A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins

Int J Cancer. 2015 Nov 15;137(10):2403-12. doi: 10.1002/ijc.29611. Epub 2015 Jun 3.

Abstract

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82 and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78 and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence.

Keywords: image analysis; intraoperative imaging; logistic models; optical fluorescence imaging; soft tissue sarcoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Neoplasms / pathology
  • Bone Neoplasms / surgery*
  • Diagnostic Imaging / methods*
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Intraoperative Care
  • Mice
  • Neoplasm, Residual / diagnosis*
  • Prospective Studies
  • Sarcoma / pathology
  • Sarcoma / surgery*
  • Sensitivity and Specificity