INFLUENCE: Indocyanine green Node FLUorEsceNCE study
Research type
Research Study
Full title
A prospective randomised study comparing indocyanine green (ICG) fluorescence combined with a standard tracer versus ICG alone for sentinel lymph node (SLN) detection in early breast cancer
IRAS ID
301478
Contact name
Vassilis Pitsinis
Contact email
Sponsor organisation
Tayside Health Board
Duration of Study in the UK
1 years, 5 months, 30 days
Research summary
Summary of Research
The most common form of breast cancers can spread to lymph nodes in the armpit, sentinel lymph nodes (SLN). Women usually have two SLNs although this varies from individual to individual. At the time of surgery to remove abreast tumour, the surgeon will also remove the SLNs. To help the surgeons visualise the SLNs, they usually inject two tracers, a fluorescent dye (Indocyanine Green fluorescence, ICG) and a either a blue dye (Patent Blue dye) into the breast or radioisotope, given systemically at an appointment prior to the surgery (standard care). The tracers are used to visualise the SLNs.
More than half of newly diagnosed breast cancer patients will undergo routine SLN biopsy annually in the UK (>25,000 cases). Blue dye is becoming less popular as a tracer due to potential allergic reactions and staining of cutaneous/breast tissues. In about one third of women this staining of the skin can last for 12 months and in about 1 in 12 women still have staining after 3 years. Drawbacks of radioisotope include availability, cost, patient inconvenience/discomfort, radiation exposure/disposal and mandatory licensing. Fluorescence navigation using ICG has high optical sensitivity and permits a real-time sequential SLN dissection guided by visualisation of lymphatic tissue and sentinel nodes.
It is hypothesized that fluorescence mapping can provide at least equivalent SLN detection rates but offer the opportunity for avoiding blue dye and eventually lead to improved cost-effectiveness if radioisotope is eventually abandoned for routine SLN biopsy. Abolition of blue dye with its associated risk of anaphylactic reaction (1-3%), skin tattooing and non-licensed use will be notable benefits of ICG.
Participants will be randomised to receive:
Tayside - either ICG plus Patent Blue Dye (standard care) or ICG alone (intervention)
Cambridge - either ICG plus radioisotope (standard care) or ICG alone (intervention).Summary of Results
A total of 100 patients were randomized between March and December 2022 with 3 patients excluded from analysis (non-receipt of treatment allocation). Amongst evaluable patients (n=97), the overall SNB identification rate was 96.9% and by tracer category as follows: ICG alone = 97.9% (46/47); ICG + RI = 100% (25/25); ICG + blue dye = 92% (23/25). For cohort 1, the procedural node positivity rates were 17% for ICG alone and 18% for ICG + RI with corresponding figures of 12% for ICG alone and 20% for ICG + blue dye for cohort 2. Mean procedural node retrieval per case was 2.5 in ICG alone Vs ICG + Blue Dye and 2.3 in ICG alone Vs ICG/RI cohorts. There were no significant differences (p>0.05) in performance of ICG alone or combined with a standard tracer, with ICG alone being non-inferior in terms of procedural and nodal detection rates. Similar conclusions were reached from a secondary analysis adjusting for BMI, age and mode of detection (screening/symptomatic). ICG fluorescence imaging permits real-time visualisation of lymphatics and gives an additional dimension to SNB that appears safe versus the competitive alternatives. These results confirm high sensitivity for fluorescence localisation alone for SNB with comparable performance to combined methods with blue dye or RI. The fluorochrome ICG is reliable as a sole tracer and avoids potential drawbacks of blue dye and RI including staining, allergic reactions, availability and costs.
REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
21/NW/0328
Date of REC Opinion
23 Nov 2021
REC opinion
Favourable Opinion