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WIREs Syst Biol Med
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Image‐guided surgery in cancer: A strategy to reduce incidence of positive surgical margins

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Primary treatment for many solid cancers includes surgical excision or radiation therapy, with or without the use of adjuvant therapy. This can include the addition of radiation and chemotherapy after primary surgical therapy, or the addition of chemotherapy and salvage surgery to primary radiation therapy. Both primary therapies, surgery and radiation, require precise anatomic localization of tumor. If tumor is not targeted adequately with initial treatment, disease recurrence may ensue, and if targeting is too broad, unnecessary morbidity may occur to nearby structures or remaining normal tissue. Fluorescence imaging using intraoperative contrast agents is a rapidly growing field for improving visualization in cancer surgery to facilitate resection in order to obtain negative margins. There are multiple strategies for tumor visualization based on antibodies against surface markers or ligands for receptors preferentially expressed in cancer. In this article, we review the incidence and clinical implications of positive surgical margins for some of the most common solid tumors. Within this context, we present the ongoing clinical and preclinical studies focused on the use of intraoperative contrast agents to improve surgical margins. This article is categorized under: Laboratory Methods and Technologies > Imaging
Schematic of surgical margins showing tumor present at the edge of the resection (positive margins) or absence of tumor at the edge of the resection (negative margins)
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Images reprinted with permission from published reports of fluorescence‐guided surgery in patients with head and neck cancer (a), ovarian cancer (b), or breast cancer (C). (a) Trial imaging workflow. Real‐time imaging was performed with a wide‐field near‐infrared (NIR) imaging system in the clinic on (1) day 0, 1, and in the (2) operating room on day 3 post‐cetuximab‐IRDye800 infusion. (3) During postresection processing, resected tissues were imaged with a closed‐field NIR imaging system. (4) Following histologic preparation, a corresponding slide was imaged in surgical pathology using a fluorescence scanning system (Rosenthal et al., 2015). (b) Quantification of tumor deposits ex vivo. (A, B) Color image (A) with the corresponding tumor‐specific fluorescence image (B) of a representative area in the abdominal cavity. (C) Scoring was based on three different color images (median 7, range 4–22) and their corresponding fluorescence images (FLI) (median 34, range 8–81); P < .001 by five independent surgeons (van Dam et al., 2011). (c) Primary tumor image. Red, green, blue (RGB) color images with putative malignant tissue region‐of‐interest (ROI) were produced by adding the ROI area as a solid green color blended into the color image. (A) Two specimens including primary tumor at the surface of the specimens before and after the application of the overlay. (B) Positive lymph node before and after application of the overlay (Unkart et al., 2017)
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