA (circulating tumor DNA). A sample of the patient's peripheral blood is sufficient to test ctDNA. There have been many studies in the literature on the usefulness of liquid biopsy in the treatment of various malignancies, such as breast cancer, prostate cancer, and colorectal cancer. However, this has been a lack of prospectively obtained data analyzing the impact on the ctDNA assessment of the progression and recurrence of the primary disease or the type of treatment applied to improve long-term survival. The ctDNA test is not a widely recognized technology for assessing the progression of neoplastic disease.

Aim of the study/research hypothesis: the aim of the project is to clinically validate the value of the ctDNA test as a tool for early diagnosis of recurrence, assessment of cancer progression, the prognosis of treatment effects, and monitoring of therapy in patients with primary liver HCC or colorectal cancer metastases.

Description of the methodology: The main objective of the work will be achieved through the implementation of specific objectives: 1) Recruitment of 300 patients, including 100 patients with colorectal liver limited metastasis, 100 patients with hepatocellular carcinoma (HCC) and 100 patients in the control group who will be qualified for liver resection or transplantation, and in whom ctDNA level testing will not be tested. 2) Taking blood samples from the patients. The detection of ctDNA requires only the collection of 10 ml of the patient's blood and the collection of specimens from the tumor after resection. Blood will be collected before, one month, and 6 months after surgery during routine oncology check-ups. Tumor specimens will be taken from the backside table and sent for final histopathological examination. Control "follow-up" will take place for 18 months from the first ctDNA blood collection.

Based on the collected material, genetic analysis will be performed. In the first stage, a tumor section taken during liver resection, and DNA from the patient's blood will be analyzed the molecular (genetic) signature of the patient's tumor will be determined and several genetic changes characteristic of the change will be selected. Thereafter, the presence of the selected genetic variants will be assessed qualitatively and quantitatively in the pre-operative blood sample and all subsequent post-operative blood samples.

The investigators assume that in a blood sample taken 4 weeks after surgery, ctDNA should be undetectable or detected at a low level. In order to assess the change in the level of ctDNA in the postoperative period, a third examination will be performed - 6 months after the operation. Any level of detected ctDNA will be considered significant.

Each increase in the level of the analyzed mutations will indicate the potential progression of the disease. The results of molecular analyzes will be correlated with the assessment of imaging tests and the level of tumor markers performed as part of routine oncological control.

This is a prospective observational study with a defined study group. These are patients with colorectal cancer metastases limited to the liver, i.e. stage IV of the cancer process, or patients with hepatocellular carcinoma (HCC) qualified for radical surgery or liver transplantation. Patients in the control group (without ctDNA tests) will be treated in accordance with the best clinical knowledge and accepted international recommendations.

The statistical analysis of the results will use the SAS (Statistical Analysis System) software, considering the Kaplan-Meier method, log-rank tests, Cox proportional hazards regression, and logistic regression.

The investigators hypothesize that the use of ctDNA will enable the identification of early disease progression or will identify patients with the highest risk of recurrence. In addition, it will improve the supervision of diseases and enable possible modification of treatment in patients with stage IV colorectal cancer or patients after liver resection or transplantation for HCC. In the future, oncological prevention will consist in blood tests, which will enable early detection of even those cancers that show symptoms only at an advanced stage, which will potentially improve the effectiveness of treatment.

Conditions

• HCC - Hepatocellular Carcinoma
• Colorectal Cancer Metastatic

Interventions

DIAGNOSTIC_TEST

Tumor Tissue Collection and NGS

Tumor tissue is collected during surgery and used for DNA extraction. Next-Generation Sequencing (NGS) is performed to identify oncogenic mutations.

OTHER

Blood Collection for Plasma ctDNA

Blood is collected at three time points: one day before surgery, one month, and six months after surgery. Plasma is separated and used for further molecular analysis or storage.

DIAGNOSTIC_TEST

ctDNA Mutation Analysis via ddPCR

Circulating tumor DNA (ctDNA) is isolated from plasma samples. Mutations previously identified by NGS are quantitatively analyzed using droplet digital PCR (ddPCR).

Sponsors & Collaborators

• Medical Research Agency, Poland

  collaborator OTHER_GOV

• Medical University of Warsaw

  lead OTHER

Principal Investigators

• Tomasz Stokłosa, Professor · [email protected]

Study Design

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

SINGLE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-01

Primary Completion

2027-02-01

Completion

2028-04-30

Countries

• Poland

Study Locations