Redefining Margin Assessment in Breast Conservation Surgery: Surgeon-Performed Intraoperative Ultrasound as a Reliable Alternative to Radiologic and Mammographic Assessment.

Background: Breast-conserving therapy is a long-standing standard surgical procedure for treating breast cancer. The aim is the complete resection of the tumor with free margins to avoid additional surgery and possible relapse. The optimal way to document tumor-free margins intraoperatively is still unclear. Methods: In a retrospective study, we analyzed patients who underwent breast-conserving surgery for the treatment of early breast cancer in our institution. Patients with ductal carcinoma in situ (DCIS), locoregional relapse and those after neoadjuvant chemotherapy were excluded. We investigated the value of intraoperative pathologic evaluation compared with intraoperative specimen mammography for the assessment of tumor-free margins in breast conserving surgery. Results: Between 2009-2022, 465 patients underwent breast conserving surgery and received both intraoperative pathologic evaluation by frozen section and specimen mammography at our institution. The median age of the patients was 62 years. We found 59.1 % of the patients to have an invasive tumor not otherwise specified (NOS), 14.2% to present with an invasive lobular cancer and 18.1% with a mixture of both types, while 8.6% of our patients had another type of tumor, e.g. medullar. Most of the patients, 76.3 %, were node negative and had a tumor stage pT1c. The highest accordance between the results for frozen section and specimen mammography was seen in patients older than 70 years (77.7%), having an invasive breast cancer of no special type (73.8%) and a pT2 tumor stage according to the TNM classification (73.1%). Patients with a hormone-receptor negative tumor had higher accordance rates as well as those with a HER2 positive breast cancer. The difference between the accordance of the two methods was statistically significant only for patients younger than 50 years and those having a G3 tumor. To evaluate the value of the two methods for determining the margin during surgery we calculated the sensitivity, the specificity and the positive predictive value for the specimen radiography as compared to the frozen section resulting in 52.6%, 76.7% and 31.3%, respectively. Conclusion: The intraoperative specimen mammography is not a reliable method to assure tumor free margin for patients undergoing breast conserving surgery. The pathological evaluation of tumor specimen in addition to the specimen mammography resulted in a very low re-excision rate. Only 2.4% of the patients in our cohort had positive margins after complete pathological evaluation postoperatively. While the intraoperative frozen section seems to be the best way to avoid a second surgery, this method is costly and requires the presence of a pathologist. Thus, an improvement of the specimen mammography and the development of new imaging methods are needed. Citation Format: Susanne Briest, Alma Luise Bayer, Laura Weydandt, Mireille Martin, Anne Kathrin Höhn, Ivonne Nel, Bahriye Aktas. Intraoperative assessment of margins in breast conserving therapy: Comparison of intraoperative specimen mammography and intraoperative pathologic evaluation [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-09-13.

Intraoperative margin assessment reduces reexcision rates in patients with ductal carcinoma in situ treated with breast-conserving surgery

Various intraoperative margin assessment techniques have been shown to improve margin status in breast-conserving surgery (BCS) for cancer. Our study sought to evaluate multiple margin assessment techniques on a population level and determine their effects on margin status. Patients undergoing wire-localized BCS for invasive cancer in Alberta, Canada, were assessed using a prospectively entered database of patient and tumor characteristics. Margin status was obtained from chart review. Four margin assessment techniques were studied: specimen mammography (SM), intraoperative ultrasound (US), gross assessment by pathologist (GP), and frozen section analysis (FS). Multivariable logistic regression adjusting for confounders was used to assess effect of any technique on margin status, with secondary analysis evaluating effects of individual techniques. Margin assessment was performed in 1165 of 1649 patients (71%). The overall positive margin rate was 20.8%. Adjusting for confounders, we found no difference in the odds of a positive margin with any margin assessment technique versus wire localization alone (OR 0.79, p=0.22, 95% CI 0.54-1.16). Individually, both GP and FS reduced the risk of a positive margin (GP-OR 0.56, p=0.002, 95% CI 0.39-0.81; FS-OR 0.43, p=0.046, 95% CI 0.19-0.98), whereas SM and US showed no effect (SM-OR 1.23, p=0.29, 95% CI 0.84-1.81; US-OR 1.09, p=0.83, 95% CI 0.50-2.37). Use of any margin assessment technique did not improve margin status compared to wire localization alone. Gross assessment by pathologist and frozen section analysis improved margin status compared to imaging-alone techniques. Further exploration is required to refine optimal margin assessment methods.

BackgroundA surgical margin is the apparently healthy tissue around a tumor which has been removed. In oral cavity carcinoma, a negative margin is considered ≥ 5 mm, a close margin between 1 and 5 mm, and a positive margin ≤ 1 mm. Currently, the intraoperative surgical margin status is based on the visual inspection and tissue palpation by the surgeon and intraoperative histopathological assessment of the resection margins by frozen section analysis (FSA). FSA technique is limited and susceptible to sampling errors. Definitive information on the deep resection margins requires postoperative histopathological analysis.MethodsWe described a novel approach for the assessment of intraoperative surgical margins by examining a surgical specimen oriented through a 3D-printed specific patient tongue with real-time Magnetic Resonance Imaging (MRI). We reported the preliminary results of a case series of 10 patients, prospectively enrolled, with oral tongue carcinoma who underwent surgery between February 2020 and April 2021. Two radiologists with 5 and 10 years of experience, respectively, in Head and Neck radiology in consensus evaluated specimen MRI and measured the distance between the tumor and the specimen surface. We performed intraoperative bedside FSA. To compare the performance of bedside FSA and MRI in predicting definitive margin status we computed the weighted sensitivity (SE), specificity (SP), accuracy (ACC), area under the ROC curve (AUC), F1-score, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). To express the concordance between FSA and ex-vivo MRI we reported the jaccard index.ResultsIntraoperative bedside FSA showed SE of 90%, SP of 100%, F1 of 95%, ACC of 0.9%, PPV of 100%, NPV (not a number), and jaccard of 90%, and ex-vivo MRI showed SE of 100%, SP of 100%, F1 of 100%, ACC of 100%, PPV of 100%, NPV of 100%, and jaccard of 100%. These results needed to be validated in a larger sample size of 21- 44 patients.ConclusionThe presented method allows a more accurate evaluation of surgical margin status, and the first clinical experiences underline the high potential of integrating FSA with ex-vivo MRI of the fresh surgical specimen.

A positive resection margin is one of the most significant risk factors for local breast cancer recurrence following breast-conserving surgery (BCS). Intraoperative specimen mammography (SMMG) is routinely used to evaluate the surgical margin at our institution. The aim of the present study was to assess the adequacy of SMMG for margin assessment. The patient cohort included 174 women who underwent BCS in 2006. The sensitivity and specificity of SMMG were assessed by comparing the margins assessed by histological and radiological methods. It was also examined whether the rate of positive histological margins was decreased by re-excision following SMMG evaluation. A total of 23 false-negatives and 6 false-positives were determined by SMMG. The sensitivity and specificity of SMMG margin assessment for patients with primary breast cancer were 20.6 and 94.6%, respectively. The positive predictive value was 50% and the negative predictive value was 82.2%. A subgroup analysis revealed that the sensitivity and specificity of SMMG in cases with ductal carcinoma in situ (DCIS) were higher compared with those in invasive ductal carcinoma. Furthermore, the positive histological margin rate was not affected by re-excision. Although the general usefulness of intraoperative SMMG was not proven, this procedure may be useful in specific cases, particularly those with DCIS and those diagnosed by stereotactic biopsy. A prospective study with exact criteria and a standard procedure is required.

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

Background:The challenge of breast-conserving surgery (BCS) is to remove the entire tumour with free margins and avoid secondary excision that may adversely affect the cosmetic outcome. Consequently, intraoperative evaluation of surgical margins is critical. The aims of this study were multiple. First, to analyse our methodology of intraoperative examination of the resection margins and to evaluate radiological and pathological methods in the assessment of the surgical margins. Second, to evaluate the factors associated with positive margins in our patient population.M&m:The data on the resection margin status of 290 patients who underwent BCS for invasive carcinoma or ductal carcinoma in situ (DCIS) between 2009 and 2016 were reviewed.Results:In the cohort of BCS with invasive carcinoma, the negative predictive value was 97.4% for intraoperative assessment by radiography and 81.8% for intraoperative assessment by pathology. The re-operation rate among cases without intraoperative assessment was 23.6% compared to 7.3% among cases with intraoperative assessment (P = .003). Margin status was significantly associated with tumour size, histological subtype (invasive lobular carcinoma), and multifocality. In the population of BCS with DCIS, margin status was significantly associated with preoperative localisation and intraoperative margin assessment (P = .03).Conclusion:There is no statistical difference between pathological and radiological intraoperative assessment. Tumour size, lobular subtype, and multifocality were found to be significantly associated with positive margins in cases with invasive carcinoma, whereas absence of intraoperative margin assessment was significantly associated with positive margins in cases with DCIS. Therefore, intraoperative margin assessment improves the likelihood of complete excision of the lesion.

To determine the effectiveness of specimen mammography in breast conserving surgery cases with respect to reduction in margin positivity rate, and to see whether the rate of secondary surgeries is decreased by intra-operative excision based on specimen mammography evaluation. The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data from January 2018 to December 2019 related to all female breast cancer patients who underwent mastectomy or breast conserving surgery with the involvement of specimen mammography. Sensitivity, specificity, positive predictive value and negative predictive value of specimen mammography were calculated. Data was analysed using SPSS 20. Of the 226 patients initially assessed, 65(28.7%) were excluded, and the final sample comprised 161(71.2%) women with mean age 46.71±10.47 years. The sensitivity, specificity, positive predictive value and negative predictive value of specimen mammography for the sample were 65.8%, 80.8%, 54% and 87.3%, respectively. Performing specimen mammography for intra-operative margin assessment in 12 patients was likely to spare one patient from re-excision. Intra-operative specimen mammography was found to be a reliable tool for assessing margin status.

Breast conserving surgery (BCS) is increasingly done for early breast cancers in many countries since it has been demonstrated by randomized trials that survival rates after BCS followed by adjuvant therapy are equivalent to those obtained after mastectomy. Frozen section analyses (FSA) is a technique used for intra-operative assessment of margin status in BCS. The aim of this study was to assess the concordance of margin status assessment by FSA and permanent sections and to assess correlation with local recurrence. A total of 162 patients underwent BCS for in situ or invasive carcinoma with FSA of margins during the year 2008 at our center. The inclusion criteria in this study were patients with intact tumor at the time of surgery. After application of the inclusion criteria, 60 patients could be included in this study. After frozen section, 20 patients had an initial negative margin. 40 subjects underwent additional excisions at the time of initial surgery because of close or positive margins. Of these 40 patients, in 32 patients a negative margin could be achieved with re-excisions. Pathological analyses of frozen section showed concordance to permanent sections in all cases. At a median follow-up of 40 months, there were no local recurrences. Intra-operative FSA allows resection of suspicious margins at the time of primary conservative surgery and results in low rates of local recurrence and second surgeries. There is good concordance between results of FSA and the final paraffin section in assessing margin status.

Breast carcinoma is the most frequently diagnosed malignancy in women of North America. The combination of breast conservation surgery and radiotherapy has become a standard of treatment for the majority of breast cancers. It is critical to obtain clear margins to minimize local recurrence. However, avoiding multiple re-excisions for margin clearance helps optimize cosmetic results in patients undergoing breast conservation surgery. Intra-operative touch preparation cytology (IOTPC) may decrease the need for multiple re-excisions and thereby improve cosmesis. The literature suggests that IOTPC can be useful in evaluation of margins. Klimberg et al. evaluated the touch preparation technique prospectively in 428 patients undergoing breast biopsy for undiagnosed breast masses. Margin evaluation was correct in 100% of the lesions and was used to re-excise the margins when touch prep results were positive. They reported a diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 100% for the touch prep technique. To the best of our knowledge, there has been no published data on the role of IOTPC for evaluation of margins in re-excision cases. This report describes our experience with IOTPC for margin assessment for re-excision partial mastectomy at Beth Israel Medical Center (BIMC). The purpose of this study is to determine whether IOTPC is reliable for evaluating margins in patients undergoing re-excision for involved or close margins. A prospective study of 30 patients, who have undergone re-excision partial mastectomy for involved or close margins after breast conservation surgery with the use of IOTPC for margin assessment at BIMC was performed. The re-excision lumpectomy specimens were oriented by the surgeon intra-operatively and were submitted fresh to pathology for cytologic assessment. The touch prep method consisted of touching the corresponding margin onto the glass slide. The principle of this technique is that if cancer cells are present they will stick to the slide, while fat cells will not. A slide was prepared for each re-excision specimen. Air-dried samples were stained immediately using the Diff-Quik method and examined under the microscope by a cytopathologist. Thirty patients underwent re-excision lumpectomy for involved or close margins with touch preparation cytology for assessment of 68 margins. Twenty-six patients had invasive ductal carcinoma and/or ductal carcinoma in situ, three patients had invasive lobular carcinoma and the remaining one patient had a combination of invasive lobular and ductal carcinoma. There was a correlation between touch prep cytology and final pathology in 56/68 margins, which accounts for 82.4% of the cases. Intra-operative touch preparation cytology for assessment of margins in patients undergoing re-excision lumpectomy for involved or close margins has a sensitivity of 75%, specificity of 82.8%, positive predictive value of 21.4%, and negative predictive value of 98.2%. This high negative predictive value and a single false negative margin are quite significant. Therefore, based on our experience, IOTPC can be a useful tool for intra-operative assessment of margins for patients undergoing re-excision partial mastectomy.

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.

Valor de la evaluación intraoperatoria del margen quirúrgico para el diagnóstico de margen afecto en cirugía conservadora del cáncer de mama

Intraoperative frozen section analysis is commonly used to evaluate marrow margins during extremity bone sarcoma resections, but its efficacy in the era of magnetic resonance imaging is debated. This study aimed to compare the accuracy of intraoperative frozen section assessment with final pathology, assess its correlation with gross intraoperative margin assessment, and evaluate its impact on surgical decision making. Consecutive patients undergoing extremity bone sarcoma resections from 2010 to 2022 at a single sarcoma center were included. Intraoperative frozen section and gross margin assessments were compared to final pathology using positive predictive values (PPV) and negative predictive values (NPV). Changes in surgical decisions due to positive intraoperative margins were recorded. Of 166 intraoperative frozen section marrow margins, four were indeterminant/positive, with two false positive/indeterminant findings and two false negatives compared to final pathology. Gross intraoperative assessment had no false positives and two false negatives. Frozen section analysis yielded a PPV of 50% (95% confidence interval [CI]: 16%-84%) and NPV of 98.8% (95% CI: 97%-100%), while gross assessment had a PPV of 100% (95% CI: 16%-100%) and NPV of 98.8% (95% CI: 97%-100%). Positive frozen section margins led to additional resections in three of four cases. Intraoperative frozen section analysis did not offer added clinical value beyond gross margin assessment in extremity bone sarcoma resections. It exhibited a low PPV and led to unnecessary additional resections. Gross intraoperative assessment proved adequate for margin evaluation, potentially saving time and resources.

Breast-conserving surgery (BCS) is established as a standard treatment option for women with early-stage invasive breast cancers. Margin status predicts local disease recurrence. Up to 59% of patients may undergo re-excision of their tumour cavity to establish clear margins. Intra-operative margin assessment may decrease re-excision rates. It is unclear if this procedure increases operative time. We compared intra-operative macroscopic assessment of margins, routine cavity shave margins and no formal intra-operative margin assessment to assess their impact on re-excision rates, residual disease burden and operative time. Over a 42month period, 188 patients from our retrospective breast cancer database were reviewed in our study. Of these, 68 had macroscopic margin assessment, 70 had cavity shave margins and 50 had no formal intra-operative assessment. Statistical analysis was performed as appropriate. Formal intra-operative margin assessment had a re-excision rate of 25%, compared with 34% for those without formal assessment. Formal assessment had a significantly reduced likelihood of having residual disease following the primary procedure (p=0.02). Close margins (<2mm) also predicted the presence of residual disease (p=0.01). There was no difference in operative duration between the groups. Directed intra-operative margin assessment reduces residual disease burden in BCS without increasing operative duration.

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.