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

Biomedicines, vol. 9, pp. 1388

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.

Authors 9

1. Zeger Rijs corresponding Aachen Department of Orthopedic Surgery

   Leiden University Medical Center

   Affiliation as printed

   Department of Orthopedic Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

2. Bernadette Jeremiasse

   Princess Máxima Center

   Affiliation as printed

   Department of Surgery, Princess Maxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands

3. Naweed Shifai Aachen Department of Orthopedic Surgery

   Leiden University Medical Center

   Affiliation as printed

   Department of Orthopedic Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

4. Hans A. J. Gelderblom Aachen Department of Medical Oncology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

5. Cornelis F.M. Sier Aachen Department of Surgery, Leiden University Medical Center

   Leiden University Medical Center · Percuros (Netherlands)

   Affiliation as printed

   Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

   Percuros BV, 2333 CL Leiden, The Netherlands

6. Alexander L. Vahrmeijer Aachen Department of Surgery, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

7. Fijs W. B. van Leeuwen Aachen Interventional Molecular Imaging Laboratory Department of Radiology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

8. Alida F. W. van der Steeg

   Princess Máxima Center

   Affiliation as printed

   Department of Surgery, Princess Maxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands

9. Michiel A. J. van de Sande Aachen Department of Orthopedic Surgery

   Leiden University Medical Center

   Affiliation as printed

   Department of Orthopedic Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands