open access
Objective
In
ovarian cancer, two of the most important prognostic factors for
survival are
completeness of staging and completeness of cytoreductive
surgery. Therefore, intra-operative visualization of tumor lesions is of
great importance. Preclinical data already demonstrated tumor
visualization in a
mouse-model using near-infrared (NIR) fluorescence
imaging and indocyanine green (ICG) as a result of enhanced permeability
and retention (EPR). The aim of this study was to determine feasibility
of intraoperative ovarian cancer metastases imaging using NIR
fluorescence imaging and ICG in a clinical setting.
Methods
Ten
patients suspected of ovarian cancer scheduled for staging or
cytoreductive surgery were included. Patients received 20 mg ICG
intravenously after opening the abdominal cavity. The mini-FLARE NIR
fluorescence imaging system was used to detect NIR fluorescent lesions.
Results
6
out of 10 patients had malignant disease of the ovary or fallopian
tube, of which 2 had metastatic disease outside the pelvis. Eight
metastatic lesions were detected in these 2 patients, which were all NIR
fluorescent. However, 13 non-malignant lesions were also NIR
fluorescent, resulting in a
false-positive rate of 62%. There was no
significant difference in tumor-to-background ratio between malignant
and benign lesions (2.0 vs 2.0; P=0.99).
Conclusions
This
is the first clinical trial demonstrating intraoperative detection of
ovarian cancer metastases using NIR fluorescence imaging and ICG.
Despite detection of all malignant lesions, a high false-positive rate
was observed. Therefore, NIR fluorescence imaging using ICG based on the
EPR effect is
not satisfactory for the detection of ovarian cancer
metastases. The need for tumor-specific intraoperative agents remains.
Trial Registration
ISRCTN Registry
ISRCTN16945066
.....Clinical feasibility trials using this effect with ICG in breast cancer
patients in a pre-operative diagnostic setting and in gastric cancer
patients during endoscopic surgery showed that it was possible to
distinguish tumor from surrounding tissue [
18–
23]. In addition, Kosaka et al.[
24]
detected small ovarian (1–2 mm in size) cancer implants using NIR
fluorescent imaging after intravenous (IV) administration of ICG in a
mouse model. Pathophysiological heterogeneity of solid tumors, for
examples in size, presence of necrosis, or presence of vascular
mediators may influence accumulation of macromolecules in tumor tissue [
25,
26].
It is therefore not clear if all preclinical results can be translated to the clinic.