Radiogenomic Profiling of Dendritic Cells and Macrophages to Predict Recurrence in Colorectal Liver Metastasis

NCT07744139 | Not Yet Recruiting

• 1 other identifier: 27482
• Study Type: observational
• Target: 210
• Locations: 0 countries
• Sites: N/A

Brief Summary

The RaP-DMac-LiMe study (Radiogenomic Profiling of Dendritic Cells and Macrophages to Predict Recurrence in Colorectal Liver Metastasis) is a monocentric, non-profit observational study promoted by Fondazione Policlinico Universitario A. Gemelli IRCCS. Its primary aim is to identify immunological, genomic, and radiomic biomarkers associated with recurrence risk in patients with colorectal liver metastases (CRLM) undergoing curative-intent liver resection. The study is based on the need to improve prognostic stratification in CRLM by integrating information from the tumor immune microenvironment, tumor genomics, radiomics, and clinical data. Particular attention is given to myeloid immune cells, especially dendritic cells and tumor-associated macrophages, whose role in metastatic progression and recurrence remains insufficiently understood. The primary objective is to assess the association between myeloid immune profiles and recurrence risk through integrated molecular, spatial, genomic, and radiological analyses. Secondary objectives include characterizing the transcriptomic and genomic features of dendritic cells and macrophages, identifying radiomic and circulating tumor DNA (ctDNA) biomarkers, and evaluating their potential as non-invasive tools for recurrence prediction and patient stratification. The study includes a retrospective cohort of approximately 160 patients treated between 2009 and 2023 and a prospective cohort of approximately 50 patients who will be followed for 24 months. Tumor tissue samples, peripheral blood, imaging data (CT/MRI), and clinical information collected during routine care will be analyzed without introducing any experimental interventions or deviations from standard clinical practice. Analyses will include transcriptomic profiling, multiplex spatial characterization of immune cells, circulating tumor DNA sequencing using next-generation sequencing technologies, radiomic feature extraction, and integration of all data using statistical and machine learning approaches. Predictive models will be trained on retrospective data and independently validated in the prospective cohort. The primary endpoint is the prediction of colorectal liver metastasis recurrence within two years after liver resection. Ultimately, the study aims to develop and validate a multimodal predictive model integrating immune, genomic, radiomic, and clinical variables to improve recurrence risk assessment and support personalized patient management. The overall study duration is 36 months. All procedures will be conducted in accordance with ethical standards and data protection regulations, with samples and clinical data pseudonymized and handled in compliance with the GDPR.

Conditions

Colo-rectal Cancer; Liver Metastases; Colon Cancer

Outcome Measures

Primary Outcomes (1)

• Prediction of Colorectal Liver Metastasis Recurrence

  Prediction of colorectal liver metastasis recurrence following curative-intent liver resection using an integrated model based on radiogenomic, immune, and clinical profiling. Recurrence will be assessed through routine clinical follow-up and radiological evaluation.

  24 Months after liver resection

Secondary Outcomes (4)

• Association Between Myeloid Immune Profiles and Clinical Outcomes

  Up to 24 Months after liver resection

• Genomic Alterations Associated With Immune Landscape Patterns

  Baseline (analysis of collected tumour tissue and ctDNA samples)

• Radiomic Features Associated With Immune Cell Distribution

  Baseline (pre-operative MRI/CT imaging)

• Performance of the Machine Learning-Based Recurrence Prediction Model

  Up to 24 Months after liver resection

Study Arms (2)

Retrospective CRLM Cohort

Patients with histologically confirmed colorectal liver metastases who underwent curative-intent liver resection between January 2009 and December 2023 and for whom tumour tissue and clinical data are available. Retrospective collection and analysis of tumour tissue, radiological, genomic, immune and clinical data.

Other: Radiogenomic and Immune Profiling

Prospective CRLM Cohort

Patients with histologically confirmed colorectal liver metastases undergoing standard clinical management and curative-intent liver resection, enrolled prospectively with collection of tumour tissue and peripheral blood samples. Prospective collection and analysis of tumour tissue, peripheral blood-derived ctDNA, radiological, genomic, immune and clinical data.

Other: Prospective Radiogenomic and ctDNA Profiling

Interventions

Prospective Radiogenomic and ctDNA Profiling OTHER

Patients with histologically confirmed colorectal liver metastases undergoing standard clinical management and curative-intent liver resection, enrolled prospectively with collection of tumour tissue and peripheral blood samples. Prospective collection and analysis of tumour tissue, peripheral blood-derived ctDNA, radiological, genomic, immune and clinical data.

Prospective CRLM Cohort

Radiogenomic and Immune Profiling OTHER

Analysis of tumour tissue, radiological images, and clinical data collected during routine clinical care. Molecular, genomic, spatial, transcriptomic, and radiomic profiling will be performed to investigate associations with recurrence risk and clinical outcomes in patients with colorectal liver metastases. No investigational drugs, devices, or experimental procedures are administered as part of the study.

Retrospective CRLM Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with metastatic colorectal cancer and histologically confirmed colorectal liver metastases undergoing standard clinical management and curative-intent liver resection at Fondazione Policlinico Universitario A. Gemelli IRCCS. The study includes both a retrospective cohort with available tumour tissue and clinical data and a prospective cohort undergoing collection of tumour tissue and peripheral blood samples during routine clinical care

You may qualify if:

• Age ≥18 years.
• Histologically confirmed colorectal liver metastases.
• Administration of neoadjuvant chemotherapy prior to liver resection, with objective tumour response classified as partial response (PR) or stable disease (SD) according to RECIST criteria.
• Availability of a hepatobiliary contrast-enhanced MRI performed within 2 months before surgery.
• Provision of informed consent for prospectively enrolled participants, or eligibility under Article 110-bis of the Italian Privacy Code for retrospectively enrolled participants.

You may not qualify if:

• Recurrent metastatic disease.
• Liver resection performed with non-curative intent.
• Current or previous hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Concomitant malignancies or history of another malignancy treated within the previous 5 years.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Biospecimen

Retention: SAMPLES WITH DNA

Genomic profiling will be performed on circulating tumour DNA (ctDNA) extracted from plasma samples collected during routine clinical care. Next-generation sequencing (NGS) approaches and targeted sequencing panels will be used to identify tumour-associated genetic variants. Tumour tissue samples from primary colorectal cancer and colorectal liver metastases will also be collected and analysed for molecular, spatial, and transcriptomic profiling

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Simone Famularo

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simone Famularo, MD

CONTACT

+390630155626; simone.famularo@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiogenomic profiling of dendritic cells and macrophages to predict recurrence in colorectal liver metastasis

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 4, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 4, 2026

Record last verified: 2026-07