Detection of breast carcinoma with an ICG enhanced optical imaging device in breast cancer patients.

Breast cancer is the most common form of cancer and second leading cause of
death in women in Europe and the USA, with 450,000 new cases and 120.000 deaths
yearly. Over the last thirty years, wide-spread mammographic screening,
technological developments and raised physicians- and self-awareness have led
to a rapid increase in the diagnosis of small, non-palpable breast cancer.
Surgery of primary breast cancer is dependent on the resection of the primary
tumor and identification of cancer spread to lymph nodes (LNs), both
independent prognostic factors for survival and recurrence of disease. Since
breast sparing lumpectomy combined with radiotherapy is generally sufficient as
a treatment for T1-T2 breast tumours in appropriately selected patients, breast
conserving therapy (BCT) has become the standard treatment. BCT is considered
to be less stressful compared to radical mastectomy and offers better cosmetic
results and reduced wound infection risk. The most important disadvantage of
BCT is the life-long risk for local recurrence of the primary tumour, in which
case additional surgery is necessary. In 20-40% of the patients, after primary
excisions there are positive resection margins. With new imaging technologies,
this number may be reduced. In case of breast conserving treatment the aim of
the procedures is to obtain optimal locoregional control with optimal cosmetic
results. New innovative imaging modalities like NIRF imaging intend to improve
the detection of resection margins to be positive for tumor. This may decrease
the number of re-excisions and/or irradiation, and ultimately leading to
decreased costs, decreased co-morbidity and decreased psychological distress on
the patient.

Ergonomics and function of the imaging system - the NIRF imaging system should
not interfere with the standard lumpectomy procedure and used safely by the
surgeon while detection of ICG within the tumour takes place. Duration: 1,5
hour clinical procedure.

Interventional study: a phase 0 technical feasibility study / non-randomized,
open label, uncontrolled, single group assignment.
The study will be carried out in collaboration with the Technical University of
Munich, Institute of Biological and Medical Imaging. The actual study will be
carried out at the University Medical Center Groningen, Department of Surgery.

The study protocol is designed as follows:
1. Selection of patients with operable histology proven invasive breast cancer
(T1-2cN0-1) are asked for participation and informed consent at the outpatient
clinic for the proposed study if the apply to the inclusion criteria. Copies of
the proposed study protocol are available at the outpatient clinic. Patients
have at least 24 hours to decide whether they want to participate or not.
2. After approval and documented informed consent, a pregnancy test is
performed and in case of a positive test the patient cannot be included. Next,
the operative procedure is planned together with the NIRF imaging protocol. The
pharmacist of the UMCG is informed of inclusion of the patient together with
the planned date of operation for delivery of ICG.
3. at the day of admission (one day prior to surgery), the standard surgical
procedure for lumpectomy, combined with ICG intravenous injection in the
operating room (OR) is again explained to the patient.
4. the day prior to surgery, the ICG compound will be delivered by the Hospital
Pharmacy at the OR for i.v. injection.
5. during anesthesia ICG will be injected with a dose of 0.3 mg/kg (i.e. 1 ml
of volume in a dose of 5 mg/ml).

The burden associated with participation consists of an additional injection of
indocyanin green (ICG) i.v. during anaesthesia for the detection of the primary
tumour. Additionally, there is a chance of longer operative procedure by using
a NIRF imaging camera (~30 minutes).
1. The possible most serious adverse event for injection of ICG is an allergic
and anaphylactic reaction.
2. The possible effect of prolonged anesthesia because of testing the camera
system and detection of the primary tumour is limited in itself because of a
total time of no longer than 2 hours.
3. There is no risk or burden of using the intraoperative imaging device, all
necessary test for use of electrical devices in the OR are covered.
4. There is no risk of infection; the imaging device will be covered by special
designed sterile drapes to prevent the risk of infection during a surgical
procedure.