Candidate Biomarkers for Specific Intraoperative Near-Infrared Imaging of Soft Tissue Sarcomas: A Systematic Review

Rijs, Zeger; Shifai, A Naweed; Bosma, Sarah; Kuppen, Peter J. K.; Vahrmeijer, Alexander L.; Keereweer, Stijn; Bovée, Judith V.M.G.; Sande, Michiel A. J. van de; Sier, Cornelis F.M.; Driel, Pieter B A A van

doi:10.3390/cancers13030557

Cited by 10 publications

(12 citation statements)

References 172 publications

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“…These immunophenotypic characteristics of GISTs provide possible opportunities to develop fluorescent tracers that bind GIST cell-specific biomarkers and improve the feasibility of intraoperative NIRF imaging. Future research should aim to explore the potential of tracers that bind KIT, DOG1, and other biomarkers, described in the literature as helpful for NIRF imaging in malignancies with similar immunophenotypic characteristics to GIST [30].…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study

Kalisvaart

Meijer

Bijlstra

et al. 2022

Cancers

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Background: Optimal intraoperative tumor identification of gastrointestinal stromal tumors (GISTs) is important for the quality of surgical resections. This study aims to assess the potential of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to improve intraoperative tumor identification. Methods: Ten GIST patients, planned to undergo resection, were included. During surgery, 10 mg of ICG was intravenously administered, and NIRF imaging was performed at 5, 10, and 15 min after the injection. The tumor fluorescence intensity was visually assessed, and tumor-to-background ratios (TBRs) were calculated for exophytic lesions. Results: Eleven GIST lesions were imaged. The fluorescence intensity of the tumor was visually synchronous and similar to the background in five lesions. In one lesion, the tumor fluorescence was more intense than in the surrounding tissue. Almost no fluorescence was observed in both the tumor and healthy peritoneal tissue in two patients with GIST lesions adjacent to the liver. In three GISTs without exophytic growth, no fluorescence of the tumor was observed. The median TBRs at 5, 10, and 15 min were 1.0(0.4–1.2), 1.0(0.5–1.9), and 0.9(0.7–1.2), respectively. Conclusion: GISTs typically show similar fluorescence intensity to the surrounding tissue in NIRF imaging after intraoperative ICG administration. Therefore, intraoperatively administered ICG is currently not applicable for adequate tumor identification, and further research should focus on the development of tumor-specific fluorescent tracers for GISTs.

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Section: Discussionmentioning

confidence: 99%

Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study

Kalisvaart

Meijer

Bijlstra

et al. 2022

Cancers

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“…A total of eight biomarkers were selected for IHC evaluation based on their potential to detect FGS in MFS. Biomarkers were chosen based on a clinical trial that had already included MFS patients using vascular endothelial growth factor A (VEGF-A) as a target for FGS and a systematic review that selected targets for FGS in soft tissue sarcomas [ 19 , 21 ]. Selected biomarkers were: tumor endothelial marker-1 (TEM-1), vascular endothelial growth factor receptor-1 (VEGFR-1), vascular endothelial growth factor receptor-2 (VEGFR-2), VEGF-A, epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet-derived growth factor receptor-α (PDGFR-α), and cluster of differentiation antigen 40 (CD40, also known as TNFRS5 or p50).…”

Section: Methodsmentioning

confidence: 99%

“…Ideally, this biomarker is still present on residual cells after preoperative therapy. Based on these criteria, promising clinically translatable tumor-specific biomarkers for MFS and other sarcomas have been identified in a recent systematic review [ 21 ]. Since several dedicated NIRF camera systems are already on the market, evaluating a suitable biomarker is currently one of the most important steps to orchestrating successful FGS in MFS [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method

et al. 2023

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Introduction: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons’ ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). Methods: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. Results: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. Conclusion: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.

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“…First, clinically available antibodies and their respective targeting antigens for these tumor types were identified from PubMed and clinicaltrials.gov (Supplementary Tables S1 and S2). This search was restricted to therapeutic antibodies which have been previously or are currently evaluated in clinical trials because these antibodies can be relatively time-and cost-efficiently modified into fluorescent tracers [24,55]. Second, PubMed searches were performed to find important information for target selection (Appendix A).…”

Section: Targeted Fluorescence-guided Surgery For Os Es and Rmsmentioning

confidence: 99%

“…The real-time intraoperative visualization of malignancies could improve resection accuracy by aiding the surgeon discriminate between healthy and malignant tissue. Fluorescence-guided surgery (FGS) is one of the promising technological advances facilitating the visualization of tumors in real-time during surgery [23,24].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Candidate Biomarkers for Specific Intraoperative Near-Infrared Imaging of Soft Tissue Sarcomas: A Systematic Review

Cited by 10 publications

References 172 publications

Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study

Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study

Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method

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

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