No abstract

The use of high-frequency (HF) ultrasound (20-80 MHz) to determine tissue pathology is an inexpensive and real-time tool for differentiation of surgical margin specimens from breast conservation surgery (BCS). The development of this method as an intraoperative tool for BCS would greatly reduce the rate of re-excisions due to positive breast tissue margins. HF ultrasound was previously used in a 17-patient study to determine differences in breast tissue pathology of 34 surgical margins. Results from this pilot study demonstrated high accuracy, specificity, and sensitivity in the HF ultrasound data, and showed the immense potential of this method as a breast cancer detection tool. A large-scale validation study of this method was subsequently conducted using 349 margin specimens taken from 73 patients during BCS. Specimens ranged from 1-5 cm in length and width, 0.2-1.6 cm in thickness, and did not require any additional procedures or resection that affected the patient or surgical outcome. Each specimen was tested with HF ultrasound immediately following resection and then forwarded to pathology. Through-transmission data were collected from the specimens using two broadband, single-element transducers with a 50-MHz peak frequency (Olympus NDT, V358-SU), a HF square-wave pulser/receiver (UTEX, UT340), and a 1-GHz digital oscilloscope (Agilent, DSOX3104A). Peak density (the number of peaks and valleys in the 20-80 MHz frequency spectra range) and attenuation data were calculated from the ultrasonic spectra and waveforms, respectively. Peak density and attenuation correlate directly to tissue malignancy, and thresholds for these two parameters for differentiating benign vs. malignant tissue were determined using Fisher's Exact Test applied to the previously collected pilot study data. The peak density and attenuation results were then combined using a multivariate analysis. Since the ultrasonic measurements were collected on a per position basis (1-5 positions per margin), but the histopathology results were reported on a per specimen basis, the statistical measures for the ultrasonic results were calculated using two methods. First, the statistical measures were calculated based on a per position basis, where the pathology of each position was determined by the pathology results for the entire specimen. Second, the statistical measures were calculated based on a per specimen basis, where only one measurement position on each margin was selected (based on the highest peak density value) to correlate to the specimen pathology. The results of the first approach (per position basis) showed a sensitivity of 82.6%, a specificity of 72.3%, and an accuracy of 72.7%. The results of the second approach (per specimen basis) showed a sensitivity of 82.6%, a specificity of 61.7%, and an accuracy of 63.0%. The results of this study show potential for a rapid and inexpensive method of determining pathology of breast tissue surgical margins during BCS. This work was supported by funds from the Elsa U. Pardee Foundation, the Eppley Foundation for Research, the Western Alliance for Expanding Student Opportunities, theGovernor's Office of Economic Development of the State of Utah, the University of Utah, and Utah Valley University. Citation Format: Carter C, Neumayer LA, Factor RE, Doyle TE. Using high-frequency ultrasound (20-80 MHz) to differentiate malignant vs benign breast tissue in surgical margins [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-03-10.

Purpose: The sentinel lymph node (SLN) is biopsied during breast conservation surgery (BCS) since it is the first site of metastasis for breast cancer. If malignant, axillary lymph node dissection (ALND) may be performed to remove additional nodes in and around the affected breast, limiting the spread of the malignancy. Often, ALND results in hardship for the patient in the form of further surgeries, having nodes removed that may not be malignant, and in debilitating side effects. Developing a method to analyze SLNs intraoperatively would eliminate additional surgeries and the patient's associated suffering. This research aims to develop the use of high-frequency (HF) ultrasound (20-80 MHz) as a real-time analysis method to determine SLN status during BCS. Background: HF ultrasonic data from BCS tissue specimens were gathered from 73 patients at the Huntsman Cancer Institute, Salt Lake City, UT, immediately following surgery. In addition to 349 margin specimens, data were collected from 78 SLNs, with initial results displaying high statistical measures. A limitation of the SLN analyses, however, was that pathology results were provided only on a per sample basis, whereas the ultrasonic method often tested multiple positions on a node (max = 4, avg = 1.26). Because of the mismatch between the ultrasonic measurements (per position basis) and pathology results (per specimen basis), an ambiguity existed in how to best analyze the data. The aim of this study was to examine the scope of this ambiguity by determining the differences in statistical measures obtained by analyzing the SLN data on a per position basis versus a per specimen basis given the current data available. Method: HF ultrasound parameters extracted from the data were peak density (the number of peaks in the ultrasonic spectra) and attenuation. Both parameters correlate to tissue malignancy, and were used in a multivariate analysis to provide the final results. The statistical measures for the ultrasonic test results were calculated as follows: (1) per position basis: the pathology of each position was determined by the pathology results for the entire specimen; (2) per specimen basis: only one measurement position on each node was selected, based on the highest peak density value, to correlate to the specimen pathology. Results: The analyses revealed that the HF ultrasonic data yielded an accuracy, sensitivity, and specificity of 79.6%, 76.9%, and 80.0%, respectively, for the per position basis, and 84.6%, 87.5%, and 84.3%, respectively, for the per specimen basis. The results indicate that HF ultrasound provides intraoperative detection capabilities competitive with many SLN evaluation methods currently in use, including imprint cytology, frozen-section analysis, and qRT-PCR. Detailed analyses of the SLN pathology slides from the 73-patient study are currently being conducted to improve the correlations between the ultrasound results and histopathology. Image analysis methods are being used to quantify the extent of the malignant tissue in each SLN. This will provide pathology results on a per position basis, and thus more accurate, one-to-one correlations. These correlations would significantly further the development of HF ultrasound for real-time SLN evaluation. Citation Format: Khelfa S, Factor RE, Sanjinez DA, Zambrana AF, Doyle TE. Evaluation of sentinel lymph nodes with high-frequency ultrasound: Correlations to histopathology [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-05.