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

Ann Surg Oncol. 2019 Mar;26(3):894-898. doi: 10.1245/s10434-018-07114-9. Epub 2018 Dec 27.

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 × 105 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.

MeSH terms

  • Animals
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / pathology
  • Bone Neoplasms / surgery*
  • Female
  • Fluorescein Angiography / methods*
  • Fluorescence*
  • Fluorescent Dyes
  • Indocyanine Green / metabolism
  • Intraoperative Care
  • Margins of Excision
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control*
  • Optical Imaging / methods*
  • Osteosarcoma / diagnostic imaging
  • Osteosarcoma / pathology
  • Osteosarcoma / surgery*
  • Surgery, Computer-Assisted / methods*

Substances

  • Fluorescent Dyes
  • Indocyanine Green