Liquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,200
- 试验地点
- 4
- 主要终点
- Sensitivity
研究概览
简要总结
This is an multicenter study that will test the diagnostic accuracy of a blood test (i.e., a liquid biopsy) for the diagnosis of colorectal cancer (CRC), advanced adenomas (AAs), as well as Lynch-syndrome associated cancers. Additionally, a pre-planned analysis will evaluate the use of this liquid biopsy as a tool for molecular residual disease monitoring purposes.
详细描述
Colorectal cancer (CRC) remains a significant public health burden as the third-most commonly diagnosed and second-deadliest malignancy. While CRC is potentially preventable through the removal of precursor lesions known as advanced adenomas (AAs), current screening modalities have limitations. The fecal immunochemical test (FIT) exhibits reduced sensitivity for early-stage CRC and AAs, primarily lowering mortality rather than incidence. Colonoscopy, while effective, is invasive, costly, and suffers from suboptimal adherence. Additionally, individuals with Lynch syndrome (LS), who carry a pathogenic germline variant in mismatch repair (MMR) genes, lack effective and reliable methods for early-stage detection of non-CRC tumors associated with the syndrome.
The rationale of this study, BEACON/2026, is to develop and validate two blood-based tests to address these clinical gaps. The first is a screening test sensitive to both CRC and AAs to complement existing screening options; the second is a multi-cancer early detection (MCED) test tailored to the LS spectrum. The central hypothesis is that a liquid biopsy approach combining cell-free microRNAs (cf-miRNAs, which are sensitive) and exosome-bound microRNAs (exo-miRNAs, which are specific) can effectively distinguish patients with AAs, CRC, and LS-associated cancers from controls.
This study follows the Early Detection Research Network (EDRN) recommendations for biomarker development, including biomarker discovery, prioritization, training, and independent validation (Phases I through III). The experimental design complies with PROBE recommendations for prospectively collected biospecimens that are blindly evaluated. The procedure involves the collection of peripheral blood to isolate RNA from plasma or serum for reverse transcription, quantitative polymerase chain reaction (RT-qPCR) analysis and machine-learning modeling . This non-invasive approach aims to provide a cost-effective, patient-friendly alternative to improve screening participation and disease monitoring
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All individuals included in the study need to have had a colonoscopy at the time of blood sampling.
- •Received standard diagnostic and staging (as necessary) procedures as per local guidelines, and at least one sample was drawn before receiving any curative-intent treatment.
- •Received standard pathological and endoscopic diagnosis and assessment for cohort assignment
排除标准
- •Lack of informed consent
- •Inflammatory bowel disease
研究组 & 干预措施
Lynch syndrome, without Lynch-syndrome associated cancers
Individuals with Lynch syndrome, who are free of Lynch-syndrome associated cancers at the time of blood drawing
干预措施: BEACON (Diagnostic Test)
Lynch syndrome, with Lynch-syndrome associated cancers
Individuals with Lynch syndrome, who have one (or more) Lynch-syndrome associated cancer(s) at the time of blood drawing
干预措施: BEACON (Diagnostic Test)
Colorectal cancer
Individuals with sporadic biopsy-proven colorectal cancer, as identified during routine colonoscopy and diagnosed via pathological review
干预措施: BEACON (Diagnostic Test)
Advanced adenoma
Individuals with sporadic advanced adenomas, defined as (i) more than 3 colorectal polyps, (ii) presence of high-grade dysplasia in one or more polyp, or (iii) polyp(s) >10 mm
干预措施: BEACON (Diagnostic Test)
Colonoscopy-negative controls
Individuals whose colonoscopy was negative for colorectal cancer and for advanced colorectal adenomas
干预措施: BEACON (Diagnostic Test)
Pre-treatment samples
Individuals with (i) colorectal cancer, or (ii) advanced adenomas, or (iii) Lynch syndrome associated cancer(s) will have the possibility to participate to a sub-analysis of this study, where their circulating plasma levels of biomarkers will be evaluated prior to resection (treatment-naive) and post-resection (to measure the molecular persistence of the disease after the resection)
干预措施: BEACON (Diagnostic Test)
Post-treatment samples
Individuals with (i) colorectal cancer, or (ii) advanced adenomas, or (iii) Lynch syndrome associated cancer(s) will have the possibility to participate to a sub-analysis of this study, where their circulating plasma levels of biomarkers will be evaluated prior to resection (treatment-naive) and post-resection (to measure the molecular persistence of the disease after the resection)
干预措施: BEACON (Diagnostic Test)
结局指标
主要结局
Sensitivity
时间窗: Through study completion, an average of 1 year
True positive rate: the probability of a positive test result, conditioned on the individual truly being positive
次要结局
- Specificity(Through study completion, an average of 1 year)
- Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy)(Through study completion, an average of 1 year)