Fluorescence imaging using indocyanine green to identify sentinel lymph nodes during surgery for breast cancer (INFINITE): protocol for a hybrid effectiveness-implementation trial using a stepped-wedge cluster design

Introduction: Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in clinically node-negative breast cancer. Traditionally, SLNB is performed using technetium-labelled (^99mTc) nanocolloid, with or without blue dye. However, both tracers have important limitations. Blue dye poses safety risks, while ^99mTc-nanocolloid introduces additional hospital visits, radiation exposure, logistical complexity and high costs. Indocyanine green (ICG) fluorescence is a non-radioactive alternative, offering real-time visualisation while addressing many limitations of traditional tracers. Yet, adoption of ICG-guided SLNB remains limited. This trial aims to guide the implementation of ICG-guided SLNB via axillary incision, evaluate its real-world effectiveness and inform conditions for nationwide scale-up. Methods and analysis: The INFINITE trial is a multicentre, hybrid effectiveness-implementation study employing a stepped-wedge cluster design across seven Dutch hospitals. Clusters sequentially transition from SLNB using ^99mTc-nanocolloid alone (Phase I) to ICG as the primary tracer and ^99mTc-nanocolloid as a within-patient control (Phase II), and finally to ICG alone (Phase III). The hybrid design enables evaluation of implementation outcomes (penetration, adoption, fidelity, appropriateness, feasibility, acceptability), intervention outcomes (effectiveness, safety, costs) and patient-reported experience (patient satisfaction). The primary outcome is penetration, the proportion of Phase III SLNB procedures performed with ICG alone. An integrated implementation approach combines the Grol and Wensing model (process model), the Consolidated Framework for Implementation Research (determinant framework) and Proctor’s outcomes framework (evaluation framework). Outcomes are assessed quantitatively, supplemented by an embedded mixed-methods component to explain variation in implementation across centres. Ethics and dissemination: Ethical approval was obtained from the Medical Research Ethics Committees United (6 November 2024; NL87551.100.24). Results will be submitted to open-access, peer-reviewed journals and presented at conferences focused on oncological or image-guided surgery. Implementation tools, including a clinical protocol, implementation guide, educational materials and patient information, will be developed to support national adoption. Trial registration number: NCT07146295.