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.
Highlights
Mediastinal masses comprise a diverse group of benign and malignant tumor types such as thymomas, thymic carcinomas, germ cell tumors and neurogenic tumors [1]
Near infrared (NIR) molecular imaging is useful to identify tumor margins during surgery; the value of this technology has not been evaluated for tumors that have been pre-treated with chemotherapy
NIR intraoperative molecular imaging is a rapidly emerging tool for detecting tumor cells, metastases and lymph nodes with cancer cells [9,10,11,12]
Summary
Mediastinal masses comprise a diverse group of benign and malignant tumor types such as thymomas, thymic carcinomas, germ cell tumors and neurogenic tumors [1]. The most important prognostic indicator for mediastinal thymomas and thymic carcinomas is a complete surgical resection [2,3,4]. Pre-treatment of mediastinal tumors can result in local inflammatory responses and scarring that blurs tumor margins As a consequence this increases the complexity of the operation, risks an incomplete resection and can result in a local recurrence. Molecular imaging is an emerging technology to improve surgical resections by identifying small tumors, delineating tumor margins, and localizing lymph nodes that may contain metastatic cancer cells during surgery. This technique is based on fluorescent molecular agents and imaging devices that improve tumor visualization. Intraoperative molecular imaging with a nearinfrared (NIR) fluorescent contrast agent, indocyanine green (ICG), has been used for colorectal cancer, lung cancer and sentinel lymph node mapping [9,10,11,12,13,14]
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