Re-excision Procedures Research Articles

Structured illumination microscopy for cancer identification in diagnostic breast biopsies.

Breast cancer is the second most common cancer diagnosed in women in the US with almost 280,000 new cases anticipated in 2023. Currently, on-site pathology for location guidance is not available during the collection of breast biopsies or during surgical intervention procedures. This shortcoming contributes to repeat biopsy and re-excision procedures, increasing the cost and patient discomfort during the cancer management process. Both procedures could benefit from on-site feedback, but current clinical on-site evaluation techniques are not commonly used on breast tissue because they are destructive and inaccurate. Ex-vivo microscopy is an emerging field aimed at creating histology-analogous images from non- or minimally-processed tissues, and is a promising tool for addressing this pain point in clinical cancer management. We investigated the ability structured illumination microscopy (SIM) to generate images from freshly-obtained breast tissues for structure identification and cancer identification at a speed compatible with potential on-site clinical implementation. We imaged 47 biopsies from patients undergoing a guided breast biopsy procedure using a customized SIM system and a dual-color fluorescent hematoxylin & eosin (H&E) analog. These biopsies had an average size of 0.92 cm2 (minimum 0.1, maximum 4.2) and had an average imaging time of 7:29 (minimum 0:22, maximum 37:44). After imaging, breast biopsies were submitted for standard histopathological processing and review. A board-certified pathologist returned a binary diagnostic accuracy of 96% when compared to diagnoses from gold-standard histology slides, and key tissue features including stroma, vessels, ducts, and lobules were identified from the resulting images.

Does Nipple-Ward Positive Margin Contribute to a Higher Rate of Re-Excision Procedures After a Lumpectomy with Pathology-Confirmed Positive Margins? A Retrospective Study.

Positive margins on lumpectomy specimens are associated with a twofold increased risk of local breast tumor recurrence. Prior literature has demonstrated various techniques and modalities for assessing margin status to reduce re-excision rates. However, there is paucity of literature analyzing which margin contributes to the highest re-excision rates. Therefore, the primary aim of the study was to investigate whether the nipple-ward margins resulted in a higher rate of re-excision in our patient population. A retrospective chart review was performed on patients who had re-excision surgery. Nipple-ward margin was identified by correlating radiological and pathological reports. A cut-off of more than 25% was used to demonstrate correlation between nipple-ward margin and re-excision rate. A total of 98 patients' data were analyzed, with 41 (41.8%), 14 (14.3%), 5 (5.1%), and 38 (38.8%) diagnosed with DCIS, IDC, ILC, and mixed pathology on their margins, respectively. Overall, 48% (n=47) of the positive margins were nipple-ward, with 44.7% (n=21) reporting DCIS. Upon stratification, 45 (45.9%) cases were single-margin positive, with 26 (57.8%) being nipple-ward. Furthermore, the remaining 53 (54.1%) patients had multiple positive margins, with 21 (39.6.7%) nipple-ward cases. Positive nipple-ward margins significantly contribute to a higher re-excision rate p < 0.001; 48% of re-excision surgeries had positive nipple-ward margins, and 57.8% of positive single-margin cases were nipple-ward. Taking an additional shave during initial lumpectomy decreases re-excision rates. However, planning a lumpectomy procedure with a more elliptical rather than a spherical resection with additional cavity shave (ie, larger volume) in the nipple-ward direction and minimizing the remaining cavity shaves so the total volume resected remains unchanged. Nevertheless, future studies with larger sample sizes are required to bolster our findings.

Breast-Conserving Surgery Margin Guidance Using Micro-Computed Tomography: Challenges When Imaging Radiodense Resection Specimens.

Breast-conserving surgery (BCS) is an integral component of early-stage breast cancer treatment, but costly reexcision procedures are common due to the high prevalence of cancer-positive margins on primary resections. A need exists to develop and evaluate improved methods of margin assessment to detect positive margins intraoperatively. A prospective trial was conducted through which micro-computed tomography (micro-CT) with radiological interpretation by three independent readers was evaluated for BCS margin assessment. Results were compared to standard-of-care intraoperative margin assessment (i.e., specimen palpation and radiography [abbreviated SIA]) for detecting cancer-positive margins. Six hundred margins from 100 patients were analyzed. Twenty-one margins in 14 patients were pathologically positive. On analysis at the specimen-level, SIA yielded a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 42.9%, 76.7%, 23.1%, and 89.2%, respectively. SIA correctly identified six of 14 margin-positive cases with a 23.5% falsepositive rate (FPR). Micro-CT readers achieved sensitivity, specificity, PPV, and NPV ranges of 35.7-50.0%, 55.8-68.6%, 15.6-15.8%, and 86.8-87.3%, respectively. Micro-CT readers correctly identified five to seven of 14 margin-positive cases with an FPR range of 31.4-44.2%. If micro-CT scanning had been combined with SIA, up to three additional margin-positive specimens would have been identified. Micro-CT identified a similar proportion of margin-positive cases as standard specimen palpation and radiography, but due to difficulty distinguishing between radiodense fibroglandular tissue and cancer, resulted in a higher proportion of falsepositive margin assessments.

Abstract P3-18-11: Meeting the challenge of successful one-stage lumpectomy for DCIS

Abstract Introduction: Positive lumpectomy margins are associated with an increased risk for ipsilateral tumor recurrence, and necessitate additional procedures to achieve acceptable margins. Re-excision rates are higher in patients with ductal carcinoma in situ (DCIS) versus those with invasive carcinoma. The purpose of this study was to investigate the clinicopathologic characteristics, surgical techniques, and other outcomes associated with re-excision over time following primary breast conserving surgery for DCIS. Methods: Our institutional Breast Cancer Database was queried for patients treated with lumpectomy as the primary procedure for pure DCIS from 2010-2021. Cases of microinvasive disease were excluded. The primary endpoint was the rate of re-excision following lumpectomy. Variables of interest included patient demographics and clinicopathologic characteristics. As a secondary analysis, adjusted odds ratios for the association of MarginProbe® with re-excisions were calculated using a multivariable logistic regression model controlling for age, tumor size, breast density and DCIS subtype. Individual comparisons of continuous variables were based on t-tests, group proportions compared with one-way ANOVA, and categorical variables compared using Chi Square tests. Results: Out of a total of 695 patients in our cohort, 221 (32%) had re-excisions. There was a statistically significant 2% decline per year in the number of re-excisions (p=0.005). Patients who underwent re-excision had larger size of DCIS (2.37 cm vs 1.37 cm, p&amp;lt;0.001). Papillary-type DCIS was associated with an increased rate of re-excision surgery (Table 1). Prior to the introduction of the MarginProbe® for intraoperative margin assessment in 2014, approximately 42% of patients with DCIS underwent re-excisions. This decreased to 24.9% in the post-2013 time frame (p=0.02). In an unadjusted estimate for the odds ratio for association, patients who underwent lumpectomy with MarginProbe® were 81% less likely to require re-excision (OR = 0.19, 95% CI = 0.12, 0.31, p&amp;lt;0.0001). In a logistic regression model controlling for potential confounders with re-excision as the dependent variable and MarginProbe® as the primary explanatory variable, patients for whom the MarginProbe® was used were 66% less likely to require re-excision when controlling for age, tumor size, menopausal status, breast density, and pathology (OR = 0.34, 95% CI 0.16, 0.69). Of patients who required re-excision, 20% went on to mastectomies as their second procedure. After each unsuccessful re-excision, a larger proportion of patients converted to mastectomy. In total, 26% of patients who had unsuccessful primary surgery went on to mastectomies. Of patients who proceeded to mastectomy as their second procedures, 13% were found to carry BRCA1 or 2 mutations. Conclusions: In our study of patients diagnosed with pure DCIS and treated with primary breast conserving surgery, larger size of DCIS and papillary subtype were associated with an increased rate of re-excision procedures. A proportion of patients with unsuccessful primary lumpectomies required multiple procedures to complete their surgical treatment and 26% went on to mastectomy. Patients whose primary procedures included intraoperative margin assessment with the MarginProbe® were significantly less likely to require re-excision. Intraoperative margin assessment is an important tool that can support breast conserving surgery in the challenging population of patients with DCIS. Table 1.Clinicopathologic CharacteristicsVariableNo Re-excision (n=313)Re-Excision (n=100)P-ValueAge; mean (SD)61.48 (12.01)58.04 (13.39)0.016Age of Menopause; mean (SD)50.22 (5.18)48.13 (5.45)0.004Size of DCIS; mean (SD)1.37 (1.25)2.37 (2.00)&amp;lt;0.001Breast Density (%)0.149N/A6 (1.9)2 (2.0)Entirely Fatty10 (3.2)3 (3.0)Extremely Dense19 (6.1)13 (13.0)Heterogeneously Dense165 (52.7)42 (42.0)Scattered Fibroglandular113 (36.1)40 (4.0)DCIS SubtypePapillary93 (29.7)48 (48.0)0.001Cribiform206 (65.8)69 (69.0)0.641Solid190 (60.7)60 (60.0)0.994Comedo54 (17.3)25 (25.0)0.117Surgical Margins (%)&amp;lt;0.001Close (&amp;gt;0 and &amp;lt;1mm)3 (1.0)60 (60.0)Negative (≥1 mm)310 (99.0)13 (13.0)Positive (≤0 mm)0 (0.0)27 (27.0) Citation Format: Joshua A Feinberg, Charles DiMaggio, Nakisa Pourkey, Jennifer Chun Kim, Jenny Goodgal, Amber Guth, Deborah Axelrod, Freya Schnabel. Meeting the challenge of successful one-stage lumpectomy for DCIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-11.

Optical scatter imaging of resected breast tumor structures matches the patterns of micro-computed tomography

In patients undergoing breast-conserving surgery (BCS), the rate of re-excision procedures to remove residual tumor left behind after initial resection can be high. Projection radiography, and recently, volumetric x-ray imaging are used to assess margin adequacy, but x-ray imaging lacks contrast between healthy, abnormal benign, and malignant fibrous tissues important for surgical decision making. The purpose of this study was to compare micro-CT and optical scatter imagery of surgical breast specimens and to demonstrate enhanced contrast-to intra-tumoral morphologies and tumor boundary features revealed by optical scatter imaging. A total of 57 breast tumor slices from 57 patients were imaged ex vivo by spatially co-registered micro-CT and optical scatter scanning. Optical scatter exhibited greater similarity with micro-CT in 89% (51/57) of specimens versus diffuse white light (DWL) luminance using mutual information (mean ± standard deviation of 0.48 ± 0.21 versus 0.24 ± 0.12; p < 0.001) and in 81% (46/57) of specimens using the Sørensen–Dice coefficient (0.48 ± 0.21 versus 0.33 ± 0.18; p < 0.001). The coefficient of variation (CV) quantified the feature content in each image. Optical scatter exhibited the highest CV in every specimen (optical scatter: 0.70 ± 0.17; diffuse luminance: 0.24 ± 01; micro-CT: 0.15 ± 0.03 for micro-CT; p < 0.001). Optical scatter also exhibited the highest contrast ratios across representative tumor boundaries with adjacent healthy/benign fibrous tissues (1.5–3.7 for optical scatter; 1.0–1.1 for diffuse luminance; 1.0–1.1 for micro-CT). The two main findings from this study were: first, optical scatter contrast was in general similar to the radiological view of the tissue relative to DWL imaging; and second, optical scatter revealed additional features associated with fibrous tissue structures of similar radiodensity that may be relevant to diagnosis. The value of micro-CT lies in its rapid three-dimensional scanning of specimen morphology, and combined with optical scatter imaging with sensitivity to fibrous surface tissues, may be an attractive solution for margin assessment during BCS.

Regenerative tissue filler for breast conserving surgery and other soft tissue restoration and reconstruction needs

Complete removal of cancerous tissue and preservation of breast cosmesis with a single breast conserving surgery (BCS) is essential for surgeons. New and better options would allow them to more consistently achieve this goal and expand the number of women that receive this preferred therapy, while minimizing the need for re-excision and revision procedures or more aggressive surgical approaches (i.e., mastectomy). We have developed and evaluated a regenerative tissue filler that is applied as a liquid to defects during BCS prior to transitioning to a fibrillar collagen scaffold with soft tissue consistency. Using a porcine simulated BCS model, the collagen filler was shown to induce a regenerative healing response, characterized by rapid cellularization, vascularization, and progressive breast tissue neogenesis, including adipose tissue and mammary glands and ducts. Unlike conventional biomaterials, no foreign body response or inflammatory-mediated “active” biodegradation was observed. The collagen filler also did not compromise simulated surgical re-excision, radiography, or ultrasonography procedures, features that are important for clinical translation. When post-BCS radiation was applied, the collagen filler and its associated tissue response were largely similar to non-irradiated conditions; however, as expected, healing was modestly slower. This in situ scaffold-forming collagen is easy to apply, conforms to patient-specific defects, and regenerates complex soft tissues in the absence of inflammation. It has significant translational potential as the first regenerative tissue filler for BCS as well as other soft tissue restoration and reconstruction needs.

Savi Scout® Radar Localisation of Non-palpable Breast Lesions: Systematic Review and Pooled Analysis of 842 Cases.

With the increase in detection of non-palpable breast lesions through screening, wire-guided localisation (WGL) has long been the favoured method for preoperative localisation. However, this technique comes with several limitations. New methods have been developed, including several non-radioactive, wireless options. We aimed to assess the effectiveness of Savi Scout® localisation (SSL) through this pooled analysis and systematic review. A number of databases were searched for records reporting data on localisation and retrieval of SSL reflectors, as well as re-excision rate. We included our own data from 20 patients (22 reflectors) at our institution. A total of 842 reflectors were inserted across eleven studies and our own data. Pooled analysis revealed an overall successful deployment rate of 99.64% and a successful retrieval rate of 99.64% using SSL. A statistically significant difference in re-excision rate was found in a smaller pooled analysis conducted across four studies comparing SSL and WGL (12.9% and 21.1% respectively, p<0.01). The Savi Scout® localisation system is a safe and effective alternative to WGL. It facilitates flexible scheduling by decoupling radiology and surgery interventions and may reduce the need for re-excision procedures for positive surgical margins.

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

Identifying the factors that influence surgeon's compliance with excisional margins of non-melanoma skin cancer.

The rising incidence of Non Melanoma Skin Cancers (NMSC) leads to a high number of surgical procedures worldwide. The strict compliance with international guidelines with regard to excisional margins may help decrease the number of re-excision procedures and reduce the risk of NMSC recurrence. The aim of this study was to investigate the prevalence of excisional margins as recommended by the European Academy of Dermatology and Venereology (EADV) and the European Dermatology Forum (EDF) guidelines, and the factors (demographic or clinical) that influence surgeons’ compliance with these guidelines.This was a prevalence study looking at surgical excisions of NMSCs performed over a period of 2 years (2011–2012). A sample size of 1669 patients was considered. Definition of excisional margins recommended by the international guidelines (EADV and EDF) were used as point of reference for the analysis. Tumor and histologic specimen size were calculated ex vivo by 5 different pathologists. The size of skin specimens was measured with a major axis and a minor axis. The same was done for the tumor present on the skin specimens. The differences between the major and minor axes of surgical specimen and tumor were calculated. These differences were subsequently divided by two, hypothesizing that the lesion had the same distance from the margins of the surgical specimen.The differences obtained were named “Delta”, the formulas applied being the following:Delta major = (major axis specimen—major axis tumor)/2; Delta minor = (minor axis specimen—minor axis tumor)/2.Results show a significant statistical difference, associated with factors such as: age of the patient, anatomical localization of the tumor, histological diagnosis, and surgeons’ experience.The identification of these factors sheds light on clinicians’ practice and decision-making regarding excisional margins. Hopefully a higher level of adherence to the guidelines can be achieved in the future.

Raman-Encoded Molecular Imaging with Topically Applied SERS Nanoparticles for Intraoperative Guidance of Lumpectomy

Intraoperative identification of carcinoma at lumpectomy margins would enable reduced re-excision rates, which are currently as high as 20% to 50%. Although imaging of disease-associated biomarkers can identify malignancies with high specificity, multiplexed imaging of such biomarkers is necessary to detect molecularly heterogeneous carcinomas with high sensitivity. We have developed a Raman-encoded molecular imaging (REMI) technique in which targeted nanoparticles are topically applied on excised tissues to enable rapid visualization of a multiplexed panel of cell surface biomarkers at surgical margin surfaces. A first-ever clinical study was performed in which 57 fresh specimens were imaged with REMI to simultaneously quantify the expression of four biomarkers HER2, ER, EGFR, and CD44. Combined detection of these biomarkers enabled REMI to achieve 89.3% sensitivity and 92.1% specificity for the detection of breast carcinoma. These results highlight the sensitivity and specificity of REMI to detect biomarkers in freshly resected tissue, which has the potential to reduce the rate of re-excision procedures in cancer patients. Cancer Res; 77(16); 4506-16. ©2017 AACR.

Positive Margin Re-Excision Following Immediate Autologous Breast Reconstruction: Morbidity, Cosmetic Outcome, and Oncologic Significance.

Acquisition of negative resection margins is paramount in the surgical management of operable breast cancer. Management of positive margins following mastectomy and immediate breast reconstruction is presently poorly defined. The present study aims at defining morbidity and cosmetic sequela of re-excision procedures aimed at clearing involved mastectomy margins in the setting of immediate autologous breast reconstruction. Oncologic outcomes are recorded. A retrospective study of patients that underwent skin-sparing mastectomy followed by immediate deep inferior epigastric perforator flap breast reconstruction was performed. Patients found to have positive mastectomy margins underwent margin re-excision during a separate procedure. Method of positive margin exposure and resection is described. Flap morbidity and cosmetic outcome following margin re-excision was compared between reconstructed breasts that underwent re-excision vs those reconstructed after prophylactic mastectomy (controls). Cancer recurrence was recorded during the follow-up period. Thirty-six (2.5%) out of 1443 patients were found to have positive mastectomy margins following immediate breast reconstruction between May 2007 and November 2012. Location of positive margins was evenly distributed in all breast regions. Although flap morbidity was similar, a trend (P > 0.05) toward higher seroma formation and fat necrosis was reported in breasts following re-excision vs controls. With a mean follow-up period of 28 months, cosmetic outcome between breasts that underwent re-excision vs controls were similar. Cancer recurrence was reported in 3 (8.3%) patients. Re-excision of positive mastectomy margins following immediate autologous breast reconstruction requires a multidisciplinary approach and may be performed with minimal additional morbidity while preserving optimal cosmetic outcome. 3.

Optimizing fresh specimen staining for rapid identification of tumor biomarkers during surgery.

Rationale: Positive margin status due to incomplete removal of tumor tissue during breast conserving surgery (BCS) is a prevalent diagnosis usually requiring a second surgical procedure. These follow-up procedures increase the risk of morbidity and delay the use of adjuvant therapy; thus, significant efforts are underway to develop new intraoperative strategies for margin assessment to eliminate re-excision procedures. One strategy under development uses topical application of dual probe staining and a fluorescence imaging strategy termed dual probe difference specimen imaging (DDSI). DDSI uses a receptor-targeted fluorescent probe and an untargeted, spectrally-distinct fluorescent companion imaging agent topically applied to fresh resected specimens, where the fluorescence from each probe is imaged and a normalized difference image is computed to identify tumor-target distribution in the specimen margins. While previous reports suggested this approach is a promising new tool for surgical guidance, advancing the approach into the clinic requires methodical protocol optimization and further validation.Methods: In the present study, we used breast cancer xenografts and receiver operator characteristic (ROC) curve analysis to evaluate a wide range of staining and imaging parameters, and completed a prospective validation study on multiple tumor phenotypes with different target expression. Imaging fluorophore-probe pair, concentration, and incubation times were systematically optimized using n=6 tissue specimen replicates per staining condition. Resulting tumor vs. normal adipose tissue diagnostic performance were reported and staining patterns were validated via receptor specific immunohistochemistry colocalization. Optimal staining conditions were tested in receptor positive and receptor negative cohorts to confirm specificity.Results: The optimal staining conditions were found to be a one minute stain in a 200 nM probe solution (area under the curve (AUC) = 0.97), where the choice of fluorescent label combination did not significantly affect the diagnostic performance. Using an optimal threshold value determined from ROC curve analysis on a training data set, a prospective study on xenografts resulted in an AUC=0.95 for receptor positive tumors and an AUC = 0.50 for receptor negative (control) tumors, confirming the diagnostic performance of this novel imaging technique.Conclusions: DDSI provides a robust, molecularly specific imaging methodology for identifying tumor tissue over benign mammary adipose tissue. Using a dual probe imaging strategy, nonspecific accumulation of targeted probe was corrected for and tumor vs. normal tissue diagnostic potential was improved, circumventing difficulties with ex vivo tissue specimen staining and allowing for rapid clinical translation of this promising technology for tumor margin detection during BCS procedures.

The impact of use of an intraoperative margin assessment device on re-excision rates.

Historically there has been a high rate of surgical interventions to obtain clear margins for breast cancer patients undergoing breast conserving local therapy. An intraoperative margin assessment tool (MarginProbe) has been approved for use in the US since 2013. This study is the first compilation of data from routine use of the device, to assess the impact of device utilization on re-excision rates. We present a retrospective, observational, review from groups of consecutive patients, before and after the implementation of intraoperative use of the device during lumpectomy procedures. Lesions were localized by standard methods. The intraoperative margin assessment device was used on all circumferential margins of the main specimen, but not on any additional shavings. A positive reading by the device led to an additional shaving of the corresponding cavity location. Specimens were also, when feasible, imaged intra-operatively by X-ray, and additional shavings were taken if needed based on clinical assessment. For each surgeon, historical re-excision rates were established based on a consecutive set of patients from a time period proximal to initiation of use of the device. From March 2013 to April 2014 the device was routinely used by 4 surgeons in 3 centers. In total, 165 cases lumpectomy cases were performed. Positive margins resulted in additional re-excision procedures in 9.7% (16/165) of the cases. The corresponding historical set from 2012 and 2013 consisted of 186 Lumpectomy cases, in which additional re-excision procedures were performed in 25.8% (48/186) of the cases. The reduction in the rate of re-excision procedures was significant 62% (P < 0.0001). Use of an intraoperative margin assessment device contributes to achieving clear margins and reducing re-excision procedures. As in some cases positive margins were found on shavings, future studies of interest may include an analysis of the effect of using the device on the shavings intra-operatively.

Oncoplastic surgery: pushing the limits of breast-conserving surgery.

In recent decades, the surgical management of breast cancer has steadily and considerably improved. Mutilating procedures have given way to more individualized surgical approaches aiming to preserve the breast as much as possible. For large tumors, preoperative chemotherapy is a major tool, but emerging oncoplastic surgery techniques are also a new approach in the armamentarium of breast cancer surgery, as a third option between conventional breast-conserving surgery and mastectomy. As this new treatment modality allows wider margin excision, it reduces the need for re-excision procedures and possibly increases breast conservation rates by extending the indications of breast-conserving surgery. This review will provide an overview of current practices and clinical data available to date on oncoplastic surgery.

Combined experience at three breast centers with routine use of an intraoperative margin assessment device including comparison to historical re-excision rates.

79 Background: Historically there has been a high rate of surgical interventions to obtain clear margins for breast cancer patients undergoing breast conserving local therapy. This study is the first compellation of data among three breast centers to assess the impact of an intraoperative margin assessment tool (MarginProbe) on re-excision rates. This device has been approved for clinical use in the United States since 2013. We present groups of consecutive patients in each of these breast centers – before and after the implementation of routine intraoperative use of the margin assessment device during lumpectomy procedures. Methods: Lesions were localized by standard methods. The intraoperative margin assessment device was used on all circumferential margins of the main specimen, but not on any additional shavings. A positive reading by the device led to an additional shaving of the corresponding cavity location. Specimens were also imaged intra-operatively by X-ray, and additional shavings were taken if needed based on clinical assessment. We established the historical re-excision rates of each surgeon on a consecutive set of patients in a corresponding period just before we began using the device. Results: In total, 165 patients were treated in three institutions up until April 2014. Sixteen patients (9.7%, 16/165) required re-excision. Historical re-excision rates corresponding to periods of use before the intraoperative margin assessment device was put into use were 25.8% (48/186). The re-excision rate was reduced by 62% (P&lt;0.0001). Six re-excisions were due to a positive shaving which was not measured by the device. Conclusions: Use of an intraoperative margin assessment device contributes to achieving clear margins and reducing re-excision procedures. As in some cases positive margins were found on shavings, future studies of interest may include an analysis of the effect of using the device on the shavings intra-operatively.

Intraoperative assessment of margins in breast conservative surgery--still in use?

A positive margin in breast conserving surgery is associated with an increased risk of local recurrence. Failure to achieve clear margins results in re-excision procedures. Methods for intraoperative assessment of margins have been developed, such as frozen section analysis, touch preparation cytology, near-infrared fluorescence optical imaging, x-ray diffraction technology, high-frequency ultrasound, micro-CT, and radiofrequency spectroscopy. In this article, options that might become the method of choice in the future are discussed.

A Randomized Prospective Study of Lumpectomy Margin Assessment with Use of MarginProbe in Patients with Nonpalpable Breast Malignancies

BackgroundThe presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins.MethodsThis multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted.Results In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant.ConclusionsAdjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons’ ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.

Abstract P5-15-02: Beyond the learning curve: Surgical judgment in the approach to breast conserving surgery

Abstract Background: Inadequate lumpectomy margins are associated with an increased risk of ipsilateral breast tumor recurrence in patients undergoing breast conserving surgery for malignant disease. Second surgical procedures are often required to achieve acceptable margins. The purpose of this study was to examine the practice of breast conserving surgery by experienced practitioners, focusing on the approach to margins at the time of primary lumpectomy procedure. Methods: The NYU Langone Medical Center Breast Cancer Database was queried for patients who underwent breast conserving surgery from 1/2010-1/2013 by experienced breast surgeons. Variables of interest, segregated by surgeon, included: characteristics of additional margins taken at primary lumpectomy surgery, re-excision rates, and rates of conversion to mastectomy. Statistical analyses were performed using Pearson's Chi-Square Test, Spearman's correlation, and descriptive analyses. Results: During the study period, 988 patients opted for breast conserving surgery for invasive and intraductal breast cancer, including 260 patients who underwent at least 1 re-excision procedure. We excluded 31 patients who had initial surgery outside of NYU, yielding a study cohort of 229 patients. Stage 0 disease was associated with an increased frequency of re-excision procedures (p&amp;lt;0.0001). Re-excision rates differed widely among surgeons (10-36%). The average number of additional margins excised did not correlate with surgeons’ re-excision rates (p = 0.18). Additional margins taken at primary lumpectomy surgery included both false positives and true positives (Table 1). Of note, the number of false positive margin excisions was double the number of true positives. Patients who went on to mastectomy after unsuccessful primary lumpectomy surgery (45 of a total of 59 who converted to mastectomy) frequently did so based on their preference (19/45 = 42%). However, patients who converted to mastectomy after multiple excisions generally did so out of concern for extent of disease. Conclusions: In our study, patients with pure intraductal carcinoma represented a particular challenge as surgeons’ margin assessment was less accurate than in cases of invasive cancer. Re-excision rates varied by surgeon, and did not correlate with the average number of additional margins taken at the primary lumpectomy procedure. The rate of false positive margins excised exceeded the true positive rate, reflecting the limitations of surgeons’ ability to assess margins intraoperatively. We documented a significant number of patients who opted for conversion to mastectomy after a single unsuccessful lumpectomy procedure, underscoring the need for better methods of intraoperative margin assessment to support the practice of breast conserving surgery. Table 1: Re-excision rates and approach to margins at primary lumpectomy surgerySurgeonPatients undergoing Re-excision - N (%)Avg Additional Margins Taken (per patient) in Primary LumpectomyFalse Positives - N (%)True Positives - N (%)A67 (23%)139 (10%)26 (6%)B53 (10%)4147 (45%)60 (18%)C14 (19%)217 (20%)6 (7%)D11 (31%)01 (1%)3 (5%)E8 (36%)15 (10%)3 (6%)F27 (11%)118 (11%)10 (6%)G20 (15%)335 (29%)26 (22%)H29 (32%)237 (21%)24 (14%)Total229 (16%)2299 (22%)158 (11%) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-02.

Abstract P4-03-01: Analysis of the impact of intraoperative margin assessment with adjunctive use of MARGINPROBE® vs. standard of care on margin status with different definitions of positive margin depth, results from a randomized prospective multi center study

Abstract Background: The current practice of breast conserving surgery (BCS) involves intraoperative margin assessment according to the surgeon's gross assessment and judgment. This intraoperative assessment has been associated with a 20% to 40% reoperation rate to assure negative margins. MarginProbe (Dune Medical Devices, MA, USA) was developed to provide real-time assessment of lumpectomy specimens to evaluate for the presence of disease at the surgical margins. A 21-center international pivotal study was conducted to determine if adjunctive use of MarginProbe can enable surgeons to identify positive margins intraoperatively, resulting in fewer patients who are candidates for re-excision procedures. Results for a 1mm definition of positive margins have been reported previously. We sought to understand the benefit of device use at alternative thresholds. Methods: 664 women with non-palpable lesions undergoing lumpectomy for DCIS and invasive cancer were enrolled and 596 randomized (1:1) in the operating room following standard of care (SOC) lumpectomy. In the device arm, MARGINPROBE was used to assess all surfaces of the lumpectomy specimen and positive readings required additional resections. The device was not used on additional resections. All specimens were examined to verify excision of the target lesion intraoperatively. Pathologists were blinded to study arm. Additional surgeries to re-excise involved margins were performed per each individual site criteria. Patients were followed for 2 months following surgery; additional procedures were documented. Distance from tumor to each margin face was recorded for each patient. Results: Following lumpectomy, the number of patients having positive margins due to failed intraoperative assessment was significantly reduced in the device arm at each potential definition of positive margins. Patients with positive margins after 1st surgeryDepthDevice (%) N = 298Control (%) N = 298p-value0mm6.413.40.00571mm15.438.3&amp;lt;0.00012mm22.549.7&amp;lt;0.00013mm30.957.0&amp;lt;0.00014mm36.661.7&amp;lt;0.00015mm39.966.4&amp;lt;0.0001*excludes positive margins on shavings, as device was only used on the main specimen Conclusions: It has been shown previously that adjunctive use of MARGINPROBE significantly reduced the number of candidates for re-excision at a 1mm definition of positive margins. Based on this analysis, surgeons can expect a substantial reduction in the number of patients with positive margins at definitions from tumor on ink to 5mm. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-03-01.

Improving breast-conserving surgery: A focus on margins.

127 Background: Inadequate lumpectomy margins are associated with an increased risk of ipsilateral recurrence in patients undergoing breast conserving surgery for cancer. Multiple procedures are often required to achieve acceptable margins, increasing the burden to the patient and the health care system, and potentially delaying other adjuvant treatments. A novel device for intraoperative assessment of lumpectomy margins (MarginProbe) has been associated with a 25% reduction in the rate of positive margins at the conclusion of primary lumpectomy surgery. Our aim was to establish a baseline re-excision rate among surgeons and to initiate a follow up study to assess the impact of incorporating this new technology for intraoperative margin assessment. Methods: The NYU Langone Medical Center Breast Cancer Database was queried for patients who underwent breast conserving surgery including ≥ 1 re-excision procedure from 1/2010-1/2013. Variables of interest included re-excision rates, stage of disease, and additional margins taken at primary lumpectomy surgery. Statistical analyses included descriptive analyses and Pearson’s Chi-Square. Results: During the study period 957 patients had breast conserving surgery and 229 required ≥ 1 re-excision procedures (24%). Re-excision rates varied widely among surgeons (10-36%). Stage 0 disease (ductal carcinoma in situ) was associated with an increased frequency of re-excisions (p&lt;0.0001). These parameters will be re-evaluated in patients undergoing breast conserving surgery with adjunctive intraoperative use of the MarginProbe device. Re-excision rates and the accuracy of intraoperative assessment of lumpectomy margins will be compared with the historical cohort. Conclusions: The necessity for multiple surgical procedures to complete breast conserving surgery results in an added burden to the patient and the health care system. Improved intraoperative assessment of lumpectomy margins represents an opportunity to improve the quality of breast cancer surgery. A critical analysis of the impact of a new device on re-excision rates will be important to understand its potential benefit to the conduct of breast conserving surgery.