Methods Of Margin Assessment Research Articles

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.

Cost Analysis of a Surgical Consensus Guideline in Breast-Conserving Surgery

The Society of Surgical Oncology and American Society of Radiation Oncology consensus statement was the first professional guideline in breast oncology to declare "no ink on tumor" as a negative margin in patients with stages I/II breast cancer undergoing breast-conservation therapy. We sought to analyze the financial impact of this guideline at our institution using a historic cohort. We identified women undergoing re-excision after breast-conserving surgery for invasive breast cancer from 2010 through 2013 using a prospectively maintained institutional database. Clinical and billing data were extracted from the medical record and from administrative resources using CPT codes. Descriptive statistics were used in data analysis. Of 254 women in the study population, 238 (93.7%) had stage I/II disease and 182 (71.7%) had invasive disease with ductal carcinoma in situ. A subcohort of 83 patients (32.7%) who underwent breast-conservation therapy for stage I/II disease without neoadjuvant chemotherapy had negative margins after the index procedure, per the Society of Surgical Oncology and American Society of Radiation Oncology guideline. The majority had invasive ductal carcinoma (n= 70 [84.3%]) and had invasive disease (n= 45 [54.2%]), and/or ductal carcinoma in situ (n= 49 [59.0%]) within 1 mm of the specimen margin. Seventy-nine patients underwent 1 re-excision and 4 patients underwent 2 re-excisions, accounting for 81 hours of operative time. Considering facility fees and primary surgeon billing alone, the overall estimated cost reduction would have been $195,919, or $2,360 per affected patient, under the guideline recommendations. Implementation of the Society of Surgical Oncology and American Society of Radiation Oncology consensus guideline holds great potential to optimize resource use. Application of the guideline to a retrospective cohort at our institution would have decreased the overall re-excision rate by 5.6% and reduced costs by nearly $200,000. Additional analysis of patient outcomes and margin assessment methods is needed to define the long-term impact on surgical practice.

Volumetric x-ray coherent scatter imaging of cancer in resected breast tissue: a Monte Carlo study using virtual anthropomorphic phantoms

Breast cancer patients undergoing surgery often choose to have a breast conserving surgery (BCS) instead of mastectomy for removal of only the breast tumor. If post-surgical analysis such as histological assessment of the resected tumor reveals insufficient healthy tissue margins around the cancerous tumor, the patient must undergo another surgery to remove the missed tumor tissue. Such re-excisions are reported to occur in 20%–70% of BCS patients. A real-time surgical margin assessment technique that is fast and consistently accurate could greatly reduce the number of re-excisions performed in BCS. We describe here a tumor margin assessment method based on x-ray coherent scatter computed tomography (CSCT) imaging and demonstrate its utility in surgical margin assessment using Monte Carlo simulations. A CSCT system was simulated in Geant4 and used to simulate two virtual anthropomorphic CSCT scans of phantoms resembling surgically resected tissue. The resulting images were volume-rendered and found to distinguish cancerous tumors embedded in complex distributions of adipose and fibroglandular breast tissue (as is expected in the breast). The images exhibited sufficient spatial and spectral (i.e. momentum transfer) resolution to classify the tissue in any given voxel as healthy or cancerous. ROC analysis of the classification accuracy revealed an area under the curve of up to 0.97. These results indicate that coherent scatter imaging is promising as a possible fast and accurate surgical margin assessment technique.

Fat/water ratios measured with diffuse reflectance spectroscopy to detect breast tumor boundaries.

Recognition of the tumor during breast-conserving surgery (BCS) can be very difficult and currently a robust method of margin assessment for the surgical setting is not available. As a result, tumor-positive margins, which require additional treatment, are not found until histopathologic evaluation. With diffuse reflectance spectroscopy (DRS), tissue can be characterized during surgery based on optical parameters that are related to the tissue morphology and composition. Here we investigate which optical parameters are able to detect tumor in an area with a mixture of benign and tumor tissue and hence which parameters are most suitable for intra-operative margin assessment. DRS spectra (400-1600 nm) were obtained from 16 ex vivo lumpectomy specimens from benign, tumor border, and tumor tissue. One mastectomy specimen was used with a custom-made grid for validation purposes. The optical parameter related to the absorption of fat and water (F/W-ratio) in the extended near-infrared wavelength region (~1000-1600 nm) provided the best discrimination between benign and tumor sites resulting in a sensitivity and specificity of 100 % (excluding the border sites). Per patient, the scaled F/W-ratio gradually decreased from grossly benign tissue towards the tumor in 87.5 % of the specimens. In one test case, based on a predefined F/W-ratio for boundary tissue of 0.58, DRS produced a surgical resection plane that nearly overlapped with a 2-mm rim of benign tissue, 2 mm being the most widely accepted definition of a negative margin. The F/W-ratio provided excellent discrimination between sites clearly inside or outside the tumor and was able to detect the border of the tumor in one test case. This work shows the potential for DRS to guide the surgeon during BCS.

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.

Impact of Margin Assessment Method on Positive Margin Rate and Total Volume Excised

For breast-conserving surgery, the method of margin assessment that most frequently achieves negative margins without increasing the volume of tissue excised is uncertain. We examined our institutional experience with three different margin assessment methods used by six experienced breast surgeons. Patients undergoing breast-conserving surgery for invasive carcinoma during July to December of a representative year during which each method was performed (perpendicular, 2003; tangential, 2004; cavity shave, 2011) were included. The effect of margin method on the positive margin rate at first excision and the total volume excised to achieve negative margins were evaluated by multivariable analysis, by surgeon, and by tumor size and presence of extensive intraductal component (EIC). A total of 555 patients were identified, as follows: perpendicular, 140; tangential, 124; and cavity shave, 291. The tangential method had a higher rate of positive margins at first excision than the perpendicular and cavity-shave methods (49, 15, 11 %, respectively; p < 0.0001). Median volumes to achieve negative margins were similar (55 ml perpendicular; 64 ml tangential; 62 ml cavity shave; p = 0.24). Four of six surgeons had the lowest rate of positive margins with the cavity-shave method, which was significant when compared to the tangential method (p < 0.0001) but not the perpendicular method (p = 0.37). The volume excised by the three methods varied by surgeon (p < 0.0001). The perpendicular method was optimal for T1 tumors without EIC; the cavity-shave method tended to be superior for T2-T3 tumors and/or EIC. Although the cavity-shave method may decrease the rates of positive margins, its effect on volume is variable among surgeons and may result in an increase in the total volume excised for some surgeons and for small tumors without EIC.

Therapeutic Mammaplasty for Breast Cancer: Oncological and Aesthetic Outcomes

Therapeutic mammaplasty (TM) for breast cancer is a widely practiced oncoplastic technique. Patient selection criteria and method of margin assessment are not clearly established. The aim of our review was to analyse oncological and aesthetic outcomes over a 7 year period. We conducted a retrospective review of 251 breast cancer patients who underwent TM from 2002 to 2009 at the Netcare Breast Care Centre, Johannesburg. Primary chemotherapy was used to downsize large tumours. Intraoperative margin assessment was performed. Statistical analysis was performed using Kaplan-Meier estimates. Cosmetic outcomes were assessed by an independent review panel using photographic material. Mean tumour size was 15.4 mm. Mean resection weight was 237 g. Sixty-four (25.5 %) patients received primary chemotherapy. Mean margin taken was 15 mm. The back-to-theatre rate was 2 % (5 cases). A total of 222 patients underwent bilateral procedures. Contralateral occult disease was identified in six cases (2.4 %). The early (<2 months) complication rate was 3.2 %. Late complications were related to adjuvant radiotherapy (20.7 %). Mean follow-up was 50 months. The recurrence rate was 4 %. Five of six patients with locoregional recurrence had DCIS at initial surgery. The mortality rate was 3.2 %. The overall survival rate was 96.4 % and the metastasis-free survival rate was 94.6 %. Acceptable aesthetic results were achieved in 96 % of the patients. Primary chemotherapy allowed for TM in patients with large tumours. Intraoperative margin assessment decreased reoperation rate. Contralateral matching procedures resulted in histological detection of occult disease. TM is an oncologically appropriate and cosmetically favourable technique.

Assessing Breast Cancer Margins Ex Vivo Using Aqueous Quantum-Dot-Molecular Probes

Positive margins have been a critical issue that hinders the success of breast- conserving surgery. The incidence of positive margins is estimated to range from 20% to as high as 60%. Currently, there is no effective intraoperative method for margin assessment. It would be desirable if there is a rapid and reliable breast cancer margin assessment tool in the operating room so that further surgery can be continued if necessary to reduce re-excision rate. In this study, we seek to develop a sensitive and specific molecular probe to help surgeons assess if the surgical margin is clean. The molecular probe consists of the unique aqueous quantum dots developed in our laboratory conjugated with antibodies specific to breast cancer markers such as Tn-antigen. Excised tumors from tumor-bearing nude mice were used to demonstrate the method. AQD-Tn mAb probe proved to be sensitive and specific to identify cancer area quantitatively without being affected by the heterogeneity of the tissue. The integrity of the surgical specimen was not affected by the AQD treatment. Furthermore, AQD-Tn mAb method could determine margin status within 30 minutes of tumor excision, indicating its potential as an accurate intraoperative margin assessment method.

Association of margin assessment method with reexcision rates in breast-conserving surgery (BCS).

e11018 Background: The need for reexcision after BCS is common, reported to be > 50% in some series. We examined reexcision rates using 3 different methods of margin assessment (METHODs) at our institution from 2003-2008. Methods: The study population consisted of all patients completing BCS and sentinel node biopsy after needle biopsy diagnosis of breast cancer from Jul-Dec 2003, 2004, and 2008. These 3 time periods corresponded to 3 METHODs: perpendicular (P) (pathologist-evaluated perpendicular margins in serial sections of the specimen, 2003), tangential shaved (T) (pathologist shaved margins from the specimen, 2004), and cavity shaved (C) (surgeon shaved margins from the cavity, 2008). The need for > 1 excision and the volume of tissue excised were examined for each METHOD. Kruskal-Wallis and Chi-squared tests were used for statistical analysis. Results: For each METHOD, the number of cases was as follows: P =174, T = 160, and C = 299. Overall, positive margin rates were higher for T than P or C (p < 0.0001) resulting in rates of > 1 excision in 35% (T), 28% (P) and 24% (C) (p = 0.05). Cases with extensive intraductal component (EIC) required > 1 excision in 38%, vs. 27% of non-EIC cases (p = 0.01). Among women with EIC, the proportion needing > 1 excision rose to 54% (T), 29% (P), and 36% (C) while cases without EIC underwent > 1 excision in 30% (T), 28% (P), and 24% (C). The initial excision volume was significantly lower for P than for the other methods (mean, 63 cc [P] vs. 78 cc [C], 70 cc [T], p = 0.003). Among surgeons, there was variability in initial volume excised (p < 0.0001) and need for > 1 excision (p = 0.02). However, for 6 of the 9 surgeons, the C METHOD resulted in the lowest reexcision rate. Conclusions: METHOD has a significant impact on reexcision rates; risks and benefits of each method must be weighed. T results in higher margin positivity and reexcision rates than P and C, while P has lower excision volumes. Although P and C have similar reexcision rates, C has an advantage in that it allows the surgeon to more accurately define margins of resection, thereby directing reexcision more precisely. Lower volume of excision in P, however, may translate to better cosmesis. No significant financial relationships to disclose.

Is the difference in reexcision rate of various margin assessment methods due solely to difference in volume excised?

593 Background: The inability to achieve clear margins in a single operation continues to plague breast surgeons, resulting in reexcision rates of up to 70%. We explored 3 different methods of margin assessment (METHODs) and found that the cavity shave technique (C) resulted in significantly lower reexcision rates, but larger volumes of excision. Here, we assessed whether the lower reexcision rate was due solely to the larger volume excised. Methods: Our study population consisted of consecutive patients undergoing breast conservation with sentinel node biopsy after a needle biopsy diagnosis of invasive carcinoma or DCIS from July-December of 2003, 2004, and 2008. These 3 time periods corresponded to 3 METHODs: perpendicular (P) (pathologist evaluated perpendicular margins in serial sections of the specimen, 2003), tangential shaved (T) (pathologist shaved margins from the specimen, 2004), and cavity shaved (C) (surgeon shaved margins from the cavity, 2008). Volume of tissue excised at initial excision was the sum of the volume of lumpectomy (calculated by πABC/6, where A, B, C are 3 dimensions of specimen) and additional margins taken (calculated by πABH/4, where A, B are diameters, H is thickness). Using univariate and multivariate logistic regression, we modeled the outcome of >1 excision versus 1 excision with METHOD and ln(volume) as predictors. Results: See Table. On univariate logistic regression, both METHOD (OR 1.7 for T vs. C, p=0.03) and volume (OR=0.8 for ln[volume], p=0.02) were statistically significantly associated with need for reexcision. When adjusted for volume, METHOD remained significant (OR 1.6 for T vs. C, p=0.02). Conclusions: Our study showed that while C is associated with a larger volume of excision, the lower reexcision rate seen is not due solely to the larger volumes excised. These data suggest that other factors resulting in reexcision, such as artifactual ink at or near tumor, are less likely with C technique due to the separate margins resected. Hazard ratios with 95% confidence intervals Perpendicular (P) Tangential shave (T) Cavity shave (C) P value Number of breasts 174 160 299 Reexcision rate 28% 35% 24% 0.05* Mean volume 63 cm3 70 cm3 78 cm3 0.003† * Chi-squared test. † ANOVA model using ln(volume). No significant financial relationships to disclose.

Methods of Margin Assessment in Breast Conserving Surgery

Methods of Margin Assessment in Breast Conserving Surgery

Perpendicular Inked Versus Tangential Shaved Margins in Breast-Conserving Surgery: Does the Method Matter?

In breast-conserving surgery (BCS), the method of margin assessment and the definition of a negative margin vary widely. The purpose of this study was to compare the incidence of positive margins and rates of reexcision between two methods of margin assessment at a single institution. In July 2004, our protocol for margin evaluation changed from perpendicular inked margins (Group A, n=263) to tangential shaved margins (Group B, n=261). In Group A, margins were classified as positive, close, and negative. Margins designated as "close" were further defined as: < or = 1 mm, < or = 2 mm, and < or =3 mm. In Group B, shaved margins (by definition 2 to 3 mm) were reported as positive or negative. The rate of reported "positive" margins was significantly higher in Group B: 127 of 261 (49%) versus 42 of 263 (16%), p < 0.001. But when patients with "positive, close, or both" kinds of margins were combined in Group A, there was no significant difference between the two techniques. Although the shaved margin was 2- to 3-mm thick, the rate of reexcision in Group B was significantly higher when compared with that in patients with "positive, close, or both" < or =3 mm margins in Group A (75% versus 52%, p < 0.001). The likelihood of finding residual disease remained the same (27% versus 32%, p=NS). The tangential shaved-margin technique results in a higher proportion of reported positive margins and limits the ability of the surgeon to discriminate among patients with close margins, resulting in a higher rate of reexcision. The fact that many, but not all, patients with positive or close margins in both groups underwent reexcision emphasizes the role of surgical judgment in this setting. Longer followup is required to determine equivalency in rates of local recurrence between these two methods of margin assessment.

Influence of breast cancer margin assessment method on the rates of positive margins and residual carcinoma

Background We hypothesized that the method of breast cancer margin assessment may be associated with different rates of positive margins and residual carcinoma. Methods A total of 178 breast cancer specimens were divided into 2 groups (A and B) based on the margin assessment method used. Rates of positive margins, re-excision, and residual carcinoma at re-excision were compared and analyzed statistically. Results At least 1 margin was positive in 64.7% in group A and in 65.2% in group B. At directed re-excision 54% in group A and 51% in group B had residual carcinoma. The lateral margin was positive in 44% in group A compared with 26% in group B ( P = .06). The posterior margin was positive in 19% in group A and in 51% in group B ( P = .001). Conclusions Two different breast cancer specimen margin assessment methods had comparable rates of positive margins and residual carcinoma at re-excision. Different patterns of specific margin positivity suggest that the method of margin assessment may alter results.

The relationship between shaved margin and inked margin status in breast excision specimens

The presence of tumor at the inked margins (IMs) of breast specimens is associated with an increased risk of local recurrence after breast-conserving therapy for invasive breast carcinoma and ductal carcinoma in situ (DCIS). Given the importance of margin status, some have advocated the use of shaved margins (SMs) as a means of conducting a more complete examination of the specimen margins than could be done with sections taken perpendicular to the IMs. However, it is not known whether these two methods of margin assessment provide comparable information. To address this issue, the authors studied 22 consecutive breast reexcision specimens (10 DCIS, 6 infiltrating ductal carcinomas, and 6 infiltrating lobular carcinomas) in which the specimen surfaces were inked, the margins were shaved, and tumor was present in at least one of the SM sections. A total of 199 SMs were examined. The SMs were originally embedded in a way that permitted histologic sections to be cut opposite the inked surface. Sections of SM stained with hematoxylin and eosin (H & E) were reviewed and scored for the presence and extent (number of low-power fields) of cancer. The remaining tissue from the SM was then removed from the blocks, cut perpendicular to the IM, and reembedded to permit visualization of tumor in relation to the IM. Sections were then cut from two different levels of each reembedded block and stained with H & E. An SM was considered positive if tumor was present anywhere on the section. An IM was considered positive when tumor extended to the inked surface. Although all 22 excisions had at least 1 positive SM, tumor was present at an IM in only 12 specimens (55%). Among 69 positive SMs, the corresponding IM was positive in only 42 (61%). The likelihood of a positive IM increased with the number of low-power fields of involvement by invasive carcinoma or DCIS on the SM, as follows: 19% with 1 low power-field, 67% with 2 low-power fields, and 97% with > or = 3 low-power fields (all P < 0.02). When the SM was negative, the corresponding IM was negative in 98% of cases. Many patients with positive SMs do not have positive IMs. A positive SM more reliably predicts a positive IM when tumor involves > or = 3 low-power fields of the SM. The authors conclude that the clinical implications of a positive SM may not be the same as those of a positive IM. Clinical outcome studies are needed to define further the implications of positive SMs. [See editorial counterpoint on pages 1453-8 and reply to counterpoint on pages 1459-60, this issue.]