Implementation of fluorescent imaging using indocyanine green to identify sentinel lymph nodes during surgery for breast cancer.

Breast cancer affects one in seven women. Detecting lymph node metastases via
the sentinel lymph node (SLN) procedure is crucial for prognosis and treatment.
The gold standard is a radio-guided surgery using radioactive technetium
(Tc99), requiring preoperative injection and lymphoscintigraphy. However, the
use of Tc99 poses significant burdens on patients, as it requires additional
hospital visits or travel to different hospital due to the limited availability
of nuclear medicine facilities. Tc99 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 Tc99 to patients, health care providers,
and society. Yet, the use of ICG for the SLN procedure 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.

The INFINITE trail aims to successfully implement ICG-fluorescence for
identifying the SLN by: 1) guiding the implementation process using the
Effective Implementation of Change model developed by Grol and Wensing; 2)
identifying and understanding the factors influencing implementation outcomes
(i.e., barriers and facilitators), through the use of CFIR (Consolidated
Framework for Implementation Research) determinants framework; 3) evaluating
the outcomes of implementation efforts using a mixed methods approach and
following the outcomes framework proposed by Proctor et al. 4) creating
conditions for nationwide implementation. Secondary aims to guide
implementation and create conditions for nationwide implementation (the
proposed implementation program) include: 1) develop a uniform medical protocol
for the use of ICG for the SLN procedure; 2) develop an implementation guide
that aligns with current practice 3) develop educational materials for
surgeons, modules for the curriculum of surgical residents (CASH), patient
information materials and organizing interactive meetings (workshops) for
surgical health care providers and their teams; 4) further substantiating the
effectiveness, safety, cost-effectiveness and impact on necessary FTE*s of
personnel. 5) disseminate and engage, increasing support and create a sense of
urgency for ICG implementation by organizing informational sessions during
annual conferences of the scientific associations; 6) Facilitate the scaling up
of the implementation of the ICG for the SLN procedure to all hospitals in the
Netherlands by incorporating ICG into the SLN guidelines.

ICG will be implemented in seven strategically chosen Dutch hospitals during
the INFINITE trial. These hospitals have been selected to represent different
areas, settings and sizes, ensuring broad applicability and support for
subsequent nationwide implementation.
The INFINITE trial is a multicenter hybrid effectiveness implementation study
that employs a stepped-wedge cluster randomized trial design across three
phases: Phase I) pre-implementation (Tc99); Phase II) transition period (Tc99
and ICG); Phase III) post-implementation (ICG).
Clusters will transition to the next phase at fixed intervals of three months
when the randomization order dictates, creating an iterative learning cycle.
This approach allows for regular evaluations of the implementation strategies,
process and products (protocol, implementation guide, educational materials and
patient information). Process evaluations will inform adjustments using the
ERIC-CFIR matching tool, ensuring swift integration of lessons learned to
enhance implementation in the next cluster.

Phase I (pre-implementation): SLN procedure with the standard of care using
Tc99, which implies Tc99 injection and lymphoscintigraphy the day or the
morning before surgery, followed by radio-guided surgery with a gamma-detection
probe.

Phase II (transition period): SLN procedure using ICG and controlled by Tc99.
Patients receive Tc99 injection and lymphoscintigraphy before surgery, with the
surgeon blinded for imaging results. During surgery, after administration of
general anesthesia and before axillary incision, 5mg (2 ml) ICG will be
injected periareolar. The SLN procedure is performed with fluorescent imaging
of ICG using a fluorescence camera. After excision of the SLN(*s), the standard
gamma detecting probe is used to test the excised nodes and the axilla for Tc99
activity as control. The axilla will also be explored by common sight and
palpation.

Phase III (post-implementation): SLN procedure using ICG as single tracer. 5 mg
(2 ml) ICG will be injected periareolar after administration of general
anesthesia and before axillary incision. The sentinel lymph node will be
visualized by fluorescent imaging using a fluorescence camera and excised.

Consenting patients will not experience any extra burden from ICG-fluorescence.
ICG will be administered under general anesthesia, so patients will not
experience extra discomfort, neither do they need extra site visits or
additional proceedings. ICG is safe to use: it is nonionizing and knows little
to no complications and adverse events. Considering a cut-off of 2 additional
nodes, the preferable topographic location of these nodes and the clinical
experience with additional lymph node sampling, we expect no increase in risk
of surgical morbidity. Patients might benefit from the intervention as ICG can
increase the identification rate and the lack of a pre-operative visit to the
Nuclear Medicine department for technetium injection. Filling out the
questionnaire regarding patient satisfaction of the SLN-procedure which will
take up about 10 to 15 minutes only. Thus, both risks and burden are
negligible.