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

Zeger Rijs,Fijs W B Van Leeuwen,Alexander L Vahrmeijer,Hans Gelderblom,Alida F W Van Der Steeg,Michiel A J Van De Sande,Naweed Shifai,Cornelis F M Sier,Bernadette Jeremiasse

doi:10.3390/biomedicines9101388

Zeger Rijs, Fijs W B Van Leeuwen + Show 7 more

Open Access

https://doi.org/10.3390/biomedicines9101388

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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.

Highlights

We conclude with recommendations for the experiments needed before fluorescence-guided surgery (FGS) can be implemented for pediatric OS, Ewing sarcoma (ES), and RMS patients
Due to the presence of vascular endothelial growth factor A (VEGF-A) in pediatric OS and RMS (Tables 2 and 3), testing BevacizumabIRDye800CW is a relatively straightforward option which could pave the road towards the clinical implementation of FGS in pediatric OS and RMS patients
Targets were considered promising for FGS if the expression was evaluated in at least 20 tissue samples for a tumor subtype and more than 50% of the samples stained positive

Summary

Introduction

Apart from increasing local recurrence-free and overall survival rates, complete resections help reduce total dosages of adjuvant chemo- and or radiotherapy [11,17] This is relevant for pediatric patients as survivors face risks of common cancer treatmentrelated side effects, such as impaired growth and development, organ dysfunction, and secondary malignancies [21,22]. Esposito et al reported their results in 76 laparoscopic and/or robotic procedures (40 left varicocelectomies, 13 renal procedures, 12 cholecystectomies, 5 tumor excisions, 3 lymphoma excisions, 3 thoracoscopic procedures, 2 lobectomies, and 1 lymph node biopsy) They concluded that ICG-guidance is useful because it is easy to apply, safe, and allows for the better identification of anatomical structures as well as easier surgical dissection or resection in challenging cases. The technology is used in trial settings for pediatric surgical oncology [39]

Indocyanine Green for Sarcoma Resections

Disadvantages of Using Antibodies for Fluorescence-Guided Surgery and

Findings

Conclusions