Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging

Abstract

Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0–2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon’s clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28–83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.

Toward the use of diffuse reflection spectroscopy for intra-operative tissue discrimination during sarcoma surgery

“…25 Finally, Gong et al implemented intraoperative margin assessment based on ICG in patients with STSs. 26 The ICG margins matched the permanent pathology margins in 56% of the patients. Larger sample sizes are needed to better quantify optimal dosage, timing, and the effect of histological subtypes.…”

“…Finally, Gong et al. implemented intraoperative margin assessment based on ICG in patients with STSs 26 . The ICG margins matched the permanent pathology margins in 56% of the patients.…”

“…Optical techniques have emerged as a potentially valuable tool for tissue sensing purposes in the medical field. For STS, a couple of optical techniques have been studied in recent years, including near-infrared autofluorescence, 22 Raman spectroscopy, 23 , 24 mid-infrared spectroscopy, 25 and indocyanine green fluorescence imaging (ICG) 26 . While some of these methods have demonstrated promising outcomes, not every approach is readily available, has a sufficient measurement volume, is offered as an automatic tumor detection model, or achieved an adequate level of accuracy for clinical application.…”

Emerging innovations and advancements in the treatment of extremity and truncal soft tissue sarcomas

“…19 Another study described the utilization of ICG in 18 patients with STS, which showed 89% specificity in tumor margins. 20 Nevertheless, some concerns with ICG include its cost implications due to early admission for administration and its nonspecific nature that may lead to over-resections. In contrast, 5-aminolevulinic acid (5-ALA) has shown promising utility in FGS for malignant gliomas, and is approved by the FDA.…”

“…In an extended case series, the utilization of ICG in patients with high‐grade sarcomas found a reduction in positive margin rate 19 . Another study described the utilization of ICG in 18 patients with STS, which showed 89% specificity in tumor margins 20 . Nevertheless, some concerns with ICG include its cost implications due to early admission for administration and its nonspecific nature that may lead to over‐resections.…”