Clinical Utility of ctDNA in the Treatment of Oligometastatic Disease

Clinical Utility of ctDNA in the Treatment of Oligometastatic Disease - A Prospective Observational Clinical Study - A Part of the POB-project

This prospective observational study investigates the clinical utility of circulating tumor DNA (ctDNA) in patients with oligometastatic disease (OMD) undergoing definitive-intent local ablative treatment (LAT). The study aims to evaluate ctDNA as a prognostic and response biomarker before, during, and after LAT across cancer types and treatment modalities. Serial plasma samples and archival tumor tissue will be analyzed to assess ctDNA detection rates, elimination patterns, minimal residual disease, and association with recurrence, progression, and survival outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Oligometastatic Cancer

Detailed Description

Oligometastatic disease (OMD) represents an intermediate disease state between localized and polymetastatic cancer and may be amenable to curative or long-term disease-controlling local ablative treatment (LAT). Despite careful patient selection, recurrence rates after LAT remain substantial, highlighting the need for improved biological markers to guide treatment decisions and follow-up.

Circulating tumor DNA (ctDNA) is a promising biomarker for prognostication, response assessment, and early detection of recurrence. Pilot studies and systematic reviews conducted by the study group indicate that ctDNA dynamics before and after LAT are associated with treatment outcomes. However, important knowledge gaps remain regarding ctDNA detection rates, elimination patterns, optimal sampling time points, and clinical relevance across metastatic sites, treatment modalities, and oligometastatic states.

This prospective observational study, conducted as part of the Pan-Cancer Oligometastatic Biology (POB) project, will enroll patients with oligometastatic solid tumors planned for definitive-intent LAT. Serial blood samples will be collected before treatment, during treatment when applicable, and throughout follow-up. ctDNA and total circulating free DNA will be analyzed using sensitive molecular techniques. Archival tumor tissue will be retrieved for tumor-informed analyses.

The study will evaluate ctDNA detection rates, elimination patterns, minimal residual disease, lead time to radiological recurrence, and associations with disease-free survival, progression-free survival, and overall survival. Exploratory analyses of immune-related biomarkers will also be performed. The results are expected to support improved biological stratification and monitoring strategies in oligometastatic disease.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Louise B Callesen, MD, PhD; Phone Number: 30482884; Email: Louicall@rm.dk
• Study Contact Backup: Name: Karen-Lise G Spindler, Professor, MD, PhD; Phone Number: 91167244; Email: K.g.spindler@oncology.au.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Department of Oncology, Aarhus University Hospital
    • Contact: Louise B Callesen, MD, PhD; Phone Number: 30482884; Email: Louicall@rm.dk
    • Principal Investigator: Louise B Callesen, MD, PhD
    • Principal Investigator: Karen-Lise G Spindler, Professor, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients with verified oligometastatic cancer disease who are planned for local ablative therapy.

Description

Inclusion Criteria:

• Metastatic spread from histopathological diagnosed solid cancer
• Planned for LAT (local ablative therapy) for OMD (oligometastatic disease)
• ≥ 18 years
• Written and oral consent

Exclusion Criteria:

• Other cancer disease within 5 years
• Conditions that will contraindicate blood samples

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between longitudinal ctDNA status and clinical outcomes after local ablative treatment	Presence and dynamics of circulating tumor DNA (ctDNA) assessed before LAT, after LAT, and during follow-up, and their association with clinically relevant outcomes including radiologically confirmed recurrence or progression, survival status, and lead time to recurrence.	During follow-up up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection rate of ctDNA prior to local ablative treatment	The proportion of patients with detectable circulating tumor DNA in plasma prior to initiation of local ablative treatment will be assessed. Detection rates will be evaluated overall and stratified by treatment modality, cancer type and metastatic site	Baseline (pre-LAT)
Elimination patterns of ctDNA following local ablative treatment	Changes in ctDNA levels following local ablative treatment will be analyzed to characterize elimination patterns over time. Changes in ctDNA will be assessed in relation to treatment modality, cancer type, metastatic site, and timing of sampling to evaluate biological response to treatment	During follow-up up to 5 years
Correlation between ctDNA and pathological response	ctDNA status and ctDNA changes will be correlated with pathological response	During follow-up up to 5 years
Correlation between ctDNA and risk of recurrence or early progression	The association between ctDNA and the subsequent risk of recurrence or early disease progression will be evaluated	Up to 5 years
Correlation between ctDNA and disease-free survival or progression-free survival	Disease-free survival or progression-free survival will be analyzed according to ctDNA status at baseline, post-treatment, and during follow-up to assess the prognostic value of ctDNA in patients treated with definitive-intent local ablative treatment	Up to 5 years
Correlation between ctDNA and overall survival	Overall survival will be analyzed according to ctDNA status at baseline, post-treatment, and during follow-up to assess the prognostic value of ctDNA in patients treated with definitive-intent local ablative treatment	Up to 5 years
Rate of ctDNA-detected minimal residual disease	The proportion of patients with detectable ctDNA following completion of definitive-intent local ablative treatment, consistent with molecular minimal residual disease, will be determined and analyzed in relation to clinical outcomes	up to 5 years
Lead time between ctDNA detection and imaging-confirmed recurrence or progression	The time interval between first detection of ctDNA during follow-up and subsequent radiological confirmation of recurrence or progression will be calculated to estimate the potential lead time provided by ctDNA monitoring	During follow-up up to 5 years
Exploratory analysis of total circulating free DNA	Total circulating free DNA levels will be quantified and analyzed exploratorily in relation to treatment, ctDNA status, imaging findings, and clinical outcomes to assess potential additional biological or prognostic value	Up to 5 years

Collaborators and Investigators

• Sponsor: Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Local Ablative Treatment of Oligometastatic Disease
• Other Study ID Numbers: 1-10- 72-122-25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No