Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: a single-centre feasibility study

Harlaar, Niels J.; Koller, Marjory; Jongh, Steven J de; Leeuwen, Barbara L. van; Hemmer, Patrick H. J.; Kruijff, Schelto; Ginkel, Robert J. van; Been, Lukas B.; Jong, Johannes S. de; Kats-Ugurlu, Gürsah; Linssen, Matthijs D.; Jorritsma-Smit, Annelies; Oosten, Marleen van; Nagengast, Wouter B.; Ntziachristos, Vasilis; Dam, Gooitzen M. van

doi:10.1016/s2468-1253(16)30082-6

Cited by 155 publications

(132 citation statements)

References 16 publications

(29 reference statements)

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“…Targeted NIR fluorescence imaging has already been studied in several clinical trials for colorectal, head and neck, pancreatic and renal cancer and has shown its potential and added value in intraoperative decision making 21,25,[31][32][33] . As a result of these trials, a variety of suitable biomarkers have been identified for NIR-fluorescence guided surgery.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Gooyer

Versleijen-Jonkers²,

Hillebrandt-Roeffen³

et al. 2020

Sci Rep

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Myxofibrosarcoma(MFS) is the most common soft tissue sarcoma(STS) in elderly patients. Surgical resection remains the main treatment modality but tumor borders can be difficult to delineate with conventional clinical methods. Incomplete resections are a common problem and local recurrence remains a clinical issue. A technique that has shown great potential in improving surgical treatment of solid tumors is tumor targeted imaging and image-guided surgery with near-infrared fluorescence. To facilitate this technique, it is essential to identify a biomarker that is highly and homogenously expressed on tumor cells, while being absent on healthy non-malignant tissue. The purpose of this study was to identify suitable molecular targets for tumor-targeted imaging of myxofibrosarcoma. Ten potential molecular targets for tumor targeted imaging were investigated with immunohistochemical analysis in myxofibrosarcoma tissue (n = 34). Results were quantified according to the immunoreactive score(IRS). Moderate expression rates were found for uPAR, PDGFRa and EMA/MUC1. High expression rates of VEGF and TEM1 were seen. Strong expression was most common for TEM1 (88.2%). These results confirms that TEM1 is a suitable target for tumor-targeted imaging of myxofibrosarcoma. Keywords Image-guided surgery; Immunohistochemistry; Molecular imaging; Myxofibrosarcoma; Soft tissue sarcoma; Tumor endothelial marker 1(TEM1), Vascular endothelial growth factor (VEGF).Myxofibrosarcoma (MFS) is a histological subtype of soft tissue sarcoma (STS) formerly classified as a myxoidtype malignant fibrous histiocytoma. It has been reclassified and defined as a distinct pathological entity in the World Health Organization (WHO) criteria set in 2002 1,2 . Myxofibrosarcoma is a relatively common sarcoma in the elderly that mainly arises in the extremities 3 . Primary MFS most often presents as a subcutaneous painless, slow growing nodule, but completely infiltrative growth patterns along fascial planes without formation of an evident tumor mass have also been described 4 . The low-grade lesions have a relatively low metastatic potential but show a significant propensity for local recurrences 5-8 . These recurrences show higher-grade histology in up to 50% of all cases compared to the primary tumor 3 . Subsequently, high and intermediate grade disease exhibits a greater metastatic potential, mainly metastasizing to the lungs and lymph nodes 7,9 . Current guidelines recommend wide surgical resection combined with pre or post-operative radiotherapy as the preferred treatment 10 . Despite this strategy, positive margins after surgery occur in up to 20% of cases and reported local relapse rates range from 15 to 65% [5][6][7][8]11 .Currently clinicians rely on conventional imaging modalities such as CT and MRI to determine the location and extent of tumor burden prior to surgery. Translating these conventional imaging modalities to the surgical theatre remains challenging, forcing the surgeon to depend mainly on tactile and visual cues during the procedure. P...

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Gooyer

Versleijen-Jonkers²,

Hillebrandt-Roeffen³

et al. 2020

Sci Rep

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“…Fluorescence imaging (FI) is ideal for intraoperative applications due to fast acquisition times (milliseconds), flexibility in application, and portability [2]. Various tumor-targeted near-infrared (NIR) fluorescence agents have been successfully studied in clinical trials [3][4][5][6]. Moreover, there is great potential for a broad range of clinical applications besides oncology, such as infectious and inflammatory diseases [7].…”

Section: Introductionmentioning

confidence: 99%

Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

et al. 2018

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Purpose: Intraoperative fluorescence imaging (FI) is a promising technique that could potentially guide oncologic surgeons toward more radical resections and thus improve clinical outcome. Despite the increase in the number of clinical trials, fluorescent agents and imaging systems for intraoperative FI, a standardized approach for imaging system performance assessment and post-acquisition image analysis is currently unavailable. Procedures: We conducted a systematic, controlled comparison between two commercially available imaging systems using a novel calibration device for FI systems and various fluorescent agents. In addition, we analyzed fluorescence images from previous studies to evaluate signal-to-background ratio (SBR) and determinants of SBR. Results: Using the calibration device, imaging system performance could be quantified and compared, exposing relevant differences in sensitivity. Image analysis demonstrated a profound influence of background noise and the selection of the background on SBR. Conclusions: In this article, we suggest clear approaches for the quantification of imaging system performance assessment and post-acquisition image analysis, attempting to set new standards in the field of FI.

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“…Comparable targeted fluorescent techniques have been established in other tumour types, e.g. in ovarian carcinoma [17, 53] and peritoneal metastases of colorectal carcinomas [18] targeting αvβ3-integrin or folate receptor α and VEGF-α, respectively. For the development of a similar approach in meningioma surgery, various biomarkers have been suggested, including epithelial membrane antigen (EMA), platelet-derived growth factor beta (PDGF-β), vascular endothelial growth factor A (VEGF-α), and somatostatin receptor type 2 (SSTR-2) [3, 5, 9, 11, 12, 16, 19, 21, 28, 30, 32, 38, 39, 43–45, 48, 52, 56].…”

Section: Introductionmentioning

confidence: 99%

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery

et al. 2018

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BackgroundMeningiomas are the most frequently occurring primary intracranial tumours in adults. Surgical removal can only be curative by complete resection; however surgical access can be challenging due to anatomical localization and local invasion of bone and soft tissues. Several intraoperative techniques have been tried to improve surgical resection, including intraoperative fluorescence guided imaging; however, no meningioma-specific (fluorescent) targeting has been developed yet. Here, we aimed to identify the most promising biomarkers for targeted intra-operative fluorescence guided meningioma surgery.MethodsOne hundred forty-eight meningioma specimens representing all meningioma grades were analysed using immunohistochemistry (IHC) on tissue microarrays (TMAs) to determine expression patterns of meningioma biomarkers epithelial membrane antigen (EMA), platelet-derived growth factor β (PDGF-β), vascular endothelial growth factor α (VEGF-α), and somatostatin receptor type 2 (SSTR-2). Subsequently, the most promising biomarker was selected based on TArget Selection Criteria (TASC). Marker expression was examined by IHC in 3D cell culture models generated from freshly resected tumour material.ResultsTMA-IHC showed strongest staining for SSTR-2. All cases were positive, with 51.4% strong/diffuse, 30.4% moderate/diffuse and only 18.2% focal/weak staining patterns. All tested biomarkers showed at least weak positivity in all meningiomas, regardless of WHO grade. TASC analysis showed that SSTR-2 was the most promising target for fluorescence guided imaging, with a total score of 21 (out of 22). SSTR-2 expression was determined on original patient tumours and 3D cultures of three established cultures.ConclusionsSSTR-2 expression was highly sensitive and specific in all 148 meningiomas, regardless of WHO grade. According to TASC analysis, SSTR-2 is the most promising receptor for meningioma targeting. After establishing in vitro meningioma models, SSTR-2 cell membrane expression was confirmed in two of three meningioma cultures as well. This indicates that specific fluorescence in an experimental setting can be performed for the further development of targeted fluorescence guided meningioma surgery and near-infrared fluorescent tracers targeting SSTR-2.

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Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: a single-centre feasibility study

Abstract: FP-7 Framework Programme BetaCure and SurgVision BV.

Cited by 155 publications

References 16 publications

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery

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