This is a combined prospective and retrospective observational study aiming to validate a highly sensitive and specific blood-based method for the early diagnosis and post-treatment monitoring of multiple cancers. The study leverages a newly developed sequencing method to improve the detection of circulating tumor DNA (ctDNA) in blood, focusing on enhancing sensitivity and specificity in clinical applications.
The study targets patients with ovarian, lung, pancreatic, colorectal, esophageal, breast, kidney, bladder, and gastric cancer, as well as healthy controls with asymptomatic gallstones, benign polyps, or individuals undergoing routine medical screening. Blood samples will be analyzed for cell-free DNA (cfDNA), RNA, and protein profiles. A key objective is to determine how much the newly developed method increases the sensitivity and specificity of ctDNA detection, especially in early-stage cancers and minimal residual disease (MRD) after treatment.
The method evaluates the variant allele frequency (VAF) of ctDNA to detect residual disease and track tumor dynamics. Serial blood sampling will be conducted before and after surgery or chemotherapy and during follow-up outpatient visits in cancer patients, while one-time sampling will be done for controls. Additionally, tissue biopsies collected during surgery will be used to analyze concordance between tumor-specific mutations and those found in ctDNA.
Primary outcome measures include quantitative differences in ctDNA or RNA levels between cancer and control groups. Secondary outcomes assess the clinical correlation between changes in ctDNA VAF and patient outcomes such as recurrence and survival. Statistical tools including ROC curve analysis, Cox regression, and log-rank tests will be used to quantify performance.
This study seeks to establish a clinically robust, non-invasive diagnostic tool that enables earlier detection and more precise treatment decisions, while potentially reducing physical, psychological, and socioeconomic burdens related to cancer care.
Age ≥ 19 years
Voluntarily agreed to participate and provided informed consent
Able to donate blood without health risks
Underwent or is scheduled to undergo surgery or chemotherapy for therapeutic purposes for cancer (for cancer group)
Age < 19 years
Patients with mental retardation or severe psychiatric disorders affecting informed consent
History of HIV, HTLV, or syphilis infection
History of other malignancy within 5 years (for cancer group)
Participants will be recruited from patients and screening subjects at Yonsei University Health System (Severance Hospital, Yonsei Cancer Center, and affiliated check-up centers in Seoul, South Korea). The study population includes individuals diagnosed with ovarian, lung, pancreatic, colorectal, esophageal, breast, bladder, kidney, or gastric cancers, either newly diagnosed or post-treatment. The control group includes individuals with asymptomatic gallstones, benign polyps, or those undergoing routine health screenings. All participants must be 19 years or older and able to provide informed consent for blood collection and data/sample usage.
Case-control
Retrospective
Serial Blood Sampling for Molecular Profiling
Other interventionCancer patients will undergo serial peripheral blood sampling at baseline (prior to surgery or chemotherapy), after treatment, and during follow-up visits. Blood samples will be analyzed for circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), RNA, and protein biomarkers. The purpose is to detect variant allele frequency (VAF) and evaluate its relationship with tumor dynamics and treatment outcomes, including recurrence and survival.
One-Time Blood Sampling for Molecular Profiling
Other interventionControl participants, including individuals with asymptomatic gallstones, benign polyps, or those undergoing health screening, will provide a one-time peripheral blood sample. The sample will be analyzed for cfDNA, RNA, and protein biomarkers and used as a baseline reference to compare molecular characteristics between non-cancer and cancer groups.
Difference in significantly detected ctDNA Variant Allele Frequency (VAF) between Cancer Patients and Controls
Quantitative measurement of significantly detected ctDNA variant allele frequency (VAF) in plasma samples from blood collected at baseline and follow-up visits (every 3-12 months up to 2 years) will be used to assess sensitivity and specificity of the developed sequencing method in detecting cancer-associated mutations. ROC curve analysis will be applied to determine the method's diagnostic performance (e.g., AUC).
Correlation between ctDNA VAF and Clinical Outcomes (Recurrence and Survival)
To evaluate the relationship between ctDNA variant allele frequency (VAF) changes and patient clinical outcomes, including recurrence free and overall survival. Longitudinal VAF trends will be correlated with disease progression. Additionally, concordance between ctDNA mutations and matched tumor tissue mutations will be assessed. In patients receiving chemotherapy, detection of resistance-related mutations in ctDNA will be evaluated for associations with treatment outcomes. Survival analysis will use Cox regression and log-rank tests.
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