Research Papers:

Intraoperative imaging identifies thymoma margins following neoadjuvant chemotherapy

Jane J. Keating _, Sarah Nims, Ollin Venegas, Jack Jiang, David Holt, John C. Kucharczuk, Charuhas Deshpande and Sunil Singhal

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Oncotarget. 2016; 7:3059-3067. https://doi.org/10.18632/oncotarget.6578

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Jane J. Keating1, Sarah Nims1, Ollin Venegas1, Jack Jiang1, David Holt2, John C. Kucharczuk1, Charuhas Deshpande3, Sunil Singhal1

1Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

2Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Perelman School of Medicine, Philadelphia, PA, USA

3Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

Correspondence to:

Sunil Singhal, e-mail: [email protected]

Keywords: molecular imaging, indocyanine green, near-infrared, margins

Received: August 20, 2015     Accepted: November 21, 2015     Published: December 12, 2015


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.

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