A Randomized Controlled Comparison Study of Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer
试验速览
- 阶段
- 不适用
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- Overall SLN detection rate
研究概览
简要总结
The metastasis rate of pelvic lymph node in early cervical cancer is low. Systemic lymph node resection is traumatic and has many complications. Sentinel lymph node (SLN) biopsy can effectively avoid unnecessary lymph node dissection, which has been recommended in clinical guidelines. Indocyanine green(ICG) fluorescence imaging as the method of SLN mapping is recommended in international guidelines. However, the imaging equipment is very expensive which limits the popularization of ICG in different medical centers of various surgical volumes. Carbon nanoparticle is an innovative tracer without any special imaging equipment for SLN mapping in China. Some retrospective researches have proved that carbon nanoparticle is effective, simple, economic and suitable for popularization in different medical centers. In this study, a prospective randomized controlled trial will be conducted to analyze the non-inferiority of carbon nanoparticles compared to ICG, and to verify the application value of carbon nanoparticles. 144 cervical cancer patients with stage IB1 (FIGO2018) will be prospectively enrolled and randomly divided into two groups (R = 1:1). 72 patients will undergo SLN biopsy with carbon nanoparticles and 72 patients will be mapped by ICG. The primary endpoint is overall SLN detection rate. The secondary endpoints include bilateral SLN detection rate, the number of SLN detected, sensitivity, false negative rate and negative predictive value of SLN biopsy. Diagnostic accuracy will be evaluated at both pelvis and patient levels. What's more, SLN pathological ultrastaging will be conducted to increase the diagnostic accuracy. The hypothesis of this study is that the overall SLN detection rate by carbon nanoparticles is not inferior to that using ICG. And the differences of bilateral SLN detection rate, sensitivity, false negative rate and negative predictive value between two groups are not significant.
详细描述
This is a prospective randomized controlled non-inferiority trial. Patients with early stage cervical cancer who met the inclusion criteria are divided into carbon nanoparticle group and ICG group by block random method. It is assumed that the overall SLN detection rate was PT (90%) in experimental group(carbon nanoparticle) and was PC (85%) in control group (ICG). The non-inferiority threshold Δ is -10%. The type I error and type II error of the hypothesis test are set as 0.05 and 0.2 respectively. The sample size is 60 cases in each group calculated by"Non inferiority tests for two proportions"method of Power Analysis and Sample Size (PASS) Software 11.0. After calculation, considering the 20% shedding rate, the sample size is 144 totally. There are 72 cases in experimental group and 72 cases in control group. Radical hysterectomy and systemic pelvic lymph node dissection are conducted after SLN resection, and paraaortic lymph node biopsy is conducted when necessary. Sentinel lymph nodes will be cut at 2-mm intervals perpendicular to the long axis in a bread-loaf fashion. Sentinel lymph nodes are then fixed in formalin and embedded in paraffin. Routine hemotoxin & eosin(H&E) staining is used for each SLN. Subsequent ultrastaging is performed if the initial H&E assessment is negative. SLN ultrastaging is performed by cutting three 5-μm sections at two levels, 50-μm apart, from each paraffin block of negative SLN. At the first level, two adjacent 5-μm sections are stained with H&E and immuno-histochemistry using the anti-cytokeratin AE1:AE3, respectively. At the second level, one 5-μm section is evaluated by H&E staining. Nonsentinel lymph nodes are bisected parallel to the long axis and stained with H&E staining.Nodal metastases are classified as (1) isolated tumor cells (ITCs) (single cells or clusters ≤ 0.2mm in largest dimension),(2) micrometastases (tumor deposits 0.2mm-2 mm), or (3) macrometastases (tumor deposits > 2mm). All pathological reviews will be finished by two independent gynecologic pathologists in the Department of Pathology of Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College. A third senior pathologist is invited to decide the diagnosis when discordance occurs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Cervical squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma diagnosed by pathological biopsy;
- •Tumor stage is IB1 (FIGO 2018);
- •No distant metastasis (chest, abdominal and pelvic enhanced CT or positron emission tomography (PET) -CT);
- •18-70 years old;
- •Eastern Cooperative Oncology Group (ECOG) score ≤ 2 and tolerable for radical hysterectomy and systemic lymph node resection;
- •No obvious dysfunction or chronic disease of heart, liver and kidney, and no history of other malignant tumors;
- •Volunteer to participate in the study and sign the informed consent.
排除标准
- •Residual cervical cancer;
- •Small cell carcinoma, neuroendocrine carcinoma and other special histological types;
- •Patients who have received radiotherapy or chemotherapy before enrollment;
- •Allergic constitution, allergic to iodine;
- •ICG skin test is positive;
- •Patients considered unsuitable for inclusion by the researchers.
结局指标
主要结局
Overall SLN detection rate
时间窗: From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.
The percentage of patients with successfully detected SLNs in all eligible patients.
次要结局
- False negative rate(From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.)
- Negative predictive value(From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.)
- Bilateral SLN detection rate(From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.)
- The number of detected SLNs(From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.)
- Location of SLNs(From date of operation to the date of completion of routine pathological examination, usually 2 weeks after operation.)
- Sensitivity of SLN biopsy(From date of operation to the date of completion of SLNs pathological ultrastaging. 3 years.)