Tumor Resection Guided by Intraoperative Indocyanine Green Dye Fluorescence Angiography Results in Negative Surgical Margins and Decreased Local Recurrence in an Orthotopic Mouse Model of Osteosarcoma

Abstract

Background Surgical resection with negative margins is the foundation of extremity sarcoma management. Failure to achieve negative surgical margins can result in local recurrence (LR), a potentially devastating complication. Indocyanine green (ICG) is a US FDA-approved fluorophore previously used to guide carcinoma resections. We investigated the potential of ICG as an intraoperative guide during experimental sarcoma resection. Methods Fifty 6-week-old immunocompetent Balb/c female mice received left proximal tibia paraphyseal injections of 5 × 10 5 K7M2 murine osteosarcoma cells. Animals were separated into two groups ( n = 25 each): (1) ICG-assisted surgical resection; and (2) no ICG-assisted resection. Resections were performed 4 weeks after primary tumor engraftment. All animals received 7.5 ug ICG via retro-orbital injection 12 h prior to surgery. ICG fluorescence measurements and clinical evaluations were performed 4 weeks after resection to detect LR. Results Eleven of 25 animals from each group developed gross tumors. Four weeks after resection, group 1 had 0/11 tumor recurrences, while group 2 had recurrences in 9/11 (81.8%) experimental mice ( p < 0.0002) (Fig. 2 ). There was a 100% NPV in group 1, and no tumor recurrence with fluorescence-free margins after the primary surgery. Group 2 had a 100% positive predictive value for the development of an LR if any fluorescent signal was present at the surgical margin after resection. Conclusion Intraoperative ICG guidance led to reliably negative surgical margins and a diminished LR rate. Given the benign safety profile of ICG and its prior clinical success, these results could be immediately translatable to the clinical realm.

Transplantation of autologous extracellular vesicles for cancer-specific targeting

“…Indeed, ICG-loaded EVs could work as in vivo tumor-selective markers, guiding more precise treatment of cancer lesions. Augmented-reality devices that take advantage of such effects could improve surgical precision, achieving tumor-free margins and ultimately obtaining improved local control of cancer 31 . The current practice of intra/peri-tumor direct injection of ICG to stain local lymph nodal drainage in some tumors 27 could be largely surpassed by the demonstrated specificity of ICG-loaded EVs.…”

Indocyanine Green for Leakage Control in Isolated Limb Perfusion

“…In oncologic surgery, it is used for sentinel lymph node mapping and intraoperative identification of tumors [44]. Due to intratumoral injection, exact tumor margins can be visualized, ensuring safe resection without damage of surrounding tissue [45,46]. Moreover, it can be injected into the epineurium of nerves to improve the intraoperative visualization and to avoid accidental damage [47].…”

Children's Oncology Group's 2023 blueprint for research: Surgery

“…Currently, COG surgeons are studying ICG-guided SLNB for WT tumor in collaboration with SIOP surgeons. [51][52][53][54][55][56]59,60 To overcome passive targeting by ICG, molecularly targeted fluorescent agents have been developed that specifically bind the tissue of interest and are conjugated to a fluorescent molecule. Ideally, nonspecific binding is minimal, and the tumor-to-background ratio (TBR) is maximized.…”