National clinical study

ISCOLIM: Improving Survival of Colo-rectal Liver Metastases by RFA-mediated Immuno-stimulation

We will explore the use of ctDNA as a biomarker for prediction of incipient recurrence. The assessment will be made both at milestone time-points and by serial analysis. We will explore if ctDNA can detect recurrence before standard-of-care CT-imaging. We will explore if ctDNA can help guide clinical decision making at time-points where the CT-imaging results are indeterminate, which is the case in approximately 20% of all CT-scans.

ClinicalTrials.gov: NCT04798898

The project received funding in 2022

Abstract

Each year 1,600 Danish individuals are diagnosed with colorectal cancer liver metastases (CRLM). Patients with non-resectable metastases have a relative 5-year survival rate of only 14%. Curatively intended resection of CRC liver metastases (CRLM) can increase survival by up to 40%. In Denmark curatively intended CRLM resection is performed on ~25% of CRLM patients, these are the patients with oligo-metastatic disease, who are fit for surgery, and for which at least 30% of the liver parenchyma can be preserved after resection. While CRLM resection remains state-of-the-art for treatment of CRLM, the risk of relapse remains high, with nearly 50% recurring within two years.

Efficient post-operative surveillance may enable early detection of recurrence when the recurrence lesion is still treatable. This may improve survival as repeated surgery has been documented to be an effective treatment for both liver and lung recurrences after CRLM resection. Unfortunately, evidence is lacking to guide the design of an efficient surveillance strategy for CRLM-resected patients. Consequently, international consensus for post-CRLM-resection surveillance is limited. Generally, surveillance programs include computed tomography (CT) and carcinoembryonic antigen (CEA) assessment, but surveillance intensity varies between programs. Given the paucity of evidence and international consensus, studies addressing CRLM surveillance are critically needed.

Non-invasive, serial analysis for circulating tumor DNA (ctDNA) has emerged as a promising tool for post-surgery surveillance of CRLM. We have recently demonstrated some of the many potential benefits of adding a ctDNA test, such as the tumor agnostic DNA methylation test, TriMeth, to the existing CRLM surveillance program. However, additional evidence is needed before implementation.

Here we propose to assess the clinical pertinence of implementing serial TriMeth ctDNA analysis in future CRLM surveillance programs, by performing observational TriMeth follow-up in a large protocolled prospective CRLM follow-up study, within the framework of the Danish randomized trial “ISCOLIM”.

We will explore the prognostic power of TriMeth at landmark time-points (post-surgery and post adjuvant chemotherapy (ACT)), and if serial TriMeth can detect CRLM recurrence before standard-of-care CT imaging, and whether TriMeth can help guide clinical decision making at time-points where the CT-imaging results are indeterminate (~20% of all CT-scans).

The perspective of the study is improved surveillance, better postoperative risk stratification, earlier detection of recurrence, improved risk assessment at indeterminate CT-scans, and earlier and more effective treatment of CRLM recurrence.

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