Implementation of Fluorescence Imaging Using Indocyanine Green to Identify Sentinel Lymph Nodes During Surgery for Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,760
- 试验地点
- 7
- 主要终点
- Adoption of ICG for sentinel lymph node biopsy (SLNB)
研究概览
简要总结
The goal of this clinical trial is to learn how to successfully introduce a new method for finding the sentinel lymph node during breast cancer surgery into routine hospital care. The method uses a dye called indocyanine green (ICG) and a special camera to see the lymph node. The sentinel lymph node is the first lymph node that cancer is likely to spread to.
In the Netherlands, about 1 in 7 women develops breast cancer. Finding out whether cancer has spread to the lymph nodes is important for planning treatment and predicting outcomes. The current standard method for sentinel lymph node biopsy (SLNB) uses a radioactive tracer called radioisotope technetium-labeled (99mTc)-nanocolloid. While accurate, this method has several drawbacks: it exposes patients to radioactivity, requires an extra hospital visit or travel to another hospital due to limited nuclear medicine facilities, and is not sustainable. Surgeries using 99mTc can only take place on certain days due to logistical issues, and the signal from 99mTc can be disturbed by the tumor marker placed in the breast.
ICG works as well as 99mTc for SLNB and offers several advantages: it is given during surgery (no extra visit needed), produces no radiation, and reduces costs. However, it is still not widely used in the Netherlands because hospitals may not be familiar with it or unsure how to make the switch.
This study will introduce ICG step-by-step in several Dutch hospitals and evaluate how to make the change as smooth and effective as possible. It will take place in three stages: I) SLNB with 99mTc only (current practice); II) SLNB with both 99mTc and ICG (transition phase); III) SLNB with ICG only (full implementation).
All study procedures take place during planned surgery, with no extra hospital visits. After surgery, participants will receive a short questionnaire (10-15 minutes) to share their experiences with the procedure. Their feedback, combined with input from healthcare providers, will help researchers develop a uniform medical protocol, an implementation guide, and educational materials for surgeons and surgical trainees.
The aim is to make ICG widely available across the Netherlands, ensuring that care is less burdensome, more sustainable, and more cost-effective, while keeping treatment accessible in local hospitals.
详细描述
Background:
Breast cancer affects one in seven women. Detecting lymph node metastases via the sentinel lymph node biopsy (SLNB) is crucial for prognosis and treatment. The gold standard is radio-guided surgery using the radioisotope technetium-labeled (99mTc)-nanocolloid, which requires preoperative injection and lymphoscintigraphy. However, the use of 99mTc poses significant burdens on patients, as it requires additional hospital visits or travel to another hospital due to the limited availability of nuclear medicine facilities. The use of 99mTc also creates logistical challenges and lacks sustainability. A recently proven, equally effective and safe alternative method is peroperative real-time fluorescence imaging using Indocyanine Green (ICG). ICG offers many advantages over 99mTc for patients, healthcare providers, and society. Yet, the use of ICG for SLNB remains limited, as hospitals face challenges due to uncertainty in transitioning and limited familiarity with recent findings. Implementation guidance is imperative for effective adoption, to avert further practice variation and to ensure patients benefit from this evidence-based alternative method.
Objectives:
The INFINITE trial aims to successfully implement ICG-fluorescence for identifying the sentinel lymph node by guiding the implementation process using the Effective Implementation of Change model developed by Grol and Wensing, identifying and understanding the factors influencing implementation outcomes through the Consolidated Framework for Implementation Research, evaluating the outcomes of implementation efforts using a mixed-methods approach and the outcomes framework proposed by Proctor et al., and creating conditions for nationwide implementation. Secondary aims are to develop a uniform medical protocol for the use of ICG for SLNB, to develop an implementation guide that aligns with current practice, to prepare educational materials for surgeons and modules for the curriculum of surgical residents (CASH), to produce patient information materials and organize interactive meetings for surgical healthcare providers and their teams, to further substantiate the effectiveness, safety, and cost-effectiveness of ICG, to increase support and a sense of urgency for ICG implementation by organizing informational sessions during annual conferences of the relevant scientific associations, and to facilitate nationwide scale-up by incorporating ICG into SLNB guidelines.
Study Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 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
- •Patients ≥ 18 years old.
- •DCIS or invasive breast cancer, confirmed by biopsy
- •Clinically node-negative, confirmed by preoperative axillary ultrasound
- •Indication for breast cancer surgery with SLN procedure via axillar incision
排除标准
- •Combined MARI procedure
- •Known allergy for Indocyanine Green (ICG), intravenous contrast or iodine
- •History of axillary lymph node dissection
- •Hyperthyroidism or thyroid cancer
- •Pregnancy or breast-feeding
- •No written informed consent according to ICH/GCP and national regulations.
研究组 & 干预措施
Transition phase (99mTc + ICG)
Participants receive preoperative injection of radioisotope technetium-labeled (99mTc)-nanocolloid and preoperative lymphoscintigraphy (without marking the location on the skin). Surgeons are blinded to preoperative lymphoscintigraphy results. After induction of general anesthesia, indocyanine green (ICG) is injected periareolar. Surgery is primarily guided by ICG fluorescence imaging to identify and remove the sentinel lymph node(s). Excised lymph nodes are then checked for 99mTc activity using a gamma-detection probe as a control. This phase is designed to allow surgeons to gain experience with the ICG technique while maintaining safety through parallel use of the established 99mTc method.
干预措施: Sentinel lymph node biopsy (Procedure)
Pre-implementation (99mTc only)
Participants undergo sentinel lymph node biopsy (SLNB) using the current standard of care: injection of radioisotope technetium-labeled (99mTc)-nanocolloid and preoperative lymphoscintigraphy, followed by radio-guided surgery with a gamma-detection probe.
干预措施: Sentinel lymph node biopsy (Procedure)
Post-implementation (ICG only)
Participants undergo SLNB using ICG only. ICG is injected periareolar after induction of general anesthesia and visualized intraoperatively with a fluorescence camera to guide excision of the sentinel lymph node(s).
干预措施: Sentinel lymph node biopsy (Procedure)
Pre-implementation (99mTc only)
Participants undergo sentinel lymph node biopsy (SLNB) using the current standard of care: injection of radioisotope technetium-labeled (99mTc)-nanocolloid and preoperative lymphoscintigraphy, followed by radio-guided surgery with a gamma-detection probe.
干预措施: Technetium (99mTc) (Drug)
Pre-implementation (99mTc only)
Participants undergo sentinel lymph node biopsy (SLNB) using the current standard of care: injection of radioisotope technetium-labeled (99mTc)-nanocolloid and preoperative lymphoscintigraphy, followed by radio-guided surgery with a gamma-detection probe.
干预措施: Indocyanine Green (Drug)
Transition phase (99mTc + ICG)
Participants receive preoperative injection of radioisotope technetium-labeled (99mTc)-nanocolloid and preoperative lymphoscintigraphy (without marking the location on the skin). Surgeons are blinded to preoperative lymphoscintigraphy results. After induction of general anesthesia, indocyanine green (ICG) is injected periareolar. Surgery is primarily guided by ICG fluorescence imaging to identify and remove the sentinel lymph node(s). Excised lymph nodes are then checked for 99mTc activity using a gamma-detection probe as a control. This phase is designed to allow surgeons to gain experience with the ICG technique while maintaining safety through parallel use of the established 99mTc method.
干预措施: Indocyanine Green (Drug)
Post-implementation (ICG only)
Participants undergo SLNB using ICG only. ICG is injected periareolar after induction of general anesthesia and visualized intraoperatively with a fluorescence camera to guide excision of the sentinel lymph node(s).
干预措施: Technetium (99mTc) (Drug)
结局指标
主要结局
Adoption of ICG for sentinel lymph node biopsy (SLNB)
时间窗: During Phase III, the post-implementation period, which is the final 9 months for hospitals in cluster 1, final 6 months for cluster 2, and final 3 months for cluster 3, within the 18-month trial.
Proportion of SLNB procedures performed using indocyanine green (ICG) only, compared to the total number of SLNB procedures perfomed, using any tracer, on the target population in the observational cohort of phase III. Adoption will be assessed using hospital administrative data, with cross-checking against the prospective screening and inclusion log.
次要结局
- Fidelity of ICG-fluorescence implementation(Phase III; intraoperative survey completed immediately after each SLNB procedure.)
- Tracer Concordance of SLNs(Intraoperative survey completed immediately after each SLNB procedure during Phase II only.)
- Paired per-case detection rate of SLNs by ICG versus 99mTc(Intraoperative survey completed immediately after each SLNB procedure during Phase II only.)
- Direct in-hospital per-patient costs per SLNB ICG compared to 99mTc(Conducted in parallel with the current study. The cost overview is based on cost drivers associated with each surgical pathway, as identified from the literature and clinical experience.)
- National budget impact of ICG-fluorescence implementation(Conducted in parallel with the current study. The BIA covers the period of 2025-2029.)
- Patient-level costs for SLNB using 99mTc or ICG-fluorescence(Patient survey administered within 1 week after surgery during Phase I (99mTc) and Phase III (ICG).)
- Fidelity of ICG-fluorescence implementation(Phase III; intraoperative survey completed immediately after each SLNB procedure.)
- Total number of lymph nodes removed, SLNs, and non-SLNs(Intraoperative survey completed immediately after each SLNB procedure across all study phases (from study start up to 18 months).)
- Appropriateness of ICG-fluorescence(A questionnaire is administered to healthcare providers in each participating hospital during the 3rd month of Phase III, corresponding to month 12 for cluster 1, month 15 for cluster 2, and month 18 for cluster 3.)
- Feasibility of ICG-fluorescence implementation(A questionnaire is administered to healthcare providers in each participating hospital during the 3rd month of Phase III, corresponding to month 12 for cluster 1, month 15 for cluster 2, and month 18 for cluster 3.)
- Acceptability of ICG-fluorescence implementation(A questionnaire is administered to healthcare providers in each participating hospital during the 3rd month of Phase III, corresponding to month 12 for cluster 1, month 15 for cluster 2, and month 18 for cluster 3.)
- Patient satisfaction with SLNB procedure(Questionnaire administered within 1 week after surgery during all phases of the trial (from study start up to 18 months).)
- Per-node detection of SLNs by tracer(Intraoperative survey completed immediately after each SLNB procedure across all study phases (from study start up to 18 months).)
- Patient-level costs for SLNB using 99mTc or ICG-fluorescence(Patient survey administered within 1 week after surgery during Phase I (99mTc) and Phase III (ICG).)
- Tracer Concordance of SLNs(Intraoperative survey completed immediately after each SLNB procedure during Phase II only.)
- National budget impact of ICG-fluorescence implementation(Conducted in parallel with the current study. The BIA covers the period of 2025-2029.)
- Per-case identification rate of SLNs by tracer(Intraoperative survey completed immediately after each SLNB procedure across all study phases (from study start up to 18 months).)
- Detection time to first, second and/or third (sentinel) lymph node(Intraoperative survey completed immediately after each SLNB procedure across all study phases (from study start up to 18 months).)
- Total SLNB procedure duration(Intraoperative survey completed immediately after each SLNB procedure across all study phases (from study start up to 18 months).)
- Paired per-case detection rate of SLNs by ICG versus 99mTc(Intraoperative survey completed immediately after each SLNB procedure during Phase II only.)
- Pathology of SLNs(Data collected from the pathology report within 2-3 weeks after surgery, across all study phases (from study start up to 18 months).)
- Safety of ICG-fluorescence for SLNB(Events are systematically recorded using a standardized postoperative case report form in REDCap, completed within 3 to 4 weeks after surgery in all study phases (from study start up to 18 months).)
- Direct in-hospital per-patient costs per SLNB ICG compared to 99mTc(Conducted in parallel with the current study. The cost overview is based on cost drivers associated with each surgical pathway, as identified from the literature and clinical experience.)
研究者
Isabelle Henskens
Coordinating investigator
St. Antonius Hospital