Impact of Neoadjuvant Chemoradiotherapy Versus Surgery Alone on Circulating Tumor Cells in Patients With Stage II-III Rectal Cancer and Negative Circumferential Resection Margin: a Multicenter Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 7
- 主要终点
- Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - shape
研究概览
简要总结
This prospective, multi-centre, randomised clinical trial aims to compare the effect of neoadjuvant chemoradiotherapy versus primary surgery on circulating tumor cells (CTCs) in patients with stage II-III rectal cancer without circumferential resection mar-gin involvement. CTCs are considered a promising biomarker for disease dissemination and treatment response. Patients will be randomized to either primary surgical resection with total mesorectal excision or long-course neoadjuvant chemoradiotherapy followed by surgery. Serial blood samples will be collected at predefined time points to assess the presence and dynamics of CTCs. Secondary endpoints include perioperative morbidity and mortality, local recurrence rate, disease-free survival, and overall survival. The results of this study may provide new insights into the prognostic role of CTCs and contribute to optimising treatment strategies for rectal cancer.
详细描述
Colorectal cancer remains one of the most common malignancies worldwide, and rectal cancer requires a multidisciplinary treatment approach. For patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection has been widely used to reduce the risk of local recurrence. However, the indication for nCRT in patients without circumferential resection margin (CRM) involvement remains controversial. While some studies have suggested benefits of nCRT, others have shown comparable oncological outcomes with primary surgery when high-quality total mesorectal excision (TME) is performed.
Circulating tumor cells (CTCs) are malignant cells detectable in peripheral blood that have been associated with metastatic potential and poor prognosis in various cancers, including colorectal cancer. Monitoring the presence and dynamics of CTCs offers a minimally invasive "liquid biopsy" approach that may provide prognostic information and reflect treatment efficacy. Existing evidence suggests that changes in CTC levels after surgery or systemic therapy may correlate with recurrence risk and survival, but relevant data in rectal cancer patients undergoing multimodal treatment are limited.
This prospective, multi-centre, randomised clinical trial will enrol patients with stage II-III rectal cancer without evidence of CRM involvement on staging magnetic resonance imaging (MRI). Eligible patients will be randomized into two study arms:
- Primary surgery arm: radical surgical resection with total mesorectal excision (TME).
- Neoadjuvant therapy arm: long-course neoadjuvant chemoradiotherapy fol-lowed by delayed surgical resection.
Peripheral blood samples will be collected at predefined time points in both groups to determine the presence and quantity of CTCs. The primary objective is to compare the effect of neoadjuvant chemoradiotherapy versus surgery alone on CTC dynamics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Histologically confirmed rectal adenocarcinoma within 12 cm from anal verge
- •Stage II (cT3-4 N0 M0) or stage III (cT1-4 N1-2, M0)
- •Negative circumferential resection margin on staging MRI
- •ASA physical status I-III
- •Signed informed consent
排除标准
- •Tumor infiltration beyond fascia recti propria on MRI
- •Metastatic disease (stage IV)
- •Recurrent rectal cancer
- •Other concurrent malignancies
- •Emergency surgery required
- •Contraindication to surgery under general anesthesia
结局指标
主要结局
Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - shape
时间窗: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CTC round shape will be observed.
Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - size
时间窗: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The CTC size will be observed, with the border value of \> 4 μm.
Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - DAPI positivity
时间窗: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The DAPI positivity will be observed. A DAPI-positive nucleus is a cell nucleus that has been stained with DAPI (4',6-diamidino-2-phenylindole), a fluorescent dye that binds specifically to the adenine-thymine (A-T) rich regions of double-stranded DNA.
Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - pancytokeratin and/or EpCAM positivity
时间窗: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of pancytokeratin and/or EpCAM positivity in CTCs will be observed. EpCAM positivity refers to the presence of EpCAM (Epithelial Cell Adhesion Molecule) protein on cells, which is a marker primarily expressed on epithelial cells and in many carcinomas.
Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - CD45 negativity
时间窗: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CD45 negativity in CTCs will be observed. "CD45 negative" means a cell does not express the CD45 protein on its surface.
Circulating Tumor Cells (CTC) Dynamics - primary surgery - shape
时间窗: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CTC round shape will be observed.
Circulating Tumor Cells (CTC) Dynamics - primary surgery - size
时间窗: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The CTC size will be observed, with the border value of \> 4 μm.
Circulating Tumor Cells (CTC) Dynamics - primary surgery - DAPI positivity
时间窗: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The DAPI positivity will be observed. A DAPI-positive nucleus is a cell nucleus that has been stained with DAPI (4',6-diamidino-2-phenylindole), a fluorescent dye that binds specifically to the adenine-thymine (A-T) rich regions of double-stranded DNA.
Circulating Tumor Cells (CTC) Dynamics - primary surgery - pancytokeratin and/or EpCAM positivity
时间窗: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of pancytokeratin and/or EpCAM positivity in CTCs will be observed. EpCAM positivity refers to the presence of EpCAM (Epithelial Cell Adhesion Molecule) protein on cells, which is a marker primarily expressed on epithelial cells and in many carcinomas.
Circulating Tumor Cells (CTC) Dynamics - primary surgery - CD45 negativity
时间窗: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively
The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CD45 negativity in CTCs will be observed. "CD45 negative" means a cell does not express the CD45 protein on its surface.
次要结局
- Short-term postoperative outcomes - preoperative complications(Within 30 days after surgery)
- Short-term postoperative outcomes - 30-day morbidity(Within 30 days after surgery)
- Short-term postoperative outcomes - 30-day mortality(Within 30 days after surgery)
- Local recurrence rate(Up to 5 years)
- Disease-free survival (DFS)(3 and 5 years after surgery)
- Overall survival (OS)(3 and 5 years after surgery)