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MarginProbe device is able to reduce re-excision rate of breast conserving surgery in invasive and pre-invasive breast cancer independent from any patient or tumor related factors

San Antonio Breast Cancer Symposium – December 9-13, 2014

Blohmer JU (1,2), Tanko J (2), Groß J (1,2), Völker R (1,2)

1) Chrité Gyn and Breast Dept; Sankt Gertrauden Hosp Gyn and Breast Dept

Abstract

Background: A positive margin status after breast conserving surgery (BCS) is one of the strongest predictors of local recurrence of intraductal and invasive carcinoma. As much as 20-50% of all patients with BCS need to undergo a second operation in order to receive a free margin. In this study we tested the clinical performance of MarginProbe (Dune Medical Devices), a novel device for intraoperative margin evaluation.

Methods: A prospective clinical trial was performed: The device was applied to 150 lumpectomy specimen from consecutive patients with BCS treated during the first three months in 2013. The re-excision rate was compared to the re-excision rate of a historical group of 156 patients treated with BCS during the first three months in 2012, without the application of the device. We analyzed whether Margin Probe is affected by morphology, grading, size of the tumor, breast density, age, body-mass-index or the use of wire-marker.

Results: Due to the application of Margin Probe the re-excision rate decreased significantly by 51% from 29.7% to 14.6%. In the subgroup of intraductal carcinoma (DCIS) the re-excision rate was reduced about two thirds from 66.7% to 23.1%. In the subgroup of lobular carcinomas the re-excision rate decreased from 37.0% to 19.0%. MarginProbe results are not affected by grading, tumor size, breast-density, age, body-mass-index or wire-marker application.

Conclusion: MarginProbe is an effective tool for detecting of positive margins during BCS and significantly decreases the re-excision rate. It is not limited to invasive carcinoma but also detects involved margins in DCIS as well as lobular carcinoma. It does not interfere with any of the factors we examined.

Background

The aim of breast conserving surgery is to achieve clear margins (R0-resection). In cases of non-palpable invasive cancer or DCIS the lesion has to be marked with wire or with radioguided occult lesion localization and intraoperatively examined. Methods of intraoperative evaluation are: touch prep cytology, frozen sectioning, gross examination (1-3). A new method is intraoperative ultrasound (IOUS). One prospective randomized study of IOUS for palpable breast cancer lesions showed a significant reduced re-excision rate (ROR) and resection volume compared with standard of care (SOC)(4). The same results were seen in a meta-analysis of IOUS for palpable and non-palpable breast cancer lesions (5). A new method is also MarginProbe (MP). In multiple studies with this technique a reduction of ROR were seen. In a prospective randomized study for nonpalpable invasive breast cancer and DCIS differences in ROR between MarginProbe group and SOC surgical method were evaluated (6). 664 patients from 21 clinics were included. The ROR was reduced by 57% (MP: 14.1%; control group: 29.9%; p<0.0001). There was a mild increased resection volume in MP-group. The German MP-study (7) included only patients (55) with pure DCIS of three clinics. The MP results were compared with historical data of breast conserving therapy for DCIS. Exsized specimen in both groups were intraoperatively examined with radiograms. The reduction of ROR were 56% (p=0.01) of MP-group compared with historical group.

Objective

The primary study endpoint is reduction ROR using MP. The secondary study endpoints are predictive factors for reduced ROR like tumor type, invasive cancer or DCIS, grading, tumor size, age of patient, breast density, body mass index (BMI), and palpable or no-palpable lesion.

Patients & Methods

The MarginProbe System is comprised of two distinct components; a hand-held probe and a console. The console includes a display, audio components and operation buttons. The probe is a detachable, sterile, single-use, single-patient component. It is connected to the console by cables and a vacuum tube, via a single connector. The system utilizes radiofrequency spectroscopy to characterize human tissue in real-time, measuring differences in dielectric properties between normal and malignant breast tissue (7).

From November 22th 2012 to June 11th 2013 all patients undergoing breast conserving surgery (BCS) in Berlin Sankt Gertrauden hospital with invasive breast cancer and pure DCIS were intraoperatively examined with MP, in addition to SOC (which included gross pathology examination). This prospective study were approved from local ethic committee. All patients gave their informed and written consent. The control group were patients with BCS and invasive and pre-invasive breast cancer treated from December 1st 2011 to March 15th 2012.

Blohmer Study 2 Tables

Results and Summary

The MP-group included 150 patients with invasive breast cancer and DCIS. 8 surgeons performed the BCS, 4 of them performed 84% of these BCS. The control group included 156 patients. Due to use of MP the ROR (related to patients) was significantly reduced (p=0.001) by 51% (29.7% vs. 14.6%). The number of ROR procedures was significantly reduced by 55% (33.7% vs. 15.3%). The ROR was significant reduced for the sub-group of invasive breast cancer, especially in NST (No special type). For the sub-groups of lobular invasive cancer and pure DCIS, with use of MP the ROR was reduced, but not significantly. The reduction of ROR with MP use was not significantly dependent on grading, breast density, age and BMI, or whether the breast cancer was palpable or not. The R0-rate (patients with clear margins) of the MP and control groups were 78% and 67.4%, respectively. An additional 1.8 ml (average) of breast tissue were removed in the MP group.

Blohmer Study 2 Figure 1

Discussion

According to published data and our now presented study it is possible to reduce ROR by 50% using the MarginProbe. We note that while the MarginProbe is approved by the respective regulatory authority in the USA and in Germany, it is not universally approved. There are other intraoperative methods for evaluating margin status, such as intraoperative ultrasound. Every clinic and health care system should evaluate whether the use of the MarginProbe fits their system.

About Dune Medical Devices

Dune Medical Devices was founded in 2002 by Dr. Dan Hashimshony, CEO, to realize the extraordinary medical potential of its proprietary tissue characterization technology. Offering surgeons and radiologists the real-time ability to identify cancerous tissues and react immediately, this technology holds the potential for a broad range of surgical and diagnostic applications. Dune Medical Devices is a privately held company with offices in the U.S. and Israel.

Interested in learning more about the Margin Probe system, or putting it to use in your facilities? Contact us at info@dunemedical.com.

References

1. www.ago-online.de

2. S3-Leitlinie zur Diagnostik, Therapie und Nachsorge des Mammakarzinoms, herausgegeben von der Deutschen Krebsgesellschaft 2012

3. Untch U, Gerber B, Harbeck N, Jackisch C, Marschner N, Möbus V, von Minckwitz G, Loibl S. 13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence, Controversies, Consensus – Opinion of a German Teamof Experts (Zurich 2013). Breast Care 2013;8:221– 229

4. Krekel NM, Haloua MH, Lopes Cardozo AM, de Wit RH, Bosch AM, de Widt-Levert LM, Muller S, van der Veen H, Bergers E, de Lange de Klerk ES, Meijer S, van den Tol MP. Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial. Lancet Oncol. 2013;14:48-54.

5. Pan H, Wu N, Ding H, Ding Q, Dai J, Ling L, Chen L, Zha X, Liu X, Zhou W, Wang S. Intraoperative Ultrasound Guidance Is Associated with Clear Lumpectomy Margins for Breast Cancer: A Systematic Review and Meta-Analysis. PLoS ONE 2013;8(9): e74028. doi:10.1371/journal.pone.0074028

6. Rivera RJ, Holmes DR, Tafra L. Analysis of the Impact of Intraoperative Margin Assessment with Adjunctive Use of MarginProbe versus Standard of Care on Tissue Volume Removed.. Int J Surg Oncol. 2012 Dec 26 (EPub)

7. Thill M, Dittmer C, Baumann K, Friedrichs K, Blohmer JU. MarginProbe – Final results of the German postmarket study in breast conserving surgery of ductal carcinoma in situ. The Breast 2014;23: 94-96