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Assessment of breast cancer surgical margins with multimodal optical microscopy: A feasibility clinical study.

ABSTRACT: Providing surgical margin information during breast cancer surgery is crucial for the success of the procedure. The margin is defined as the distance from the tumor to the cut surface of the resection specimen. The consensus among surgeons and radiation oncologists is that there should be no tumor left within 1 to maximum 2 mm from the surface of the surgical specimen. If a positive margin remains, there is substantial risk for tumor recurrence, which may also result in potentially reduced cosmesis and eventual need for mastectomy. In this paper we report a novel multimodal optical imaging instrument based on combined high-resolution confocal microscopy-optical coherence tomography imaging for assessing the presence of potential positive margins on surgical specimens. Since rapid specimen analysis is critical during surgery, this instrument also includes a fluorescence imaging channel to enable rapid identification of the areas of the specimen that have potential positive margins. This is possible by specimen incubation with a cancer specific agent prior to imaging. In this study we used a quenched contrast agent, which is activated by cancer specific enzymes, such as urokinase plasminogen activators (uPA). Using this agent or a similar one, one may limit the use of high-resolution optical imaging to only fluorescence-highlighted areas for visualizing tissue morphology at the sub-cellular scale and confirming or ruling out cancer presence. Preliminary evaluation of this technology was performed on 20 surgical specimens and testing of the optical imaging findings was performed against histopathology. The combination of the three imaging modes allowed for high correlation between optical image analysis and histological ground-truth. The initial results are encouraging, showing instrument capability to assess margins on clinical specimens with a positive predictive value of 1.0 and a negative predictive value of 0.83.

SUBMITTER: Scimone MT

PROVIDER: S-EPMC7877783 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Assessment of breast cancer surgical margins with multimodal optical microscopy: A feasibility clinical study.

Scimone Mark T MT Krishnamurthy Savitri S Maguluri Gopi G Preda Dorin D Park Jesung J Grimble John J Song Min M Ban Kechen K Iftimia Nicusor N

PloS one 20210211 2

Providing surgical margin information during breast cancer surgery is crucial for the success of the procedure. The margin is defined as the distance from the tumor to the cut surface of the resection specimen. The consensus among surgeons and radiation oncologists is that there should be no tumor left within 1 to maximum 2 mm from the surface of the surgical specimen. If a positive margin remains, there is substantial risk for tumor recurrence, which may also result in potentially reduced cosme ...[more]

PMID: 33571221

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Project description:BackgroundSurgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery.Methods and findingsOur methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study. Careful evaluation of the long-term benefits to patients of the use of DESI-MSI for surgical margin evaluation is also needed to determine its value in clinical practice.ConclusionsOur findings provide evidence that the molecular information obtained by DESI-MSI/Lasso from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens. With further development, we believe the described methodology could be routinely used for intraoperative surgical margin assessment of pancreatic cancer.

Dataset Information

Assessment of breast cancer surgical margins with multimodal optical microscopy: A feasibility clinical study.

Publications

Assessment of breast cancer surgical margins with multimodal optical microscopy: A feasibility clinical study.

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