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Can micro-computed tomography imaging improve interpretation of macroscopic margin assessment of specimen radiography in excised breast specimens?


1 Telethon Kids Institute, University of Western Australia, Perth Children's Hospital, Nedlands; Centre for Microscopy, Characterisation and Analysis, University of Western Australia, Crawley, Australia
2 Breast Centre, Department of Diagnostic and Interventional Radiology, Sir Charles Gairdner Hospital; University of WA School of Medicine; Breast Screen WA, Perth, Western Australia, Australia

Date of Submission05-Nov-2019
Date of Decision18-Jan-2020
Date of Acceptance22-Apr-2020
Date of Web Publication06-Oct-2020

Correspondence Address:
Anita G Bourke,
Breast Centre, Sir Charles Gairdner Hospital, Verdun St., Nedlands, Western Australia, 6009
Australia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_949_19

 > Abstract 


Introduction: Peri-operative macroscopic margin assessment with standard intraoperative specimen radiography (IOSR) results in improved re-excision rates in excised breast tissue specimens but is limited. This study sought to improve the intraoperative margin assessment on standard IOSR techniques by utilizing noninvasive X-ray micro-computed tomography (micro-CT) imaging of breast tissue specimens to compare margins in three-dimensional with two-dimensional IOSR.
Methods: Patients with impalpable breast carcinoma, or suspected breast carcinoma, who were eligible for breast-conserving surgery were recruited. Margins were assessed within each specimen using standard IOSR, micro-CT, and histology techniques.
Results: Six malignant and three benign lesions were included for the analysis in this study. Micro-CT identified the same positive margin as IOSR in 3 out of 6 malignancies. However, margin status identified by micro-CT was concordant with pathological assessment in only one specimen. In comparison, margin assessment by IOSR correctly correlated with pathological margin status in three malignant specimens.
Conclusion: The use of micro-CT imaging in this study did not improve margin assessment in impalpable breast specimens when compared to standard specimen radiography (SR) assessment. However, future improvements in sample preparation and CT image acquisition processes may enhance the potential of micro-CT as a valuable imaging tool for improving margin assessment.

Keywords: Breast, excision, margin, micro-computed tomography, radiograph, specimen



How to cite this URL:
Abel TN, Bourke AG. Can micro-computed tomography imaging improve interpretation of macroscopic margin assessment of specimen radiography in excised breast specimens?. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 26]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=297396




 > Introduction Top


The goal of breast-conserving surgery (BCS) is to completely remove a lesion with a satisfactory tumor free margin in a single surgery. Achieving microscopically clear margins is necessary to minimize the risk of local recurrence.[1] However, additional operative intervention is often required to achieve adequate resection margins. Worldwide, re-excision (RE) rates are reported between 10% and 70%.[2],[3],[4],[5]

Mammographic screening has resulted in the increasing detection of impalpable breast cancers requiring preoperative localization before BCS. The most commonly used preoperative localization technique is hook wire localization.[6] An audit of hook wire localization BCS demonstrated RE rates of 30%.[7]

The accuracy of conventional SR for intraoperative margin assessment of excised breast specimens is variable[8] and thought to be influenced by specimen orientation, limitations of two-dimensional (2D) imaging of a three-dimensional (3D) specimen, and a high rate of nonspecific findings. Alternative imaging techniques such as specimen tomosynthesis and real-time 3D ultrasound may enhance macroscopic margin assessments.[9],[10],[11]

Furthermore, emerging technologies such as optical coherence tomography have been investigated as alternative tools to facilitate the assessment of tumor margin microscopically.[12] 2D intraoperative SR (IOSR) of all lesions removed by wide local excision (WLE) is our current standard practice and is supplemented by specimen ultrasound if the lesion is only visible by ultrasound.

X-ray micro-computed tomography (micro-CT) is a novel tool to facilitate noninvasive 3D imaging of small breast tissue specimens, but limited studies have used this technique to evaluate excised breast tissue specimens and assess margins intraoperatively. Recent studies have demonstrated that micro-CT is beneficial in assessing breast cancer specimens and visualizing tumour location.[13] Other studies by the same group also demonstrated that micro-CT is useful in evaluating lumpectomy margin status intraoperatively and can define tumor dimensions.[14],[15]

In this study, we sought to improve on the intraoperative margin status reporting on standard IOSR techniques by evaluating the added information provided by 3D assessment by micro-CT and see if any lessons learned from 3D could be translated to 2D IOSR reporting.


 > Methods Top


Tissue collection

The study was approved by Sir Charles Gairdner Human Research Ethics committee. Prospective consent, which allowed additional micro-CT imaging of excised breast tissue, was obtained from participants undergoing BCS. Inclusion criteria were women aged over 40 years, with a hook-wire, image-guided localized impalpable histologically confirmed invasive or in situ breast carcinoma on core biopsy, who were eligible for BCS based on clinical and radiologic findings, or those with an impalpable histologically “indeterminate” benign or intraductal lesion including papilloma's, which were being excised as a diagnostic open biopsy, according to local hospital protocol. All excised breast specimens were identified, orientated, and pinned on to a styrofoam bed by the surgeon in theater, as demonstrated in [Figure 1].
Figure 1: Specimen preparation. Stylised representation of specimen micro-computed tomography to demonstrate pinning and orientation of excised breast specimens on a styrofoam bed. All specimens were prepared by the surgeon in theatre. (a) Styrofoam bedding example. (b) Pinning example and mark up of excised breast specimen. (c) Preparation of sample for transport from theatre

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Specimen radiograph

During the study, it was standard practice for all excised orientated and pinned breast specimens to be evaluated by standard departmental SR (GE Medical) in the Breast Clinic [Figure 2]a, [Figure 2]c and [Figure 2]e at Sir Charles Gairdner Hospital. The X-ray specimen images were reviewed immediately by a duty radiologist, and a verbal report documenting the closest margin was telephoned to the theater. The closest macroscopic margin was measured by taking the shortest distance between the macroscopic edge of a lesion and the edge of the specimen. If the margin was close, the surgeon took an appropriate cavity shave. The assumption is the anterior and posterior margins are completely excised as our surgeons excise a column of tissue from the skin to the chest wall, so the radial margins are assessed on 2-plane IOSR. Measurements were made in two projections, supero-inferior and mediolateral. A satisfactory macroscopic margin was defined as 10 mm or greater.
Figure 2: Representative radiograph and micro-computed tomography images of malignant breast specimens. (a, c and d) Representative specimen radiograph images. (b, d and f) Corresponding cross sectional micro-computed tomography images. (a and b) Shows malignant specimen 1 (M1), (c and d) show malignant specimen 2 (M2), (e and f) show malignant specimen 5 (M5)

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Micro-computed tomography

All study specimens were imaged by X-ray Micro-CT using thein vivo Skyscan1176 micro-CT system (Bruker, Belgium), which incorporates a 20–90 kV X-ray source. Specimens were imaged at 45 kV, using a 0.5 mm filter, with an incremental rotation step of 0.7 degrees, and a frame averaging of 2. The average time for imaging each specimen was <30 min [Figure 2]b, [Figure 2]d and [Figure 2]f.

All 2D cross-sections were reconstructed using Bruker's Nrecon program with an average processing time of 7 min. 3D images were visualized using DataViewer and CTVox. Reconstructed images were evaluated for radiographic signs of margin involvement, including clustered microcalcifications and nondecalcified lesions. Margin measurements were made using DataViewer A satisfactory radiological margin was defined as 10 mm or greater.

A separate review was then made comparing the margins on IOSR with micro-CT and the gold standard, histology. The macroscopic and microscopic pathological assessment was made by the pathologist on duty. A satisfactory macroscopic margin was defined as 10 mm or greater.


 > Results Top


Nine breast specimens from eight participants undergoing BCS were included in this study. All lesions were detected on mammogram screening [Table 1] and diagnosed by core biopsy preoperatively, which was followed by hook wire localization and excision. The mean patient age was 60 (range 48–74). Details of each specimen and margin assessment are summarized in [Table 1], [Table 2], [Table 3].
Table 1: Patient demographics and mammographic observations of malignant and benign lesions

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Table 2: Margin status of malignant lesions as assessed by intraoperative specimen radiography, micro-computed tomography and histology

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Table 3: Confirmation of excision of benign lesions as assessed by intraoperative specimen radiography, micro.computed tomography and histology

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micro-CT identified the same positive margin as IOSR in 2/6 malignancies [Table 1]. However, 2/6 Micro-CT assessments were inconclusive due to the presence of metal artifacts from the hook-wire in the micro-CT image. Micro-CT identified the involvement of the margin by tumor in one malignancy, which was called clear on radiography.

Margin status, identified by micro-CT, was concordant with pathological assessment in two specimens (case M2 and M4). Margin assessment by IOSR correctly correlated with pathological margin status in malignant specimens M3 (involved margins), M4 (involved margin) and M5 (clear margin). In one case (M4), an intra-operative shave cavity had clear margins, which meant a RE was not necessary. SR assessment identified one false-positive margin in a lobular carcinoma (M5) and one false-negative margin in lobular carcinoma in situ ( LCIS) (M2) and in one case, assessment was inconclusive (M1). Pathological analysis of the six malignancies confirmed one lesion was invasive ductal carcinoma, two invasive lobular carcinomas, two ductal carcinomas insitu, and one pleomorphic LCIS. Two patients had pathologically positive margins (M2 and M3), and the involved margins were re-excised. One patient underwent a further RE to obtain clear margins. Three of six malignant specimens had positive margins on IOSR. Margin involvement in one specimen was inconclusive.

Three lesions were confirmed excised and with benign histology [Table 3].


 > Discussion Top


Between 2006 and 2007, over 12,600 breast cancers were reported in Australia. Of these, fifty percent of cancers are impalpable at diagnosis.Two-thirds of all screen-detected invasive breast cancers are smaller than 15 mm and 54% are smaller than 10 mm.[16] At least 95% of all lesions should be correctly identified at the first excision.[16] Most cancers (74%) are treated with WLE. A local audit has revealed positive margins in 30% of these.[7] RE rates in literature are reported as between 10% and 70%.[5],[17]

The challenging and desired outcome of lumpectomy for BCS for nonpalpable breast cancer is the successful removal of the lesion with an adequate margin and a cosmetically acceptable result in one operation. Delays in adjuvant chemotherapy and/or radiotherapy, wound infection, reduced cosmesis, postoperative anxiety for the patient, and health-care costs[6] are all well-documented results of RE for positive margins. National Accreditation Standards recommends a specimen X-ray or ultrasound (Level 2 recommendation) to assess the macroscopic margins for small/impalpable breast cancers to ensure the lesion has been excised.[18] However, SR is reliable at determining whether the target lesion has been removed, the correlation of SR margin orientation and measurement with final histological measurement is far less reliable.[19]

We wished to improve patient outcomes by improving the assessment of breast specimen margins to reduce the RE rate, i.e., save the patient a second operation. Immediate reporting of the gross margins on the specimen radiograph either as in-theater or departmental per-operative technique with careful interpretation will likely increase the immediate cavity shave rate but reduce the need for a separate RE.

Few studies have utilized micro-CT to assess breast tumors and margin involvement per-operatively. Tang et al.[13] suggest IOSR is a potentially useful tool to confirm the excision of a lesion but not margin status, but micro-CT has the potential to do both. Fewer studies[15] have incorporated this technique to improve margin status reporting of small, impalpable breast tumors and indicate further studies are necessary. Unfortunately, the use of micro-CT in this study did not improve intraoperative margin reporting when compared to the standard IOSR technique. However, a major limitation of this study was the small sample size making it difficult to statically assess the advantages of micro-CT imaging in margin assessment. Furthermore, this study was also limited by image artifacts due to the presence of the hook-wire in the specimen. This made it difficult to determine and visualize both microcalcifications and noncalcified lesions. The usefulness of micro-CT in margin assessment may have been improved if the hook-wire could have been removed, and larger sample size was included for study. This technique could also be trialed with Iodine 125 seed procedures. In addition, a noted practical drawback of using micro-CT is the current time taken for image acquisition, reconstruction, and interpretation of images. On average, image acquisition and reconstruction took reporting on gross margin status is required per-operatively. However, further improvements in micro-CT technology and computer systems may allow more rapid image acquisition to facilitate real-time margin assessment. The fact that micro-CT images can be rotated in all directions and cross sections of internal portions of specimens can be visualized from any angle may have potential in future. Specimen tomosynthesis is currently under study at this institution.


 > Conclusion Top


There was no additional useful information gained using micro-CT to assess the margins in impalpable breast specimens, and there was no improvement in the reporting of margins when compared to standard SR.

Acknowledgements

Author TNA was affiliated with the Centre for Microscopy, Characterisation and Analysis at the University of Western Australia at the time of the study and is now currently affiliated with Telethon Kids Institute. The authors acknowledge the facilities, and the scientific and technical assistance of the National Imaging Facility at the Centre for Microscopy, Characterisation, and Analysis, The University of Western Australia, a facility funded by the University, State and Commonwealth Governments, but there was no financial input from any source to this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

 
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