Indocyanine green intraoperative guidance in spontaneous canine subcutaneous soft tissue sarcomas excision: an explorative study

Introduction: Near-Infrared Fluorescence (NIRF) with indocyanine green (ICG) for real-time guidance during the excision of human soft tissue sarcomas (STSs) has been investigated in few studies (1-4). However, due to STS rarity (~1% of all cancers), suitable models are needed to evaluate disease progression and treatment effectiveness. Spontaneous canine STS closely mimics the heterogeneity, treatment and complexity of human tumors and the use of NIRF-ICG is a new step forward in surgical management. This study aims to explore the feasibility of NIRF-ICG guidance during canine spontaneous STS excision. Methods: Owned dogs with subcutaneous STS, eligible for curative intent surgery were enrolled. Owners signed a written consent, and all procedures were in accordance with the best standard of veterinary practice. Previous neo-adjuvant treatments and radical surgeries (e.g. amputation) were exclusion criteria. In each dog, ICG (0.5mg/kg) was intravenously injected 24h before surgery. A hand-held imaging camera SPY -PHI QP system (Stryker) was used to assess fluorescence intensity of the tumor and background tissues. Tumor-to-background-ratio (TBR) was calculated and TBR>2 was considered fluorescent. Any fluorescence-driven changes of planned surgery and/or the presence of fluorescent tissue in the tumor bed (TB) after excision were recorded and the histologic status of margins were assessed. Results and discussion: Ten dogs with STS were enrolled. All tumors had an up-take of NIRF-ICG (Figure 1) with a TBR>2 (mean 18,41 ± 4,76). NIRF-ICG confirmed the planned surgery in 5/10 STSs. In the remaining 5 STSs, the surgical margins were extended in according with fluorescence signal and 3 of them had histological infiltrated margins (HIM). No residual ICG fluorescence was observed in 8/10 TB after tumor removal. Overall, 7/10 STSs had non-HIM: in 6/7 STSs, TB was non-fluorescent (real negative), while 1/7 was fluorescent (false positive). Of the remaining 3/10 STSs with HIM, 2/3 had a non-fluorescent TB (false negative) and 1/3 was fluorescent (real positive). Although ICG is a non- targeted probe, this explorative study suggests that its use could help minimize the microscopic residual disease in canine STS. Such promising results are in line with those obtained in humans and will be confirmed in further studies. Conclusion: This study shows the feasibility of NIRF-ICG in guiding canine STS removal. While the use of specific probes may offer a promising future approach, their applicability in veterinary and human clinical practice may be limited due to the heterogeneity of potential targets across histotypes. Further clinical studies using NIRF-ICG in canine STS may help defining the next milestones in both animal and human clinical research. + Novelty: This study on NIRF-ICG guidance in canine subcutaneous STS excision, encourage the exploration of new goals in translational clinical research. + Impact: Spontaneous canine STS could represent a translational model to investigate NIRF-ICG guidance and other future approaches in human STS surgery.