title: Intraoperative imaging identifies thymoma margins following neoadjuvant chemotherapy.
abstract: Near infrared (NIR) molecular imaging is useful to identify tumor margins during surgery; however, the value of this technology has not been evaluated for tumors that have been pre-treated with chemotherapy. We hypothesized that NIR molecular imaging could locate mediastinal tumor margins in a murine model after neoadjuvant chemotherapy. Flank thymomas were established on mice. Two separate experiments were performed for tumor margin detection. The first experiment compared (i) surgery and (ii) surgery + NIR imaging. The second experiment compared (iii) preoperative chemotherapy + surgery, and (iv) preoperative chemotherapy + surgery + NIR imaging. NIR imaging occurred following systemic injection of indocyanine green. Margins were assessed for residual tumor cells by pathology. NIR imaging was superior at detecting retained tumor cells during surgery compared to standard techniques (surgery alone vs. surgery + NIR imaging, 20% vs. 80%, respectively). Following chemotherapy, the sensitivity of NIR imaging of tumor margins was not significantly altered. The mean in vivo tumor-to-background fluorescence ratio was similar in the treatment-naïve and chemotherapy groups ((p = 0.899): 3.79 ± 0.69 (IQR 3.29 - 4.25) vs. 3.79 ± 0.52 (IQR 3.40 - 4.03)). We conclude that chemotherapy does not affect tumor fluorescence or identification of retained cancer cells at margins.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Keating
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nims
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Ollin
authors.initials: O
authors.lastname: Venegas
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Holt
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Kucharczuk
authors.affiliation: Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Charuhas
authors.initials: C
authors.lastname: Deshpande
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D008479:Mediastinal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual / Q000175:diagnosis*; D061848:Optical Imaging / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013945:Thymoma / Q000175:diagnosis* / Q000188:drug therapy / Q000601:surgery
keywords: indocyanine green; margins; molecular imaging; near-infrared