Intraoperative Near-Infrared Imaging of Surgical Wounds after Tumor Resections Can Detect Residual Disease

• Authors: Brian Madajewski, University of Pennsylvania; Brendan F. Judy, University of Pennsylvania; Anas Mouchli, University of Pennsylvania; Veena Kapoor, University of Pennsylvania; David Holt, University of Pennsylvania; Dongmei Wang, Emory University; Shuming Nie, Emory University; Sunil Singhal, University of Pennsylvania
• Journal Title: Clinical Cancer Research
• Volume: Volume 18, Number 20
• Publisher: American Association for Cancer Research | 2012-10-15, Pages 5741-5751
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1078-0432.CCR-12-1188
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Oncology; Engineering, Biomedical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; ENHANCED PERMEABILITY; INDOCYANINE GREEN; BREAST BIOPSIES; SURGERY; CANCER; LUMPECTOMY; RETENTION; ONCOLOGY; MARGINS; MODEL; Intraoperative imaging; Surgical oncology; Infrared; Margins; Indocyanine green

Abstract

Purpose: Surgical resection remains the most effective therapy for solid tumors worldwide. The most important prognostic indicator for cure following cancer surgery is a complete resection with no residual disease. However, intraoperative detection of retained cancer cells after surgery is challenging, and residual disease continues to be the most common cause of local failure. We hypothesized that visual enhancement of tumors using near-infrared imaging could potentially identify tumor deposits in the wound after resection. Experimental Design: A small animal model of surgery and retained disease was developed. Residual tumor deposits in the wound were targeted using an U.S. Food and Drug Administration-approved imaging agent, indocyanine green, by the enhanced permeability and retention effect. A novel handheld spectrometer was used to optically visualize retained disease after surgery. Results: We found residual disease using near-infrared imaging during surgery that was not visible to the naked eye or micro-CT. Furthermore, examination of tumor nodules was remarkably precise in delineating margins from normal surrounding tissues. This approach was most successful for tumors with increased neovasculature. Conclusions: The results suggest that near-infrared examination of the surgical wound after curative resection can potentially enable the surgeon to locate residual disease. The data in this study is the basis of an ongoing Phase I/II clinical trial in patients who undergo resection for lung and breast cancer.