TRACE-BTC. Relation of Biomarkers and Patients Reported Quality of Life to Outcomes in Patients With Biliary Tract Cancer: a Real- World Cohort

Purpose of the Study:

Bile duct cancers are rare and aggressive. About 250 new cases are diagnosed each year in Denmark. These cancers are difficult to detect early, so only about 20% of patients can have surgery when diagnosed. Even after surgery, the cancer often returns, and chemotherapy only slightly reduces the risk of relapse.

For patients who cannot have surgery, treatments such as chemotherapy (sometimes combined with immunotherapy) can relieve symptoms and extend life, but their effect is limited. A small number of patients have specific genetic changes in their cancer that can be treated with targeted medicines.

Currently, doctors cannot predict which patients will benefit from treatment. Standard monitoring methods like CT scans are expensive, inconvenient, and sometimes unreliable because bile ducts are hard to see clearly on scans.

Blood tests that detect cancer DNA in the blood (called circulating tumor DNA or ctDNA) and other biological markers may be a better way to monitor the disease and adjust treatment. These tests could help detect cancer recurrence earlier and determine whether treatment is working. Measuring patients' quality of life and symptoms over time may also help predict treatment benefit and evaluate effectiveness.

The goal of this study is to:

• Investigate how biomarkers, including ctDNA, can predict disease course, detect relapse, and monitor treatment response.
• Identify the best way to measure ctDNA in patients with bile duct cancer.
• Examine whether patients' own reports of quality of life and symptoms can help assess treatment effect and prognosis.

Study Design and Procedures:

This is a prospective cohort study focusing on blood biomarkers and patient-reported symptoms and quality of life.

Participants agree to provide blood samples:

• Before treatment
• During treatment
• During follow-up

Each sample involves up to 40 ml of blood, with a maximum of 20 samples per patient.

The blood will be analyzed for:

• ctDNA and genetic changes
• Cancer-related markers
• Inflammation markers
• Immune system markers

Tumor tissue samples will also be examined to compare blood and tissue results. Full genome or exome sequencing will not be performed. Samples will be stored in a research biobank.

For patients with incurable disease, quality of life and symptom burden will be monitored repeatedly using Danish questionnaires.

Participants:

The study will include:

• Up to 100 patients with potentially curable disease
• Up to 200 patients with incurable disease

To participate, patients must:

• Have confirmed bile duct cancer
• Be eligible for curative, additional (adjuvant), or palliative treatment
• Be over 18 years old
• Provide written and verbal consent

Patients cannot participate if they:

• Had another cancer within the past 5 years (except early skin cancer or very early cervical cancer)
• Cannot safely provide blood samples
• Are unable to cooperate with study procedures

Risks and Inconveniences:

Participants will have extra blood samples taken, usually during regular hospital visits. Possible side effects include mild soreness or small bruises at the needle site. The extra blood amount (40 ml per sample) is considered medically insignificant.

Participants will also spend time filling out questionnaires. The number and frequency of questions have been kept as low as possible while still providing meaningful data.

Financial Information:

Extra costs for blood sampling, laboratory analysis, and data collection will be covered by external research funding managed by Aarhus University Hospital.

The researchers have no financial interest in the project. Patients will not receive financial compensation for participating.

Recruitment and Consent:

Potential participants are identified during routine clinical care. During a planned meeting with a doctor, patients receive written and verbal information about the study, including its purpose, risks, advantages, and disadvantages.

The conversation takes place in a calm and private setting. Patients may bring a support person. They have time to ask questions and at least 24 hours to consider participation.

Patients can withdraw their consent at any time without affecting their treatment. Consent must be given before any study-related procedures begin.

Publication of Results:

The results - whether positive or negative - will be presented at national and international conferences and submitted to peer-reviewed scientific journals.

Ethical Considerations:

All participants receive standard medical treatment. The risks and disadvantages are limited, and participants are unlikely to benefit directly from the study. However, the research may improve how biomarkers and patient-reported outcomes are used to predict prognosis and treatment response, potentially leading to better treatment for future patients with bile duct cancer.