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Back-table fluorescence-guided imaging for circumferential resection margin evaluation in locally advanced rectal cancer patients using bevacizumab-800CW.

Authors
  • de Jongh, Steven J1
  • Tjalma, Jolien J J1
  • Koller, Marjory1
  • Linssen, Matthijs D1
  • Vonk, Jasper1
  • Dobosz, Michael2
  • Jorritsma-Smit, Annelies1
  • Kleibeuker, Jan H1
  • Hospers, Geke A P1
  • Havenga, Klaas1
  • Hemmer, Patrick H J1
  • Karrenbeld, Arend1
  • van Dam, Gooitzen M1
  • van Etten, Boudewijn1
  • Nagengast, Wouter B3
  • 1 University Medical Center Groningen, University of Groningen, Netherlands. , (Netherlands)
  • 2 Discovery Oncology, Pharmaceutical Research and Early Development, Roche Innovation Center Munich, Germany. , (Germany)
  • 3 University of Groningen, University Medical Center Groningen, Netherlands. , (Netherlands)
Type
Published Article
Publication Date
Oct 18, 2019
Identifiers
DOI: 10.2967/jnumed.119.232355
PMID: 31628218
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Negative circumferential resection margins (CRM) are the cornerstone for curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients tumor-positive resection margins are detected upon histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool to evaluate the CRM directly after surgical resection in order to improve tumor-negative CRM rates. Methods: LARC patients that were treated with neoadjuvant chemoradiotherapy received an intravenous bolus injection of 4.5 mg bevacizumab-800CW, a fluorescent tracer targeting vascular endothelial growth factor A (VEGFA), 2-3 days before surgery (NCT01972373). To evaluate the CRM status, back-table fluorescence-guided imaging (FGI) was performed of the fresh surgical resection specimens (N = 8). These results were correlated to histopathology. Secondly, to determine the sensitivity and specificity of bevacizumab-800CW for tumor detection, a mean fluorescence intensity (MFI) cut-off value was determined on 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 one of two patients (50%) with a tumor-positive CRM. The other patient showed low fluorescence intensities, although (sub-)millimeter tumor deposits were present <1 mm of the CRM. FGI correctly identified 5/6 tumor-negative CRMs (83%). The one patient with false-positive findings had a marginal negative CRM of only 1.4 mm. ROC analysis of fluorescence intensities of formalin-fixed tissue slices gave an optimal MFI cut-off value for tumor detection of 5,775 (sensitivity and specificity of 96.16% and 80.39% respectively). 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 to evaluate 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 case of positive CRMs. Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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