Colorectal Cancer
Conditions
Keywords
Oligometastatic Colorectal Cancer, Plasma Multi - omics Detection, ctDNA, cfRNA, Proteomics, Metabolomics, Conversion Therapy
Brief summary
This prospective study (PMEIRR-OCCCT) evaluates the utility of plasma multi-omics-including circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), proteomics, and metabolomics-in assessing response to conversion therapy and predicting recurrence in 120 patients with oligometastatic colorectal cancer (≤5 liver and/or lung metastases). Blood samples are collected at predefined timepoints: before conversion therapy, 3-6 weeks post-therapy, within 2 months after surgery or non-radical treatment, and during 24-month follow-up. Patients are stratified into radical vs. non-radical treatment groups based on post-conversion resectability. Tumor assessments (CT/MRI and CEA/CA19-9) occur every 3-4 months. The primary endpoint is progression-free survival (PFS) stratified by MRD status (ctDNA-negative vs. ctDNA-positive). Secondary endpoints include objective response rate (ORR), overall survival (OS), and duration of no evidence of disease (NED). The study aims to identify multi-omic biomarkers for early recurrence prediction and personalized intervention.
Interventions
DRUGPlasma Multi - omics Detection
Description: This study utilizes a holistic plasma multi-omics approach, integrating circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), proteomics, and metabolomics to evaluate treatment response. Unlike conventional single-marker studies, this integration captures diverse biological signals-from genomic alterations to metabolic shifts-providing a superior assessment of efficacy and recurrence risk in oligometastatic CRC. All participants, regardless of their subsequent treatment path (radical or non-radical), undergo standardized blood collection at key clinical milestones: baseline, post-conversion therapy, and throughout a 2-year follow-up period. This allows for a continuous molecular "snapshot" of the disease, enabling the identification of MRD-positive patients who may require intensified intervention.
Sponsors
Xiujuan Qu
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed oligometastatic colorectal cancer with ≤5 liver and/or lung metastases. * Assessed as potentially resectable by multidisciplinary team (MDT) and planned for neoadjuvant conversion therapy. * Age 18-75 years. * Estimated survival ≥6 months. * Willingness to provide blood samples and undergo long-term follow-up. * Signed informed consent.
Exclusion criteria
* Pregnant or breastfeeding individuals. * Uncontrolled medical conditions that could interfere with study assessments. * Significant cardiac, neurological, or other severe comorbidities. * History of other malignancies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) in MRD-Negative and MRD-Positive Groups | From treatment initiation through 24 months, with assessments at each follow-up visit every 3-4 months. | The primary outcome is progression-free survival (PFS), stratified by minimal residual disease (MRD) status. PFS is defined as the time from treatment initiation to the first occurrence of tumor recurrence, disease progression, or death from any cause, whichever occurs first. Tumor assessments are performed every 3-4 months for up to 24 months using imaging (CT or MRI) and serum tumor markers (CEA and CA19-9). Blood samples are collected at predefined time points to determine MRD status via ctDNA analysis, which informs individualized treatment decisions. Differences in PFS between MRD-negative and MRD-positive groups are evaluated using the Kaplan-Meier method and log-rank test, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated using Cox proportional hazards regression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Assessed at the first tumor evaluation visit, 8 weeks after treatment initiation. | Proportion of patients with tumor volume reduction ≥30% and maintained for ≥4 weeks, including complete response (CR) and partial response (PR). |
| Overall Survival (OS) | Monitored continuously from treatment initiation through 24 months, with survival status updated every 3-4 months. | Time from treatment initiation to death from any cause. |
| Disease-Free State (NED) | Evaluated at each follow-up visit during the 24-month period. | Absence of detectable tumor via imaging and clinical examination after treatment. |
| ctDNA and cfRNA Dynamic Changes | Measured via NGS sequencing at predefined time points: before conversion therapy, 3-6 weeks after conversion therapy, within 2 months after surgery or non-radical treatment, and during follow-up. | Longitudinal changes in ctDNA and cfRNA levels in blood samples collected at multiple time points. |
Countries
China
Outcome results
None listed