Intraoperative imaging of residual ovarian cancer after neoadjuvant chemotherapy using indocyanine green

Interval debulking surgery has similar outcomes and less morbidity compared with primary debulking in advanced ovarian cancer. However, there is controversy regarding the selection of chemotherapy-resistant clones. Complete resection is an essential prerequisite, and near-infrared surgery combined with various techniques for highlighting malignant foci strives to achieve actual complete resection. This study investigated the role of indocyanine green (ICG) in identifying additional residual malignant foci during interval debulking of apparently intact peritoneum not deemed clinically suspicious under white light inspection.

Patients diagnosed with stage III or IV high-grade serous ovarian carcinoma, older than 18 years of age, with satisfactory hepatic and renal functions who underwent neoadjuvant chemotherapy according to the institutional protocol and were scheduled to undergo interval debulking surgery between 2020 and 2022 were deemed suitable for inclusion after agreeing to the study protocol and acknowledging no contraindications for the administration of the ICG product. After laparotomy and white light inspection, using bolus administration of ICG, additional suspect peritoneal samples in near infrared (defined by clinical hyper- or hypointensity areas compared with surrounding ICG fluorescence using the Zeiss Opmi Pentero 800 surgical microscope, that were not deemed clinically suspicious under white light) were excised. Descriptive statistics were inferred and the chi-square test was used for the comparison of excised areas. The Kaplan-Meier method was deployed for computing the overall survival and progression-free survival of the cohort. All statistical analyses were performed using IBM SPSS Statistics software.

Fifteen patients with a median age of 56 years were included. Most cases (n=10, 66.7%) were International Federation of Gynecology and Obstetrics (FIGO) stage III, and all patients received four to seven cycles of neoadjuvant platinum chemotherapy, with 40% of regimens using bevacizumab. The mean interval between neoadjuvant treatment and surgery was 39 (median 42, range 20-78) days. A total of 39 suspect additional peritoneal samples were analyzed, with 41% confirming malignant foci. The positive predictive value (PPV) for malignant foci was 30% in ICG hyperintense areas and 46% in ICG hypointense areas. Germline BRCA1/2 mutant patients and using neoadjuvant bevacizumab led to a higher PPV for ICG hypointense areas (60% and 72.7%, respectively). Overall, the number of additionally resected pathologically confirmed malignant lesions through ICG fluorescence increased by 25%.

The use of ICG was associated with an increase in the resection of samples with residual malignant foci. Overall, hypointense areas had a higher positive PPV for malignant foci in comparison with hyperintense ICG areas (46% vs 30%), which could be interpreted in the context of dynamic changes in the tumor microenvironment or enhanced permeability and retention effect following neoadjuvant chemotherapy.