Introducing Fluorescence-Guided Surgery for Pediatric Ewing, Osteo-, and Rhabdomyosarcomas: A Literature Review

Abstract

Sarcomas are a rare heterogeneous group of malignant neoplasms of mesenchymal origin which represent approximately 13% of all cancers in pediatric patients. The most prevalent pediatric bone sarcomas are osteosarcoma (OS) and Ewing sarcoma (ES). Rhabdomyosarcoma (RMS) is the most frequently occurring pediatric soft tissue sarcoma. The median age of OS and ES is approximately 17 years, so this disease is also commonly seen in adults while non-pleiomorphic RMS is rare in the adult population. The mainstay of all treatment regimens is multimodal treatment containing chemotherapy, surgical resection, and sometimes (neo)adjuvant radiotherapy. A clear resection margin improves both local control and overall survival and should be the goal during surgery with a curative intent. Real-time intraoperative fluorescence-guided imaging could facilitate complete resections by visualizing tumor tissue during surgery. This review evaluates whether non-targeted and targeted fluorescence-guided surgery (FGS) could be beneficial for pediatric OS, ES, and RMS patients. Necessities for clinical implementation, current literature, and the positive as well as negative aspects of non-targeted FGS using the NIR dye Indocyanine Green (ICG) were evaluated. In addition, we provide an overview of targets that could potentially be used for FGS in OS, ES, and RMS. Then, due to the time- and cost-efficient translational perspective, we elaborate on the use of antibody-based tracers as well as their disadvantages and alternatives. Finally, we conclude with recommendations for the experiments needed before FGS can be implemented for pediatric OS, ES, and RMS patients.

CORR Insights®: What Are the Complication Rates and Factors Associated With Total Femur Replacement After Tumor Resection? Findings From the Japanese Musculoskeletal Oncology Group

“…c A literature review discussed the positive and negative aspects of both targeted and nontargeted NIR, suggested targets for common pediatric sarcomas, and outlined the experiments that need to be done before widespread implementation of fluorescenceguided surgery [10].…”

“…A review summarizing the state of the art in sarcoma margin assessment reported that NIR fluorescence intraoperative imaging may provide surgical benefits in understanding tumor anatomy, perfusion, lymphatic drainage, margins and metastases [1]. A literature review discussed the positive and negative aspects of both targeted and nontargeted NIR, suggested targets for common pediatric sarcomas, and outlined the experiments that need to be done before widespread implementation of fluorescence-guided surgery [10]. A status report about the ongoing randomized controlled trial comparing negative-pressure wound therapy versus conventional wound dressing and associated postoperative wound complications after surgical removal of deep-seated, high-malignant soft tissue sarcoma of the extremities or trunk wall indicated that the results may have implications for all major musculoskeletal resections, including total femur resection [20].…”

Progresses in Fluorescence Imaging Guidance for Bone and Soft Tissue Sarcoma Surgery

“…Many factors can influence the EPR effect, including tumor type, size, and vascular mediators. As a result, the intensity of the ICG signal is unpredictable ( 20 ). If the patient has a fracture or ischemia at the surgical site during surgery, it will cause false-positive results and affect the judgment.…”

Application of Indocyanine Green Fluorescence Imaging in Assisting Biopsy of Musculoskeletal Tumors

“…After intravenous administration, ICG binds to serum proteins and appears as macromolecules in the circulation. ICG can passively accumulate in tumor tissue through enhanced permeability and retention (EPR) [ 9 ] and has been used to visualize tumors or sentinel lymph nodes in breast [ 10 ], gastric [ 11 ], lung [ 12 ], liver [ 13 ], and several other types of surgery [ 14 , 15 ]. Recently, some studies have reported the surgical resection of bone and soft tissue sarcomas with ICG-guided near-infrared imaging, which may prove that this technology can be safely used in the treatment of bone and soft tissue tumors [ 16 , 17 ].…”