Purpose

Complete resection is a key prognostic factor for survival in patients with soft tissue sarcoma (STS), in humas and companion animals alike. Fluorescence-guided surgery could improve resection accuracy. As dogs are frequently affected by STS, they serve as a model to test an anti-α_vβ₃ integrin targeting near-infrared fluorescent (NIRF) dye (Angiostamp^TM800) for fluorescence-guided surgery in STS to evaluate its safety and feasibility in dogs, and if it translates into a clinically relevant benefit compared to the standard of care with regards to completeness of surgery and local recurrence. Furthermore, we aimed to correlate target expression and NIRF-signal intensity.

Methods

Twenty dogs with STS were randomly allocated to either receive Angiostamp™ (NIRF group) or physiologic saline (control group) preoperatively. The researchers were blinded for treatment, and resections were adapted based on the NIRF-signal, if needed. Margin status was histologically determined at the 1 and 3 cm margin. The tumor-to-background ratio was measured in native tissue biopsies and formalin-fixed tissue. The fluorescent area was compared to the corresponding tumor areas as confirmed by histology using the Dice coefficient. Target expression was quantified by immunohistochemistry and correlated to NIRF-signal ratios.

Results

A fluorescent signal was detected in all 10 tumors of the NIRF group, with a tumor-to-background ratio of 7.4 ± 5.8 in native biopsies and 13.5 ± 10.9 in formalin-fixed tissue. In the NIRF group, resection margins were adapted in 5/10 cases, leading to complete resection and preventing R1 in four of these cases. In the NIRF and control group 9/10 and 8/10 resections were R0, with one local recurrence in each group and one sarcoma-related death in the NIRF group. The NIRF-signal correlated with the histologically confirmed tumor area (Dice coefficient 0.75 ± 0.17). Target expression was higher in tumor compared to peritumoral tissue (p < 0.0003) and showed a moderate correlation with the NIRF-signal (r = 0.6516, p < 0.0001).

Conclusion

Fluorescence-guided surgery using Angiostamp™ can pinpoint residual disease in the tumor bed and contributes to an improved resection accuracy in canine STS.

中文翻译：

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靶向抗 αvβ3 整合素近红外荧光染料用于荧光引导切除狗自然发生的软组织肉瘤的评价

 目的

完全切除是软组织肉瘤 （STS） 患者、HUMA 和伴侣动物生存的关键预后因素。荧光引导手术可以提高切除准确性。由于狗经常受到 STS 的影响，它们作为模型来测试靶向近红外荧光 （NIRF） 染料 （Angiostamp^TM800） 的抗 α_{vβ 3} 整合素用于 STS 中的荧光引导手术，以评估其在狗中的安全性和可行性，以及它是否转化为临床相关益处与护理标准相比手术完整性和局部复发。此外，我们旨在将靶标表达与 NIRF 信号强度相关联。

 方法

20 只患有 STS 的狗被随机分配在术前接受 Angiostamp™ （NIRF 组） 或生理盐水 （对照组）。研究人员对治疗采用盲法，如果需要，根据 NIRF 信号调整切除。在 1 cm 和 3 cm 边缘组织学确定边缘状态。在天然组织活检和福尔马林固定组织中测量肿瘤与背景比。使用 Dice 系数将荧光区域与组织学证实的相应肿瘤区域进行比较。通过免疫组织化学定量靶标表达并与 NIRF 信号比率相关。

 结果

在 NIRF 组的所有 10 种肿瘤中均检测到荧光信号，天然活检中的肿瘤背景比为 7.4 ± 5.8，福尔马林固定组织中为 13.5 ± 10.9。在 NIRF 组中，5/10 病例调整了切除切缘，其中 4 例导致完全切除并阻止 R1。在 NIRF 和对照组中，9/10 和 8/10 切除为 R0，每组有 1 例局部复发，NIRF 组有 1 例肉瘤相关死亡。NIRF 信号与组织学证实的肿瘤区域相关 （Dice 系数 0.75 ± 0.17）。与瘤周组织相比，肿瘤中的靶标表达较高 （p < 0.0003），并且与 NIRF 信号呈中等相关性 （r = 0.6516，p < 0.0001）。

 结论

使用 Angiostamp™ 的荧光引导手术可以精确定位肿瘤床中的残留病灶，并有助于提高犬 STS 的切除准确性。