Radiogenomic Profiling of Dendritic Cells and Macrophages to Predict Recurrence in Colorectal Liver Metastasis (RaP-DMac-LiMe)
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.
調査の概要
状態
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Simone Famularo, MD
- 電話番号：+390630155626
- メール：simone.famularo@policlinicogemelli.it
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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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.
|
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.
|
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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.
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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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Prediction of Colorectal Liver Metastasis Recurrence
時間枠：24 Months after liver resection
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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.
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24 Months after liver resection
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Genomic Alterations Associated With Immune Landscape Patterns
時間枠：Baseline (analysis of collected tumour tissue and ctDNA samples)
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Identification of tumour-associated genetic alterations correlated with specific immune microenvironment profiles in colorectal liver metastases.
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Baseline (analysis of collected tumour tissue and ctDNA samples)
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Radiomic Features Associated With Immune Cell Distribution
時間枠：Baseline (pre-operative MRI/CT imaging)
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Identification of radiomic features associated with the distribution and characteristics of dendritic cells and tumour-associated macrophages within tumour tissues.
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Baseline (pre-operative MRI/CT imaging)
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Performance of the Machine Learning-Based Recurrence Prediction Model
時間枠：Up to 24 Months after liver resection
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Development and validation of a machine learning-based model for recurrence risk prediction.
Model performance will be assessed using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value.
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Up to 24 Months after liver resection
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Correlation Between Myeloid Immune Cell Frequencies and Clinical Outcome Measures
時間枠：Up to 24 Months after liver resection
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Correlation between dendritic cell and tumor-associated macrophage frequencies (% of CD45⁺ immune cells), measured by multiparametric flow cytometry, and overall survival (months), relapse-free survival (months), and recurrence status (yes/no).
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Up to 24 Months after liver resection
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協力者と研究者
捜査官
- 主任研究者：Simone Famularo、Fondazione Policlinico Universitario Agostino Gemelli IRCCS
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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