Intraoperative Near-Infrared Fluorescence Guided Surgery Using Indocyanine Green (ICG) May Aid the Surgical Removal of Benign Bone and Soft Tissue Tumours

Benign bone and soft tissue tumours encompass a broad, heterogenous range of tumours with varying clinical characteristics. Treatment choices vary depending on factors such as histology, location and symptoms; despite the advancement in minimally invasive treatments such as cryoablation or radiofrequency ablation [1] and medical therapies such as denosumab for giant cell tumour (GCT) of bone [2], treatment often involves surgery of some form. In the case of bone tumours, this often consists of curettage, whereas in their soft tissue counterpart, this is usually marginal excision. Despite being benign, these tumours can be locally aggressive and recur if adequate local control is not achieved. GCTs of the bone for example have reported local recurrence rates of up to 65% [3], with around 4% metastasising to the lungs [4], which can ultimately prove fatal. For bone tumours, studies have demonstrated that wide resection is associated with decreased rates of local recurrence (LR) compared to intralesional curettage [4], although the complications associated with extensive bone resection means that intralesional curettage remains the standard of care. Curettage of maximal tumour tissue is clearly important, however judging the completeness of curettage with visual assessment alone is difficult. Similarly, the soft tissue variant, tenosynovial giant cell tumour (TS-GCT) has significant local recurrence rates following surgery, with a recent multicentre study reporting LR rates of 28.6% at 5 years; diffuse subtype and knee location were independent risk factors for increased LR [5]. A recent systematic review of TS-GCT treatment agreed, suggesting that the high LR rate necessitates the development of improved treatments [6].

Indocyanine green (ICG) is a tricarbocyanine dye which fluoresces in the near-infrared (NIR) spectrum [7]. Historically, it was used for the assessment of cardiac output [8] and hepatic function [9], although more recently it has been used for fluorescence guided surgery (FGS). The use of ICG for FGS was originally described for the identification of satellite lymph nodes 10, 11, 12, 13, 14, 15, but has since been used to identify solid malignant tumours intraoperatively in multiple carcinoma sub-types 16, 17, 18, 19, 20, 21. Our group published the first case series demonstrating the utility of ICG for FGS in sarcoma [22] prior to publishing an updated case series demonstrating a reduction in the positive margin rate [23]. Despite this, the use of FGS with ICG in benign soft tissue and bone lesions is not yet widely described. The use of ICG for FGS in GCT of bone and atypical cartilaginous tumours has recently been described as part of a mixed population of benign and malignant bone tumours, in which patients were given ICG the day before the procedure [24]; 12/13 GCTs included fluoresced whilst the atypical cartilaginous tumour did not. The results demonstrated that the technology was particularly effective at the detection of residual tumour in piecemeal excisions. Despite the growing popularity of FGS using ICG in solid cancers, including sarcoma 25, 26, and some benign bone tumours, there are a few sporadic reports in the literature describing the use of FGS with ICG to guide excision of benign soft tissue tumours [27], with no reports to our knowledge in the extremities.

Theoretically, allowing the surgeon to visualise the tumour intraoperatively may provide similar benefits in benign tumour surgery as it does for their malignant counterparts, allowing them to identify remaining tumour and increase the completeness of resection or curettage. Given that previous studies have demonstrated reduced rates of local recurrence with wide resection as opposed to intralesional surgery [4], it stands to reason that increasing the completeness of curettage/excision has the potential to reduce the LR rate. The main aim of this study was to ascertain whether benign bone and soft tissue tumours fluoresce when the patient is administered with ICG intravenously preoperatively. We also aimed to investigate whether FGS using ICG may help the surgeon to identify residual tumour tissue when removing benign bone and soft tissue lesions, whilst ensuring that the technology is safe for patients and acceptable for surgeons.

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