A Prospective Multi-center Cohort Study Based on Deep Learning-based cfDNA Fragment Omics to Verify the TuFEst Model for Axillary Lymph Node Status Assessment in Breast Cancer Patients Undergoing Primary Surgery or Neoadjuvant Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Pathological axillary lymph node positivity rate among TuFEst-LN-negative patients
研究概览
简要总结
Through the research of this project, we expect to validate the clinical utility of the TuFEst-LN model in assessing axillary lymph node status in breast cancer patients. Specifically, we aim to prospectively validate its ability to identify pathologically node-negative patients among clinically and radiologically assessed cN0 patients undergoing upfront surgery ，and explore the predictive value of the TuFEst-LN model combined with preoperative MRI for ypN status assessment in initially node-positive patients following neoadjuvant therapy.
详细描述
Through the research of this project, we aim to prospectively validate the locked TuFEst-LN model, a cfDNA fragmentomics-based liquid biopsy model, for axillary lymph node status assessment in patients with breast cancer. This study will evaluate the ability of the TuFEst-LN model to identify pathologically node-negative patients among clinically and radiologically assessed cN0 patients with cT1-3 invasive breast cancer undergoing upfront surgery without neoadjuvant therapy. In addition, this study will explore the predictive value of the TuFEst-LN model combined with preoperative magnetic resonance imaging (MRI) for post-neoadjuvant pathological axillary lymph node status (ypN) in initially node-positive breast cancer patients. Peripheral blood samples and clinical data will be prospectively collected from multiple centers, and model predictions will be compared with final surgical pathology as the reference standard. This study aims to validate the clinical utility of cfDNA fragmentomics-based liquid biopsy for noninvasive axillary lymph node assessment and provide evidence for individualized axillary management in breast cancer.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Cohort 1-Specific Inclusion Criteria
- •Participants in Cohort 1 must meet all of the following criteria:
- •Histologically confirmed invasive breast cancer.
- •Clinical stage cT1-3, cN0, M0 disease at enrollment.
- •No clinically palpable suspicious metastatic axillary lymph nodes identified by physical examination.
- •No radiologically suspicious metastatic axillary lymph nodes identified by preoperative axillary imaging (at least ultrasound examination). Patients with suspicious lymph nodes must have negative cytological or histological findings confirmed by fine-needle aspiration or core needle biopsy.
- •No prior neoadjuvant therapy, including chemotherapy, targeted therapy, immunotherapy, endocrine therapy, or breast/axillary radiotherapy before enrollment.
- •Planned to undergo definitive breast surgery with sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND).
- •Ability to provide qualified preoperative plasma samples for cfDNA analysis.
- •Cohort 2-Specific Inclusion Criteria
- •Participants in Cohort 2 must meet all of the following criteria:
- •Histologically confirmed invasive breast cancer.
- •Ipsilateral axillary lymph node metastasis confirmed by fine-needle aspiration or core needle biopsy at initial diagnosis.
- •No evidence of distant metastasis (M0), and planned to receive standard neoadjuvant systemic therapy followed by definitive breast and axillary surgery.
- •Completion of the planned neoadjuvant therapy, or premature discontinuation due to clinical reasons while remaining eligible for subsequent surgery.
- •Ability to provide a baseline plasma sample (T0) within 24-72 hours before initiation of the first systemic treatment (including chemotherapy, immunotherapy, or targeted therapy).
- •Availability of preoperative breast and axillary magnetic resonance imaging (MRI) after completion of neoadjuvant therapy. Patients unable to undergo MRI due to contraindications or other reasons may be included in the cfDNA-only analysis set but will not be included in the complete-case analysis of the combined cfDNA-MRI model.
- •Ability to provide a second plasma sample (T1) within 24-72 hours before surgery after completion of neoadjuvant therapy. Patients without T0 samples may still be included in the exploratory analysis of T1 cfDNA combined with MRI for ypN prediction.
- •Availability of complete postoperative breast and axillary pathological evaluation results.
排除标准
- •Participants meeting any of the following criteria will be excluded:
- •Pregnancy or breastfeeding.
- •Prior surgical removal of the primary breast lesion before enrollment, resulting in inability to obtain the required preoperative blood samples.
- •Presence of confirmed distant metastasis.
- •Presence of supraclavicular, internal mammary, or other lymph node lesions that cannot be adequately assessed by planned surgery and pathological evaluation.
- •History of another active malignancy within the previous 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, or other malignancies considered by investigators unlikely to affect study outcomes.
- •Receipt of whole blood, plasma, or other blood product transfusion within 30 days prior to enrollment.
- •Insufficient plasma sample volume, severe hemolysis, or failure to meet cfDNA sequencing quality control requirements determined by the central laboratory.
- •Absence of evaluable axillary surgical pathological results.
- •Any other condition considered by the investigator to make the patient unsuitable for participation in this study.
研究组 & 干预措施
1
Invasive breast cancer patients with cT1-3N0M0 disease who have received no prior neoadjuvant therapy or radiotherapy and undergo SLNB and/or ALND for axillary evaluation. A total of 300 participants are planned to be enrolled in Cohort 1
干预措施: No Intervention: Observational Cohort (Other)
2
Patients with newly diagnosed invasive breast cancer and biopsy-confirmed axillary lymph node metastasis without distant metastasis, who are scheduled to receive standard neoadjuvant systemic therapy followed by breast and axillary surgery . Patients who complete or prematurely discontinue neoadjuvant therapy for clinical reasons but proceed to surgery are eligible.At least 100 participants are planned to be enrolled in Cohort 2.
干预措施: No Intervention: Observational Cohort (Other)
结局指标
主要结局
Pathological axillary lymph node positivity rate among TuFEst-LN-negative patients
时间窗: up to 2 weeks
Defined as the proportion of patients with pathological axillary lymph node positivity (pN1mi or higher) among patients predicted as negative by the locked TuFEst-LN model in Cohort 1. FOR = FN/(TN+FN) = 1-NPV.
Negative predictive value (NPV) of the TuFEst-based classifier for predicting pathologic node-negative status (pN0)
时间窗: up to 2 weeks
Validate the accuracy of the TuFEst model in predicting breast cancer lesion and lymph node tumor burden status among patients with primary breast cancer and those undergoing neoadjuvant therapy.
次要结局
- Negative Predictive Value (NPV) of the TuFEst-LN Model(2 weeks)
- Sensitivity and False Negative Rate (FNR) for Detecting Pathological Axillary Lymph Node Positivity(2 weeks)
- Specificity of the TuFEst-LN Model(2 weeks)
- Positive Predictive Value (PPV), Overall Accuracy, and Discrimination Performance(2 weeks)
- Proportion of Patients Classified as Negative by the TuFEst-LN Model(2 weeks)
- Calibration and Net Clinical Benefit of the TuFEst-LN Model(2 weeks)
- Pathological Burden of Missed Positive Cases(2 weeks)