Dataset Information

Back-Table Fluorescence-Guided Imaging for Circumferential Resection Margin Evaluation Using Bevacizumab-800CW in Patients with Locally Advanced Rectal Cancer.

ABSTRACT: Negative circumferential resection margins (CRM) are the cornerstone for the curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients, tumor-positive resection margins are detected on histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool for evaluating the CRM directly after surgical resection to improve tumor-negative CRM rates. Methods: LARC patients treated with neoadjuvant chemoradiotherapy received an intravenous bolus injection of 4.5 mg of bevacizumab-800CW, a fluorescent tracer targeting vascular endothelial growth factor A, 2-3 d before surgery (ClinicalTrials.gov identifier: NCT01972373). First, for evaluation of the CRM status, back-table fluorescence-guided imaging (FGI) of the fresh surgical resection specimens (n = 8) was performed. These results were correlated with histopathology results. Second, for determination of the sensitivity and specificity of bevacizumab-800CW for tumor detection, a mean fluorescence intensity cutoff value was determined from the formalin-fixed tissue slices (n = 42; 17 patients). Local bevacizumab-800CW accumulation was evaluated by fluorescence microscopy. Results: Back-table FGI correctly identified a tumor-positive CRM by high fluorescence intensities in 1 of 2 patients (50%) with a tumor-positive CRM. For the other patient, low fluorescence intensities were shown, although (sub)millimeter tumor deposits were present less than 1 mm from the CRM. FGI correctly identified 5 of 6 tumor-negative CRM (83%). The 1 patient with false-positive findings had a marginal negative CRM of only 1.4 mm. Receiver operating characteristic curve analysis of the fluorescence intensities of formalin-fixed tissue slices yielded an optimal mean fluorescence intensity cutoff value for tumor detection of 5,775 (sensitivity of 96.19% and specificity of 80.39%). Bevacizumab-800CW enabled a clear differentiation between tumor and normal tissue up to a microscopic level, with a tumor-to-background ratio of 4.7 ± 2.5 (mean ± SD). Conclusion: In this proof-of-concept study, we showed the potential of back-table FGI for evaluating the CRM status in LARC patients. Optimization of this technique with adaptation of standard operating procedures could change perioperative decision making with regard to extending resections or applying intraoperative radiation therapy in the case of positive CRM.

SUBMITTER: de Jongh SJ

PROVIDER: S-EPMC7198377 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Back-Table Fluorescence-Guided Imaging for Circumferential Resection Margin Evaluation Using Bevacizumab-800CW in Patients with Locally Advanced Rectal Cancer.

de Jongh Steven J SJ Tjalma Jolien J J JJJ Koller Marjory M Linssen Matthijs D MD Vonk Jasper J Dobosz Michael M Jorritsma-Smit Annelies A Kleibeuker Jan H JH Hospers Geke A P GAP Havenga Klaas K Hemmer Patrick H J PHJ Karrenbeld Arend A van Dam Gooitzen M GM van Etten Boudewijn B Nagengast Wouter B WB

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20191018 5

Negative circumferential resection margins (CRM) are the cornerstone for the curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients, tumor-positive resection margins are detected on histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool for evaluating the CRM directly after surgical resection to improve tumor-negative CRM rates. <b>Methods:</b> LARC patients treated with neoadjuvant chemorad ...[more]

PMID: 31628218

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Project description:The standard treatment for glioblastoma multiforme (GBM) remains maximal safe surgical resection. Here, we evaluated the ability of a systemically administered antibody-dye probe conjugate (cetuximab-IRDye 800CW) to provide sufficient fluorescent contrast for surgical resection of disease in both subcutaneous and orthotopic animal models of GBM. Multiple luciferase-positive GBM cell lines (D-54MG, U-87MG, and U-251MG; n = 5) were implanted in mouse flank and tumors were fluorescently imaged daily using a closed-field near-infrared (NIR) system after cetuximab-IRDye 800CW systemic administration. Orthotopic models were also generated (n = 5), and tumor resection was performed under white light and fluorescence guidance using an FDA-approved wide-field NIR imaging system. Residual tumor was monitored using luciferase imaging. Immunohistochemistry was performed to characterize tumor fluorescence, epidermal growth factor receptor (EGFR) expression, and vessel density. Daily imaging of tumors revealed an average tumor-to-background (TBR) of 4.5 for U-87MG, 4.1 for D-54MG, and 3.7 for U-251MG. Fluorescence intensity within the tumors peaked on day-1 after cetuximab-IRDye 800CW administration, however the TBR increased over time in two of the three cell lines. For the orthotopic model, TBR on surgery day ranged from 19 to 23 during wide-field, intraoperative imaging. Surgical resection under white light on day 3 after cetuximab-IRDye 800CW resulted in an average 41% reduction in luciferase signal while fluorescence-guided resection using wide-field NIR imaging resulted in a significantly (P = 0.001) greater reduction in luciferase signal (87%). Reduction of luciferase signal was found to correlate (R (2) = 0.99) with reduction in fluorescence intensity. Fluorescence intensity was found to correlate (P < 0.05) with EGFR expression in D-54MG and U-251MG tumor types but not U-87MG. However, tumor fluorescence was found to correlate with vessel density for the U-87MG tumors. Here we show systemic administration of cetuximab-IRDye 800CW in combination with wide-field NIR imaging provided robust and specific fluorescence contrast for successful localization of disease in subcutaneous and orthotopic animal models of GBM.

Project description:Background:A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods:Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results:A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3-4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT-assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c-index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4-5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion:The presence of advanced cT status, poor tumour differentiation, and CT-assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.

Dataset Information

Back-Table Fluorescence-Guided Imaging for Circumferential Resection Margin Evaluation Using Bevacizumab-800CW in Patients with Locally Advanced Rectal Cancer.

Publications

Back-Table Fluorescence-Guided Imaging for Circumferential Resection Margin Evaluation Using Bevacizumab-800CW in Patients with Locally Advanced Rectal Cancer.

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