Diagnostic performance of receptor-specific surgical specimen staining correlate with receptor expression level

Broderick J. House, Jasmin M. Schaefer, Connor W. Barth, Scott C. Davis, Summer L. Gibbs

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Identification of tumor margins in the operating room in real time is a critical challenge for surgical procedures that serve as cancer cure. Breast conserving surgery (BCS) is particularly affected by this problem, with current reexcision rates above 25%. Due to a lack of clinically available methodologies for detection of involved or close tumor margins, much effort is focused on developing intraoperative margin assessment modalities that can aid in addressing this unmet clinical need. BCS provides a unique opportunity to design contrast-based technologies that are able to assess tumor margins independent from the patient, providing a rapid pathway from bench to bedside at a much lower cost. Since resected tissue is removed from the patient's blood supply, non-specific contrast agent uptake becomes a challenge due to the lack of clearance. Therefore, a dual probe, ratiometric fluorescence imaging approach was taken in an effort to reduce non-specific signal, and provide a modality that could demonstrate rapid, robust margin assessment on resected patient samples. Termed, dual-stain difference specimen imaging (DDSI), DDSI includes the use of spectrally unique, and fluorescently labeled target-specific, as well as non-specific biomarkers. In the present study, we have applied epidermal growth factor receptor (EGFR) targeted DDSI to tumor xenografts with variable EGFR expression levels using a previously optimized staining protocol, allowing for a quantitative assessment of the predictive power of the technique under biologically relevant conditions. Due to the presence of necrosis in the model tumors, ring analysis was employed to characterize diagnostic accuracy as measured by receiver operator characteristic (ROC) curve analysis. Our findings demonstrate the robust nature of the DDSI technique even in the presence of variable biomarker expression and spatial patterns. These results support the continued development of this technology as a robust diagnostic tool for tumor margin assessment in resected specimens during BCS.

Original languageEnglish (US)
Title of host publicationMolecular-Guided Surgery
Subtitle of host publicationMolecules, Devices, and Applications V
EditorsBrian W. Pogue, Sylvain Gioux
PublisherSPIE
ISBN (Electronic)9781510623668
DOIs
StatePublished - 2019
EventMolecular-Guided Surgery: Molecules, Devices, and Applications V 2019 - San Francisco, United States
Duration: Feb 2 2019Feb 4 2019

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume10862
ISSN (Print)1605-7422

Conference

ConferenceMolecular-Guided Surgery: Molecules, Devices, and Applications V 2019
CountryUnited States
CitySan Francisco
Period2/2/192/4/19

Keywords

  • Breast conserving surgery
  • Dual-stain difference specimen imaging
  • Image-guided surgery
  • Paired agent imaging
  • Tumor margin assessment

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Radiology Nuclear Medicine and imaging

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