Margin Assessment In Breast Conserving Surgery Research Articles

A Comparison of Spectroscopy and Imaging Techniques Utilizing Spectrally Resolved Diffusely Reflected Light for Intraoperative Margin Assessment in Breast-Conserving Surgery: A Systematic Review and Meta-Analysis.

Up to 19% of patients require re-excision surgery due to positive margins in breast-conserving surgery (BCS). Intraoperative margin assessment tools (IMAs) that incorporate tissue optical measurements could help reduce re-excision rates. This review focuses on methods that use and assess spectrally resolved diffusely reflected light for breast cancer detection in the intraoperative setting. Following PROSPERO registration (CRD42022356216), an electronic search was performed. The modalities searched for were diffuse reflectance spectroscopy (DRS), multispectral imaging (MSI), hyperspectral imaging (HSI), and spatial frequency domain imaging (SFDI). The inclusion criteria encompassed studies of human in vivo or ex vivo breast tissues, which presented data on accuracy. The exclusion criteria were contrast use, frozen samples, and other imaging adjuncts. 19 studies were selected following PRISMA guidelines. Studies were divided into point-based (spectroscopy) or whole field-of-view (imaging) techniques. A fixed-or random-effects model analysis generated pooled sensitivity/specificity for the different modalities, following heterogeneity calculations using the Q statistic. Overall, imaging-based techniques had better pooled sensitivity/specificity (0.90 (CI 0.76-1.03)/0.92 (CI 0.78-1.06)) compared with probe-based techniques (0.84 (CI 0.78-0.89)/0.85 (CI 0.79-0.91)). The use of spectrally resolved diffusely reflected light is a rapid, non-contact technique that confers accuracy in discriminating between normal and malignant breast tissue, and it constitutes a potential IMA tool.

Stereoscopic optical palpation for tumour margin assessment in breast-conserving surgery

Optical palpation is an emerging set of techniques that utilise an optical imaging system to generate images of mechanical contrast in tissue with micro- to milli-scale resolution. Recently, digital cameras have been proposed as the imaging system, due to their affordability and portability, realising cost-effective and rapid tissue assessment. Despite these benefits, existing camera-based optical palpation techniques use indirect strain estimation approaches and it is not possible to acquire both photographs and stress maps of the tissue, resulting in low strain sensitivity (∼100 mε) and inaccurate co-registration with tissue features. In this paper, we propose a new camera-based optical palpation system, termed stereoscopic optical palpation (SOP) that exploits stereoscopic imaging from two parallel cameras to directly map the strain of a compliant layer that is placed on top of the tissue. Stress maps are then generated from the measured strain and the pre-characterised mechanical properties of the layer, providing images with mechanical contrast derived from the elasticity of the underlying tissue. Using SOP, we demonstrate a strain sensitivity of 4.2 mε, a 24-fold improvement over previous camera-based optical palpation techniques. In addition, by embedding phosphorescent microparticles in the compliant layer, we demonstrate sequential acquisition of stress maps and visible-light photographs under different illumination conditions, providing accurate image co-registration between features in the stress map and the visual position on the tissue surface. We perform SOP on silicone phantoms and freshly excised human breast specimens. We compare SOP images with OCT-based optical palpation and histology for validation, demonstrating its capability for rapid and reliable imaging and the potential for tumour margin assessment in breast-conserving surgery.

Specimen mammography for intraoperative margin assessment in breast conserving surgery: a meta-analysis

In breast conserving surgery (BCS), specimen mammography is one of the most widely used intraoperative methods of assessing margin status. We performed a meta-analysis to evaluate the diagnostic accuracy of specimen mammography. Literature databases including PubMed, Cochrane Library, Web of Science, and EMBASE were searched prior to Jun 2022. A total of 1967 patients were included from 20 studies. A pooled analysis, heterogeneity testing, threshold effect testing, publication bias analysis, and subgroup analyses were performed from extracted data. The pooled weighted values were a sensitivity of 0.55 (95% confidence interval [CI], 0.47–0.63), a specificity of 0.85 (95% CI, 0.78–0.90), a diagnostic odds ratio of 7 (95% CI, 4–12), and a pooled positive likelihood ratio of 3.7 (95% CI 2.6–5.5). The area under the receiver operator characteristic curve was 0.75 (95% CI 0.71–0.78). In the subgroup analysis, the pooled specificity in the positive margin defined as tumor at margin subgroup was lower than the other positive margin definition subgroup (0.82 [95% CI: 0.71, 0.92] vs. 0.87 [95% CI: 0.80, 0.94], p = 0.01). Our findings indicated that specimen mammography was an accurate intraoperative imaging technique for margin assessment in BCS.

Radiopaque tissue transfer and X-ray system versus standard specimen radiography for intraoperative margin assessment in breast-conserving surgery: randomized clinical trial.

BackgroundReduction of positive margin rate (PMR) in breast-conserving surgery (BCS) of non-palpable breast cancer remains a challenge. The efficacy of intraoperative specimen radiography (SR) is unclear. This randomized trial evaluated whether the PMR was reduced by the use of devices that allow precise localization of the affected margins.MethodsPatients with microcalcification-associated breast cancer undergoing planned BCS were enrolled. Study participants were randomized to receive either SR with radiopaque tissue transfer and X-ray system (KliniTrayTM) or the institutional standard procedure (ISO). In all patients with a radiological margin less than 5 mm, an immediate re-excision was conducted. The primary outcome was the PMR. Risk factors for positive margins and the effect of immediate re-excision on final surgery were secondary analyses.ResultsAmong 122 randomized patients, 5 patients were excluded due to the extent of primary surgery and 117 were available for analysis. Final histopathology revealed a PMR of 31.7 per cent for the KliniTrayTM group and 26.3 per cent for the ISO group (P = 0.127). Independent factors for positive margins were histological tumour size more than 30 mm (adjusted OR (aOR) 10.73; 95 per cent c.i. 3.14 to 36.75; P < 0.001) and specimen size more than 50 mm (aOR 6.65; 95 per cent c.i. 2.00 to 22.08; P = 0.002). Immediate re-excision due to positive SR led to an absolute risk reduction in positive margins of 13.6 per cent (from 42.7 to 29.1 per cent).ConclusionSpecimen orientation with a radiopaque tissue transfer and X-ray system did not decrease the PMR in patients with microcalcification-associated breast cancer; however, SR and immediate re-excision proved to be helpful in the reduction of PMR.Registration numberDRKS00011527 (https://www.drks.de).

Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery With a Novel Pegulicianine Fluorescence–Guided System

Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time. To collect safety and initial efficacy data on the novel pegulicianine fluorescence-guided system (pFGS) when used to identify residual cancer in the tumor bed of female patients undergoing BCS. This prospective single-arm open-label study was conducted as a nonrandomized multicenter controlled trial at 16 academic or community breast centers across the US. Female patients 18 years and older with newly diagnosed primary invasive breast cancer or ductal carcinoma in situ DCIS undergoing BCS were included, excluding those with previous breast cancer surgery and a history of dye allergies. Of 283 consecutive eligible patients recruited, 234 received a pegulicianine injection and were included in the safety analysis; of these, 230 were included in the efficacy analysis. Patients were enrolled between February 6, 2018, and April 10, 2020, and monitored for a 30-day follow-up period. Data were analyzed from April 10, 2020, to August 5, 2021. Participants received an injection of a novel imaging agent (pegulicianine) a mean (SD) of 3.2 (0.9) hours prior to surgery at a dose of 1 mg/kg. After completing standard of care (SOC) excision, pFGS was used to scan the lumpectomy cavity to guide the removal of additional shave margins. Adverse events and sensitivity, specificity, and reexcision rate. Of 234 female patients enrolled (median [IQR] age, 62.0 [55.0-69.0] years), 230 completed the trial and 1 patient with a history of allergy to contrast agents had an anaphylactic reaction and recovered without sequelae. Correlation of pFGS with final margin status on a per-margin analysis showed a marked improvement in sensitivity over standard pathology assessment of the main lumpectomy specimen (69.4% vs 38.2%, respectively). On a per-patient level, the false-negative rate of pFGS was 23.7% (9 of 38), and sensitivity was 76.3% (29 of 38). Among 32 patients who underwent excision of pFGS-guided shaves, pFGS averted the need for reexcision in 6 (19%). In this pilot feasibility study, the safety profile of pegulicianine was consistent with other imaging agents used in BCS, and was associated with a reduced need for second surgery in patients who underwent intraoperative additional excision of pFGS-guided shaves. These findings support further development and clinical performance assessment of pFGS in a prospective randomized trial. ClinicalTrials.gov Identifier: NCT03321929.

Stereoscopic Optical Palpation for Tumour Margin Assessment in Breast-Conserving Surgery

Stereoscopic Optical Palpation for Tumour Margin Assessment in Breast-Conserving Surgery

Development of intraoperative assessment of margins in breast conserving surgery: a narrative review.

We intend to provide an informative and up-to-date summary on the topic of intraoperative assessment of margins in breast conserving surgery (BCS). Conventional methods as well as cutting-edge technologies are analyzed for their advantages and limitations in the hope that clinicians can turn to this for reference. This review can also offer guidance for technicians in the future design of intraoperative margin assessment tools. Achieving negative margins during BCS is one of the vital factors for preventing local recurrence. Conducting intraoperative margin assessment can ensure negative margins to a large extent and possibly relieve patients of the anguish of re-interventions. In recent years, innovative methods for margin assessment during BCS are advancing rapidly. And there is a lack of summary regarding the development of intraoperative margin assessment in BCS. A PubMed search with keywords "intraoperative margin assessment" and "breast conserving surgery" was conducted. Relevant publications were screened manually for its title, abstract and even full text to determine its true relevance. Publications on neo-adjuvant therapy and intraoperative radiotherapy were excluded. References from the searched articles and other supplementary articles were also looked into. Conventional methods for margin assessment yields stable outcome but its use is limited because of the demand on pathology staff and the trade-off between time and precision. Conventional imaging techniques pass the workload to radiologists at the cost of a significantly low duration of time. Involving artificial intelligence for image-based assessment is a further improvement. However, conventional imaging is inherently flawed in that occult lesions can't show on the image and the showing ones are ambiguous and open to interpretation. Unconventional techniques which base their judgment on cellular composition are more reassuring. Nonetheless, unconventional techniques should be subjected to clinical trials before putting into practice. And studies regarding comparison between conventional methods and unconventional methods are also needed to evaluate their relative efficacy.

Low-Field NMR Relaxometry for Intraoperative Tumour Margin Assessment in Breast-Conserving Surgery.

Simple SummaryBreast cancer is the most diagnosed cancer for women, and clear surgical margins in breast-conserving surgery (BCS) are essential for preventing recurrence. In this study, the potential of fast field-cycling 1H-NMR relaxometry as a new tool for intraoperative margin assessment was evaluated. The technique allows the determination of the tissue proton relaxation rates as a function of the applied magnetic field on small tissue samples excised from surgical specimens, at the margins of tumour resection, prior to histopathological analysis. It was found that a good accuracy in margin assessment, i.e., a sensitivity of 92% and a specificity of 85%, can be achieved. The discriminating ability shown by the relaxometric assay relies mainly on the difference of fat/water content between healthy and tumour cells. The information obtained has the potential to support the surgeon in real-time margin assessment during BCS.As conserving surgery is routinely applied for the treatment of early-stage breast cancer, the need for new technology to improve intraoperative margin assessment has become increasingly important. In this study, the potential of fast field-cycling 1H-NMR relaxometry as a new diagnostic tool was evaluated. The technique allows the determination of the tissue proton relaxation rates (R1), as a function of the applied magnetic field, which are affected by the changes in the composition of the mammary gland tissue occurring during the development of neoplasia. The study involved 104 small tissue samples obtained from surgical specimens destined for histopathology. It was found that a good accuracy in margin assessment, i.e., a sensitivity of 92% and a specificity of 85%, can be achieved by using two quantifiers, namely (i) the slope of the line joining the R1 values measured at 0.02 and 1 MHz and (ii) the sum of the R1 values measured at 0.39 and 1 MHz. The method is fast, and it does not rely on the expertise of a pathologist or cytologist. The obtained results suggest that a simplified, low-cost, automated instrument might compete well with the currently available tools in margin assessment.

Concept for using magnetic particle imaging for intraoperative margin analysis in breast-conserving surgery

Breast-conserving surgery (BCS) is a commonly utilized treatment for early stage breast cancers but has relatively high reexcision rates due to post-surgical identification of positive margins. A fast, specific, sensitive, easy-to-use tool for assessing margins intraoperatively could reduce the need for additional surgeries, and while many techniques have been explored, the clinical need is still unmet. We assess the potential of Magnetic Particle Imaging (MPI) for intraoperative margin assessment in BCS, using a passively or actively tumor-targeted iron oxide agent and two hardware devices: a hand-held Magnetic Particle detector for identifying residual tumor in the breast, and a small-bore MPI scanner for quickly imaging the tumor distribution in the excised specimen. Here, we present both hardware systems and demonstrate proof-of-concept detection and imaging of clinically relevant phantoms.

Intraoperative [18F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study

IntroductionIn women undergoing breast-conserving surgery (BCS), 20–25% require a re-operation as a result of incomplete tumour resection. An intra-operative technique to assess tumour margins accurately would be a major advantage. A novel method for intraoperative margin assessment was developed by applying a thin flexible scintillating film to specimens—flexible autoradiography (FAR) imaging. A single-arm, multi-centre study was conducted to evaluate the feasibility of intraoperative [18F]FDG FAR for the assessment of tumour margins in BCS.MethodsEighty-eight patients with invasive breast cancer undergoing BCS received ≤ 300 MBq of [18F]FDG 60–180 min pre-operatively. Following surgical excision, intraoperative FAR imaging was performed using the LightPath® Imaging System. The first 16 patients were familiarisation patients; the remaining 72 patients were entered into the main study. FAR images were analysed post-operatively by three independent readers. Areas of increased signal intensity were marked, mean normalised radiances and tumour-to-tissue background (TBR) determined, agreement between histopathological margin status and FAR assessed and radiation dose to operating theatre staff measured. Subgroup analyses were performed for various covariates, with thresholds set based on ROC curves.ResultsData analysis was performed on 66 patients. Intraoperative margin assessment using FAR was completed on 385 margins with 46.2% sensitivity, 81.7% specificity, 8.1% PPV, 97.7% NPV and an overall accuracy of 80.5%, detecting both invasive carcinoma and DCIS. A subgroup analysis based on [18F]FDG activity present at time of imaging revealed an increased sensitivity (71.4%), PPV (9.3%) and NPV (98.4%) in the high-activity cohort with mean tumour radiance and TBR of 126.7 ± 45.7 photons/s/cm2/sr/MBq and 2.1 ± 0.5, respectively. Staff radiation exposure was low (38.2 ± 38.1 µSv).Conclusion[18F]FDG FAR is a feasible and safe technique for intraoperative tumour margin assessment. Further improvements in diagnostic performance require optimising the method for scintillator positioning and/or the use of targeted radiopharmaceuticals.Trial registration: Identifier: NCT02666079. Date of registration: 28 January 2016. URL: https://clinicaltrials.gov/ct2/show/NCT02666079.ISRCTN registry: Reference: ISRCTN17778965. Date of registration: 11 February 2016. URL: http://www.isrctn.com/ISRCTN17778965.

Optical palpation for tumor margin assessment in breast-conserving surgery.

Intraoperative margin assessment is needed to reduce the re-excision rate of breast-conserving surgery. One possibility is optical palpation, a tactile imaging technique that maps stress (force applied across the tissue surface) as an indicator of tissue stiffness. Images (optical palpograms) are generated by compressing a transparent silicone layer on the tissue and measuring the layer deformation using optical coherence tomography (OCT). This paper reports, for the first time, the diagnostic accuracy of optical palpation in identifying tumor within 1 mm of the excised specimen boundary using an automated classifier. Optical palpograms from 154 regions of interest (ROIs) from 71 excised tumor specimens were obtained. An automated classifier was constructed to predict the ROI margin status by first choosing a circle diameter, then searching for a location within the ROI where the circle was ≥ 75% filled with high stress (indicating a positive margin). A range of circle diameters and stress thresholds, as well as the impact of filtering out non-dense tissue regions, were tested. Sensitivity and specificity were calculated by comparing the automated classifier results with the true margin status, determined from co-registered histology. 83.3% sensitivity and 86.2% specificity were achieved, compared to 69.0% sensitivity and 79.0% specificity obtained with OCT alone on the same dataset using human readers. Representative optical palpograms show that positive margins containing a range of cancer types tend to exhibit higher stress compared to negative margins. These results demonstrate the potential of optical palpation for margin assessment.

Analysis of sensitivity in quantitative micro-elastography.

Quantitative micro-elastography (QME), a variant of compression optical coherence elastography (OCE), is a technique to image tissue elasticity on the microscale. QME has been proposed for a range of applications, most notably tumor margin assessment in breast-conserving surgery. However, QME sensitivity, a key imaging metric, has yet to be systematically analyzed. Consequently, it is difficult to optimize imaging performance and to assess the potential of QME in new application areas. To address this, we present a framework for analyzing sensitivity that incorporates the three main steps in QME image formation: mechanical deformation, its detection using optical coherence tomography (OCT), and signal processing used to estimate elasticity. Firstly, we present an analytical model of QME sensitivity, validated by experimental data, and demonstrate that sub-kPa elasticity sensitivity can be achieved in QME. Using silicone phantoms, we demonstrate that sensitivity is dependent on friction, OCT focus depth, and averaging methods in signal processing. For the first time, we show that whilst lubrication of layer improves accuracy by reducing surface friction, it reduces sensitivity due to the time-dependent effect of lubricant exudation from the layer boundaries resulting in increased friction. Furthermore, we demonstrate how signal processing in QME provides a trade-off between sensitivity and resolution that can be used to optimize imaging performance. We believe that our framework to analyze sensitivity can help to sustain the development of QME and, also, that it can be readily adapted to other OCE techniques.

Effect of Intraoperative Imprint Cytology Followed by Frozen Section on Margin Assessment in Breast-Conserving Surgery.

Intraoperative margin assessment can reduce positive margins in patients undergoing breast-conserving surgery. However, reports on intraoperative margin assessment have described only the use of either imprint cytology or frozen section. This study was designed to elucidate the effect of intraoperative margin assessment using imprint cytology followed by frozen section. Overall, 522 patients were enrolled. First, the entire surgical margin was subjected to imprint cytology. Frozen section was performed only in cases with "positive" or "suspicious" imprint cytology results. An additional intraoperative excision was performed in patients with frozen section-positive lesion sites. All margins were evaluated using postoperative permanent sections after excision. Among 522 patients, 136 (26.1%) were imprint cytology-positive, and 386 (73.9%) were imprint cytology-negative. Among the 386 imprint cytology-negative patients not subjected to frozen section, 11 (2.1%) were permanent sections-positive (imprint cytology-false-negative). In 47 of the 136 imprint cytology-positive patients, additional intraoperative excision was unnecessary due to the frozen section-negative diagnosis. Moreover, these patients could avoid reoperation, because they were permanent section-negative. The false-positive rate of imprint cytology alone was 13.4%, but adding frozen section to imprint cytology decreased the overall false-positive rate to 2.5%. After undergoing excision, four patients still had positive margins. The overall positive margin rate in the final pathology based on permanent sections was 2.9% (15/522). Imprint cytology followed by frozen section led to a markedly decreased positive margin rate. This is considered the best method for intraoperative margin assessment, as it can overcome the limitations of cytology and histology performed individually.

Diagnostic Accuracy of Quantitative Micro-Elastography for Margin Assessment in Breast-Conserving Surgery.

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)-based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS. SIGNIFICANCE: An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery.

Emerging Technologies for Real-Time Intraoperative Margin Assessment in Future Breast-Conserving Surgery.

Clean surgical margins in breast‐conserving surgery (BCS) are essential for preventing recurrence. Intraoperative pathologic diagnostic methods, such as frozen section analysis and imprint cytology, have been recognized as crucial tools in BCS. However, the complexity and time‐consuming nature of these pathologic procedures still inhibit their broader applicability worldwide. To address this situation, two issues should be considered: 1) the development of nonpathologic intraoperative diagnosis methods that have better sensitivity, specificity, speed, and cost; and 2) the promotion of new imaging algorithms to standardize data for analyzing positive margins, as represented by artificial intelligence (AI), without the need for judgment by well‐trained pathologists. Researchers have attempted to develop new methods or techniques; several have recently emerged for real‐time intraoperative management of breast margins in live tissues. These methods include conventional imaging, spectroscopy, tomography, magnetic resonance imaging, microscopy, fluorescent probes, and multimodal imaging techniques. This work summarizes the traditional pathologic and newly developed techniques and discusses the advantages and disadvantages of each method. Taking into consideration the recent advances in analyzing pathologic data from breast cancer tissue with AI, the combined use of new technologies with AI algorithms is proposed, and future directions for real‐time intraoperative margin assessment in BCS are discussed.

Abstract P4-13-03: Effect of intraoperative imprint cytology followed by frozen section for margin assessment in breast-conserving surgery

Abstract Purpose: In patients undergoing breast-conserving surgery (BCS) for breast cancer, the positive margin rate has reportedly reduced from 15%-50% to 6%-19% by the addition of intraoperative margin assessment (IMA). Previous reports have suggested that imprint cytology (IC) is superior to frozen section (FS) because the former can assess the entire circumference of surgical margins, although its precision is inferior to that of FS. In contrast, FS cannot evaluate the entire circumference of surgical margins and may result in sampling errors in the detection of positive margins. To date, reports on IMA have described only the single use of IC or FS. Therefore, the purpose of the present study was to elucidate the effect of IC followed by FS for IMA in BCS by comparing the positive margin rate with that of permanent section (PS). Patients and Methods: We enrolled a total of 522 cases which underwent BCS without neoadjuvant therapy between January 2013 and April 2019. The entire circumference of surgical margins was subjected to IC. Upon obtaining negative IC results, no other procedure was added for IMA. FS was only added for the cases with “positive” or “suspicious” IC results. We performed additional intraoperative excision for FS-positive sites of lesions and did not add any procedure for IMA. All margins were evaluated by postoperative PS after excision. We defined “PS positive” as the exposure of cancer cell for invasive ductal carcinoma and close margin less than 2 mm for non-invasive ductal carcinoma (DCIS) based on the Society of Surgical Oncology and American Society of Radiation Oncology guidelines (2014/2016). Cases diagnosed as IC positive but not subjected to additional intraoperative excision based on FS-negative findings were defined as “IC false positive.” We then compared the results of PS with those of IC and FS. In addition, we evaluated the association between clinicopathological factors and PS-positive or IC-false-positive diagnosis by univariate and multivariate analyses. Results: Of 522 cases, 136 (26.1%) were IC positive and 386 (73.9%) were IC negative. Among the 386 cases not subjected to FS for IMA because of IC-negative diagnosis, 11 (2.8%) were PS positive. In 47 (34.6%) of 136 IC-positive cases, additional intraoperative excision was unnecessary due to FS-negative diagnosis. Postoperative PS revealed that all of these 47 cases were PS negative. Although we performed additional intraoperative excision, 5 cases remained PS positive. There was no association between PS-positive diagnosis and clinicopathological factors. In univariate analysis, premenopausal status and DCIS significantly increased the IC-false-positive diagnosis risk (p &amp;lt; 0.0001 and p = 0.014, respectively). Multivariable analysis revealed that premenopause was a significant risk factor for IC-false-positive diagnosis (OR: 0.27, 95% CI: 0.13-0.56; p&amp;lt; 0.001). The overall positive margin rate on final pathology based on PS was 3.1% (16/522 cases). Conclusion: The proposed method is the best method to compensate for the individual weak points of IC and FS. Because upon finding margin-positive lesions on IC, FS were added to the lesions. Our findings indicate that the proposed strategy should be an optimal method for taking advantages of both IC and FS. As a result, the positive margin rate using our strategy was extremely low compared with that reported in previous studies. Citation Format: Tamaki Tamanuki, Maki Namura, Tomoyoshi Aoyagi, Tomoko Suwa, Shinichirou Shimizu, Hiroshi Matsuzaki. Effect of intraoperative imprint cytology followed by frozen section for margin assessment in breast-conserving surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-03.

Abstract P3-13-04: 18F-FDG micro-PET/CT for intraoperative margin assessment in breast conserving surgery using: A proof-of-concept study

Abstract Positive surgical margins represent a high risk for adverse clinical outcome in breast conserving surgery (BCS). Therefore, the goal of BCS is to avoid positive margins and hence avoid reoperation. Unfortunately, most studies currently assess the rate of positive resection margins at 20%. This is in part due to the lack of a time- and cost-effective method for intraoperative margin assessment, which would enable the prediction of positive margins during the initial surgery. We propose to address this problem by performing intraoperative high-resolution 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) with X-ray computed tomography (CT). This method relies on the high sensitivity of FDG-PET for detecting metabolically active tumor tissue, and the delineation of the anatomical margins of the specimen using CT. In this proof-of-concept study we assess the feasibility of this technique. Twenty patients with breast cancer that were eligible to undergo BCS were enrolled in the study after providing informed consent. The study was approved by the Ethics Committee of Ghent University Hospital. Prior to surgery each patient was administered 4 MBq/kg of FDG. Surgery was performed 2-4 hours after tracer administration. Following surgical excision the breast specimen was oriented with sutures and micro-PET/CT images were obtained using the MOLECUBES β-CUBE (PET) and X-CUBE (CT). The scan time was 10 minutes on PET and 3 minutes on CT. The specimen was then sent for histopathological assessment. Micro-PET/CT images were analyzed using an automated algorithm. Briefly, this algorithm defined the contour of the tumor as the region with high FDG uptake and the contour of the specimen based on the CT image. The margin status of a specimen was positive if the distance between the contour of the tumor and specimen was 0 mm. Images were also analyzed postoperatively by two surgeons blinded to the histopathological and algorithm analysis results. The sensitivity and specificity of the proposed method were then calculated by comparing to the histopathological results, which is the gold standard for margin status assessment. In all samples a region with high FDG uptake was visualized, which corresponded to the tumor on histopathological. In one specific case a small satellite lesion with high FDG uptake, 3 mm in diameter, was detected on the micro-PET images at a distance from the main tumor. Histopathological confirmed that this previously undetected lesion was a second invasive carcinoma. For margin status, a sensitivity of 75% and specificity of 75% were obtained using automated algorithm analysis. Sensitivity and specificity obtained based on surgeons' analysis was 62,5% and 75% for surgeon A and 87,5% and 91,7% for surgeon B respectively. Taking into account the intra-operative micro-PET results could theoretically have reduced the reoperation rate by 75%. This proof-of-concept study demonstrates that high-resolution intraoperative FDG-PET/CT is a promising technique for intraoperative margin assessment in BCS that could allow to reduce re-excision rate. This technique achieves both sufficient sensitivity and specificity with minimal disruption of intraoperative workflow. Citation Format: Marcinkowski R, Keereman V, Van Holen R, Vandenberghe S, Van Bockstal M, Van Dorpe J, Brans B, Goker M, Depypere H, Van den Broecke R. 18F-FDG micro-PET/CT for intraoperative margin assessment in breast conserving surgery using: A proof-of-concept study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-13-04.

Intraoperative Specimen Mammography for Margin Assessment in Breast-Conserving Surgery.

The purpose of this study aimed to determine whether intraoperative specimen mammography is an effective margin assessment method in Asian women. Thus, 182 patients who underwent breast-conserving surgery (BCS) were evaluated. After wide excision, intraoperative specimen mammography was used to assess margin adequacy. The control group comprised 84 patients who underwent BCS and were evaluated for margin of frozen section during surgery. 61.6% patients had dense breasts and 85.7% of dense breasts could margin assess by intraoperative specimen mammography. There were no significant differences in the incidence of extremely close margins (p = 0.421) and second operation (p = 0.252) between both groups. Significant correlations were found between radiological and histological margins (R2 = 0.222, p < 0.05). The frozen section analysis group had longer operative time than the specimen mammography group. The study results show that intraoperative specimen mammography of breast lesions in BCS is useful in identifying margin clearance.

Micro-computed tomography (micro-CT) for intraoperative surgical margin assessment of breast cancer: A feasibility study in breast conserving surgery

PurposeAround 15%–30% of patients receiving breast-conserving surgery (BCS) for invasive breast carcinoma or ductal carcinoma in situ (DCIS) need a reoperation due to tumor-positive margins at final histopathology. Currently available intraoperative surgical margin assessment modalities all have specific limitations. Therefore, we aimed to assess the feasibility and accuracy of micro-computed tomography (micro-CT) as a novel method for intraoperative margin assessment in BCS. MethodsLumpectomy specimens from 30 consecutive patients diagnosed with invasive breast cancer or DCIS were imaged using a micro-CT. Margin status was assessed on micro-CT images by two investigators who were blinded to the final histopathological margin status. The micro-CT margin status was compared with the histopathological margin status. ResultsThe margin status could be assessed by micro-CT in 29 out of 30 patients. Of these, nine patients had a positive tumor margin and 20 a negative tumor margin at final histopathology. Margin status evaluation by micro-CT took always less than 15 min. The margin status in 25 patients was correctly predicted by micro-CT. There were four false-negative predictions. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of micro-CT in margin status prediction were 86%, 56%, 100%, 100% and 83%, respectively. With micro-CT, the positive margin rate could potentially have been reduced from 31% to 14%. ConclusionsWhole lumpectomy specimen micro-CT scanning is a promising technique for intraoperative margin assessment in BCS. Intraoperative quick feedback on the margin status could potentially lead to a reduction in the number of reoperations.

Depth-encoded optical coherence elastography for simultaneous volumetric imaging of two tissue faces.

Depth-encoded optical coherence elastography (OCE) enables simultaneous acquisition of two three-dimensional (3D) elastograms from opposite sides of a sample. By the choice of suitable path-length differences in each of two interferometers, the detected carrier frequencies are separated, allowing depth-ranging from each interferometer to be performed simultaneously using a single spectrometer. We demonstrate depth-encoded OCE on a silicone phantom and a freshly excised sample of mouse liver. This technique minimizes the required spectral detection hardware and halves the total scan time. Depth-encoded OCE may expedite clinical translation in time-sensitive applications requiring rapid 3D imaging of multiple tissue surfaces, such as tumor margin assessment in breast-conserving surgery.