Time Of Lumpectomy Research Articles

Targeted Intraoperative Radiotherapy (TARGIT-IORT) for Early-Stage Invasive Breast Cancer: A Single Institution Experience.

Purpose/ObjectiveWe present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines.Materials/MethodsWe identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient’s ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time.Results237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m2 were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 – 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%.ConclusionThere is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.

Abstract P3-19-12: Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial

Abstract Purpose: To investigate the association between ET noncompliance and ipsilateral breast tumor recurrence (IBTR) in the ExBRT trial (“A Safety and Efficacy Study of Intra-Operative Radiation Therapy [IORT] Using the Xoft® Axxent® Electronic Brachytherapy [eBx®] System at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer”). Methods: The IRB-approved single arm prospective nonrandomized multi-institutional ExBRT trial was designed to determine the efficacy and outcome of a single 20 Gy fraction of IORT delivered at the time of lumpectomy for early-stage breast cancer. The trial included women age ≥ 40 years with invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS) of all molecular subtypes documented by pre-operative biopsy which were ≤ 30 mm by clinical and radiographic evaluation. Tumors with pre-operative lymphovascular invasion and intra-operative positive lymph nodes and/or margins were excluded. ET was defined as treatment with tamoxifen, anastrozole, letrozole, and/or exemestane. Pts were classified as “Compliant with ET” if they completed a 60-month ET course or were compliant with ongoing ET. Pts were defined as “Discontinued ET” if they stopped ET prior to completing a 60-month ET course. Pts were classified as “Declined ET” if they did not initiate recommended ET. Data, collected at enrollment and at 1, 6, 12, 18 and 24 months, then yearly, included demographics, histopathology, estrogen receptor positivity (ER+), progesterone receptor positivity (PR+), adjuvant therapy, IBTR, and survival. The primary endpoint was IBTR. Preliminary results evaluating the impact of ET noncompliance on pts who successfully completed treatment with a single 20 Gy fraction of IORT per protocol are presented. Results: Between May 2012 - July 2018, 1105 pts (mean age 64 years) with pre-operative biopsy-proven IDC or DCIS successfully completed a single fraction of IORT treatment per protocol. Mean follow-up was 4.0 years (range 2-8 years). One-hundred fifteen (10%) pts, who were either ER negative or had an unknown ER status, are not included in this analysis. Pt cohorts and tumor characteristics are presented in Table 1. There were 39 (3.93%) IBTR in the ER+ subset at mean follow-up of 4 years. IBTR in the “Compliant with ET” group was 2.53%. Although the percentages were greater in the “Discontinued ET” (5.68%) and “Declined ET” (7.10%) cohorts, this did not reach statistical significance (Chi square test, p-value = 0.147). Conclusion: IORT allows pts to conveniently receive both their surgery and electronic brachytherapy radiation treatment in one setting. Early-stage ER+ breast cancer pts compliant with a subsequent course of ET in this study experienced a lower IBTR rate, improving the collective outcome of their multidisciplinary treatment. These preliminary ExBRT trial results demonstrate that IBTR rates are improved with ET compliance. Although this has not reached statistical significance in this trial, it may partially explain the slight differences in IBTR rates noted in comparison with similar electronic brachytherapy early-stage breast cancer studies. Table 1.IORT pt cohorts and tumor characteristicsCompliant with ETDiscontinued ETDeclined ETNNNER +631176183PR +597170162Mean age (years)65.766.366.7Postmenopausal580162161Mean tumor size (mm)11.110.712.7Tumor HistologyIDC524136120grade I2116055grade II2535955grade III54159Unknown grade621DCIS933756Low grade2099Intermediate grade421925High grade30922Unknown grade100Infiltrating lobular ca505Other932Chemotherapy given4286Ethnicity/RaceCaucasian498143151African American351013Hispanic46188Asian/Pacific Islander2812Native American211Other2238Recurrences16 (2.53%)10 (5.68%)13 (7.10%) Citation Format: Barbara Schwartzberg, AMNisar Syed, Robert Cohen, William Dooley, Maen Farha, Veronica Jones, Wesley Hodge. Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial [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 P3-19-12.

Long-Term Adherence to Adjuvant Endocrine Therapy Following Various Radiotherapy Modalities in Hormone Receptor Positive Breast Cancer

Adjuvant endocrine therapy (AET) is standard of care following breast-conserving surgery (BCS) for hormone receptor (HR) positive breast cancer. We compared the rates of long-term AET adherence after various radiation therapy (RT) modalities among patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer treated with BCS.Medical records from patients with stage 0 or stage 1, ER and/or PR positive breast cancer that received adjuvant RT between 2013 and 2015 at a single institution were retrospectively reviewed. We excluded patients with prior breast cancer or ductal carcinoma in situ (DCIS), HR-negative disease, primary tumors > 3cm, involved nodes, and those for whom AET was contraindicated. All patients received BCS followed by adjuvant RT via one of the following modalities: whole breast radiotherapy (WBI), accelerated partial breast irradiation (APBI) with either external beam radiation therapy (EBRT) or fractionated intracavitary high dose rate (HDR) brachytherapy, or single fraction HDR-brachytherapy intraoperative-radiation therapy (IORT) delivered at the time of lumpectomy, on a clinical trial (Precision Breast IORT). Only patients from the completed phase of the protocol were included. All patients were evaluated for up to five years of adherence to AET. Patient and treatment factors were evaluated via a Cox Regression analysis with backward selection of variables based upon P < 0.10 on univariate analysis (UVA) for inclusion in the final model. The Kaplan Meier method was used to model and further evaluate rates of AET adherence based on RT modality and histology as well as among the entire cohort.Ninety-seven patients were eligible for analysis. Thirty patients were treated with WBI, 41 with APBI, and 26 with IORT on clinical trial with a median follow up of 64.2, 72.0, and 58.6 months, respectively. Follow up schedule and evaluation of AET adherence was similar between all groups. For the entire cohort, AET adherence was approximately 67% at 2 years and 58% at 5 years. Among patients in the IORT clinical trial, adherence to AET was 53% at 2 years and 41% at 5 years. In the Cox regression model, histology (DCIS) and RT modality (IORT) were associated with decreased AET adherence at 5 years, with odds ratio (OR) 1.974 (CI: 1.018-3.828, P = 0.044) and OR 2.177 (CI: 1.132-4.186, P = 0.02), respectively.For early stage, HR positive breast cancer, the rate of AET adherence was approximately 58% at 5 years, consistent with prior reports. DCIS histology and receipt of IORT on clinical trial were associated with lower rates of adherence to AET at 5 years. Our findings suggest a potential need for further research aimed at addressing adherence to AET. Additionally, examination of the efficacy of more convenient RT interventions such as APBI and IORT in patients who do not receive AET is warranted.

Comparison of Tumor Bed Delineation Using a Novel Radiopaque Filament Marker vs. Surgical Clips for Targeting Breast Cancer Radiotherapy

<h3>Purpose/Objective(s)</h3> The accuracy of tumor bed (TB) delineation is essential for targeting boost dose or partial breast irradiation. Surgical clip markers (CM) are standardly used. However, despite using CM, multiple studies have shown high interobserver variability in TB delineation. We hypothesize that a radiopaque filament marker (FM) woven along the TB at the time of lumpectomy will improve accuracy of TB delineation. <h3>Materials/Methods</h3> An FDA-approved radiopaque filament was intraoperatively used to outline the tumor bed of patients undergoing lumpectomy. Between January 2020 and September 2020, 10 consecutive patients with the FM and 10 consecutive patients with the standard CM were identified for comparison. Five "experts," defined as board-certified radiation oncologists specializing in breast cancer, independently contoured all 20 tumor beds. Dice coefficients were then calculated for each patient by comparing the intersection and aggregate of each expert's contours with that of the other experts individually. An intersection and aggregate of the contours of all 5 experts was also analyzed for each patient. Dice coefficient of 1 represents perfect contour agreement, and 0 represents no agreement. Two-tailed paired samples t-tests were performed to compare dice coefficients between FM and CM cohorts. Furthermore, the center of mass (COM) coordinates were calculated to analyze the distance of the COM of each expert's contour to that of the aggregate of the other experts' contours for each patient. Two-tailed unpaired samples t-tests were performed to compare COM distances between FM and CM cohorts. <h3>Results</h3> For FM, mean dice coefficient and standard deviation for each expert was: 0.61 ± 0.09, 0.60 ± 0.10, 0.60 ± 0.10, 0.60 ± 0.09, and 0.55 ± 0.11, respectively. By comparison, for CM, mean dice coefficient and standard deviation for each expert was: 0.48 ± 0.22, 0.42 ± 0.25, 0.47 ± 0.21, 0.47 ± 0.22, and 0.40 ± 0.22, respectively. Thus, TB delineation agreement was significantly improved with FM (<i>P</i> = 0.0013, <i>P</i> = 0.0001, <i>P</i> = 0.0013, <i>P</i> = 0.0006, and <i>P</i> = 0.0008, respectively). Furthermore, the COM distance of each expert's contour to that of the aggregate of all experts' contours was significantly reduced (<i>P</i> < 0.001) from a mean of 0.96 cm ± 0.89 cm for CM to 0.25 cm ± 0.19 cm for FM. <h3>Conclusion</h3> Radiopaque filament resulted in significantly improved interobserver variability in tumor bed delineation compared with standard surgical clips. This difference was clinically meaningful with a reduction in mean COM contour disagreement from almost 1cm to 2.5mm, and suggests marked superiority of the radiopaque filament in targeting boost dose and/or partial breast irradiation.

Intraoperative Radiotherapy with Balloon-Based Electronic Brachytherapy System-A Systematic Review and First Bulgarian Experience in Breast Cancer Patients.

(1) Background: We aimed to analyze currently available studies with intraoperative radiotherapy (IORT) as a choice of treatment where the Xoft Axxent® electronic brachytherapy (eBx) system was used as a single-dose irradiation and an exclusive radiotherapy approach at the time of surgery in patients with early breast cancer (EBC). We also compared the results of the systematic review to the Bulgarian experience. (2) Methods and Materials: We performed a systematic review of the studies published before February 2021, which investigate the application of a single-fraction 20 Gy radiation treatment, delivered at the time of lumpectomy in EBC patients with the Xoft Axxent® eBx System. A systematic search in PubMed, Scopus, and ScienceDirect was performed. The results are reported following the PRISMA guidelines. The criteria on patients’ selection for IORT (the additional need for EBRT), cosmetic outcomes, and recurrence rate from the eligible studies are compared to the treatment results in Bulgarian patients. (3) Results: We searched through 1032 results to find 17 eligible studies. There are no published outcomes from randomized trials. When reported, the cosmetic outcomes in most of the studies are defined as excellent. The observed recurrence rate is low (1–5.8%). Still, the number of patients additionally referred to postoperative external breast radiotherapy (EBRT) is up to 31%. Amongst the 20 patients treated in Bulgaria, the cosmetic outcomes are also evaluated as excellent, five of which (25%) are referred for EBRT. Within median follow-up of 39 months, there was one local and one distal recurrence. (4) Conclusions: Current evidence demonstrates the Xoft Axxent® eBx system as a safe and feasible technique for IORT delivery in EBC patients. There are no randomized controlled trials conducted at this time point to prove its long-term effectiveness. Better patient selection and a reimbursement strategy have to be proposed to extend the application of this technique in Bulgaria.

Maintaining Contour with a Three-dimensional Interstitial Tissue Marker in 134 Lumpectomies.

Background:Breast-conserving surgery (BCS) is meant to preserve the natural appearance of the breast; however, tissue volume deficits cannot always be compensated by soft tissue mobilization. A three-dimensional (3D) interstitial tissue marker (BioZorb) was designed to delineate the lumpectomy cavity for targeting boost irradiation, but an unexpected secondary benefit may be in guiding wound contraction and restoring contour to the lumpectomy bed. We analyze tissue volume excised at the time of lumpectomy as a function of device size selected.Methods:In total, 134 consecutive lumpectomy patients implanted with BioZorb between May 2015 and February 2020 were retrospectively analyzed for tissue volume excised, device size used, location, and re-operation rates, including explantation of the device.Results:An estimated 113 patients underwent device implantation at initial lumpectomy, and 21 at margin re-excision. Twenty-seven patients underwent re-excision, while 14 elected mastectomy for positive margins following insertion; 22 had the same device reimplanted. Mean lumpectomy volume was 79.0 cm3 (range 10.3–275.8 cm3) during the first implant procedure. Large-volume lumpectomies, averaging 136.5 cm3, were associated with selection of larger devices, which aided in restoring volume and maintaining breast contour. Three (2.2%) patients requested removal of the device.Conclusions:BioZorb implantation can be a safe and useful oncoplastic technique for restoring volume with BCS. Large-volume lumpectomies can be performed without contouring defects using the device. An unexpected secondary benefit of the device may be scaffolding for wound contraction.

Abstract PS15-19: Preoperative selection of patients with early-stage invasive breast cancer for intraoperative radiation therapy (IORT): A single-institution experience

Abstract Purpose/Objective: Intraoperative radiation therapy (IORT) is a form of accelerated partial breast irradiation (APBI) delivered at the time of lumpectomy for early-stage breast cancer. Upfront selection of patients based on favorable preoperative characteristics is important to achieve good outcomes. Here we present our single-institution experience in the management of invasive breast cancer with IORT. We focused on the classification of patient suitability for IORT by the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines using preoperative and postoperative clinicopathologic factors, as well as treatment outcomes and recurrences. Materials/Methods: We reviewed our institutional prospective registry database (AAAJ8512) to identify patients with biopsy-proven invasive breast cancer treated with breast IORT between 9/2013 and 4/2020 using the Zeiss Intrabeam™. Patients received a single dose of 20Gy delivered to the lumpectomy cavity surface at the time of planned surgery. We excluded patients from analysis with prior radiation to the breast, or triple negative disease at initial diagnosis. We reviewed preoperative and postoperative clinicopathologic factors to determine each patient’s ASTRO APBI suitability (suitable, cautionary or unsuitable) based on the 2017 consensus guidelines. Results: 237 patients were treated with IORT for early stage breast cancer. Median age was 67 years (range 44-94 years). Median extent of disease by conventional imaging was 1.0 cm (range 0 - 3.0cm). 51/103 (49.5%) patients with heterogeneously or extremely dense breasts underwent a MRI preoperatively. Based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable according ASTRO APBI guidelines, 46 (19.4%) cautionary and no patients were unsuitable. APBI group suitability changed in 95 (40.1%) patients based on final pathology from the time of lumpectomy, summarized in Table 1. 17 (7.2%) patients underwent re-excision for close or positive margins. 39 (16.5%) patients received additional adjuvant whole breast radiotherapy including 10/18 (56%) of unsuitable patients. Of 212 (89.5%) patients who initiated hormone therapy (HT), 191 (80.6%) were compliant at last follow up. Median follow-up for all patients was 38.2 months (0.4 - 74.5). Five (2.1%) patients experienced ipsilateral breast tumor recurrence, 1 (0.4%) patient experienced new contralateral breast cancer, and 2 (1.6%) patients experienced distant recurrence with the median time to event of 27.8 months (range 6.3-50.4). Of the 5 patients with ipsilateral breast tumor recurrence, 2 (0.8%) were true local recurrences &amp;lt;2cm from the initial lumpectomy bed with the same histology as initial tumor, both cases were cautionary risk and one declined HT, 3 (1.3%) were new breast primaries occurring &amp;gt;2cm from lumpectomy bed with a different histology. Conclusion: Breast IORT is an attractive cost-effective option for women with early stage breast cancer, and our 3-year true local recurrence rate is 0.8%. Optimal patient selection is key based on preoperative characteristics. Patients who become unsuitable or cautionary for APBI based on final pathology should be considered for additional adjuvant therapy. Table 1ReasonASTRO APBI Pre-Op Suitability#SizeER (-)AgeT2ILCSuitable191Cautionary46114101122Unsuitable0ASTRO APBI Post-Op Suitability Change#SizeClose MarginsPositive MarginsLVIMultifocalILCEICSuitable to Cautionary7792023211124Suitable to Unsuitable12111Cautionary to Unsuitable624Abbreviations: ER = Estrogen Receptor; ILC = Invasive Lobular Carcinoma; LVI = Lymphovascular Invasion; EIC = Extensive Intraductal Component Citation Format: Andrea M Brown, Christine Chin, Eileen Connolly, Roshni Rao, Bret Taback, Lisa Wiechmann. Preoperative selection of patients with early-stage invasive breast cancer for intraoperative radiation therapy (IORT): A single-institution experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-19.

TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and arenotably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

The Effect of Oncoplastic Reduction on The Incidence of Post-Operative Lymphedema in Breast Cancer Patients Undergoing Lumpectomy

In patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) may be associated with increased radiation exposure and a different complication profile than those without macromastia. The oncoplastic reduction mammoplasty (ORM) procedure includes breast reduction at the time of BCS. The purpose of this study is to determine if women with macromastia who undergo ORM have a different complication profile compared to those who undergo BCS followed by RT. We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2017. Chronic breast lymphedema (CBL) was defined as swelling that persisted >1-year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate various patient factors and treatment outcomes in women with BV ≥1300 cc compared to <1300 cc. These same factors were compared in women who underwent ORM vs. BCS. Multivariate regression analysis was used to evaluate factors associated with ≥1 complication. Logistic regression was performed to identify factors associated with the development of CBL. The total population included 785 patients, of which 28 (3.6%) underwent ORM and 757 (96.4%) underwent BCS. The total population was stratified into two groups, in which 289 (36.8%) patients had BV ≥1300 cc and 496 (63.2%) patients had a BV <1300 cc. Compared to patients with BV<1300 cc, those with BV ≥1300 cc had a higher percentage of African Americans (52.6% vs. 41.5%, P = 0.002), higher median BMI (34.96 vs. 27.87, P<0.001), higher incidence of diabetes (39.8% vs. 27.2%, P<0.001), higher incidence of hypertension (75.4% vs. 63.1%, P<0.001), and higher incidence of CBL (12.5% vs. 4.2%, P<0.001). Compared to BCS patients, ORM patients with BV ≥1300 cc had increased incidence of CBL (36.4% vs. 11.5%, P = 0.035). Logistic regression showed that the incidence of ≥1 complication was associated with BMI, presence of SLNB, and the number of lymph nodes removed in either SLNB or ALND. However, factors such as ORM and BV were not associated with an increased risk of ≥1 complication. Logistic regression demonstrated that having a BV ≥1300 cc was associated with 2.5 times increased odds of CBL compared to those with BV <1300 cc. Even though those who underwent ORM did not change the risk for CBL for the entire cohort, ORM patients with BV ≥1300 had a higher risk of CBL. Ultimately, logistic regression demonstrates that ORM does not increase the risk of CBL when adjusting for BV. In conclusion, axillary surgery contributed most significantly to the incidence of having ≥1 complication. However, BV was associated with an increased risk of CBL, regardless of the presence of ORM. Therefore, women with BV ≥1300 cc should be offered ORM at the time of lumpectomy in order to reduce their future risk of CBL.

Magnetic seed localisation for non-palpable lesions in patients undergoing breast conservative surgery

Purpose: Breast-conservative surgery is the standard procedure for breast cancer when tumour resection does not lead to significant cosmetic sequelae. The usual technique to locate non-palpable lesions is the wire-guided localization (WGL). However, the WGL may migrate and cause interference with the electro cautery. The placement of the WGL has to be performed on the day before or the day of the surgery, causing organizational problems. To optimize care pathway and increase ambulatory activity, the authors studied the feasibility and efficacy of a 5-mm iron seed MAGSEED. Materials and Methods: During four months, 20 seeds were placed in 19 patients undergoing a lumpectomy for non-palpable breast lesions. The evaluation questionnaire was filled by radiologists, surgeons, and patients. Results: All clips were detected. The radiological and surgical team found the MAGSEED simple and intuitive. Placement was done by ultrasound and stereotaxic guidance up to 15 days before surgery. Time of lumpectomy was reduced to an average of 11 minutes. Patients’ pain level was low (2/10). Conclusion: The use of MAGSEED for the detection of non-palpable breast lesions is simple, safe, and feasible. A comparative randomized prospective study should be performed between MAGSEED and WGL to study the medico-economic outcomes and the surgical and radiological benefits of the magnetic seed.

(OA27) Outcome in Patients Treated With Partial Breast Reconstruction or Bilateral Reduction Mammoplasty at the Time of Breast Conserving Surgery (BCS) Followed by Whole Breast Radiation Therapy (WBRT)

Lumpectomy/ partial mastectomy may result in asymmetry of the treated breast relative to the unaffected breast. Volume loss is the most common cause of the negative cosmetic outcome in patients undergoing BCS. To help improve cosmetic results the practice of breast oncoplasty at the time of lumpectomy ± sentinel node surgery is gaining popularity. In this paper, we report our experience on patients who underwent autologous flap partial breast reconstruction or bilateral reduction mammoplasty at the time of BCS. Postoperatively, all patients received WBRT. The objective of the study was to evaluate cosmetic outcomes and local control. In addition, we sought to study the incidence for the recommendations of BIRADS 3 or 4, and fat necrosis on follow up mammograms and sonograms. In this retrospective study, we identified 24 breast cancer patients who at the time of BCS either underwent partial breast reconstruction using autologous flap or had bilateral reduction mammoplasty. Postoperatively, all patients received WBRT to a dose ranging from 50.4Gy to 60Gy. Adjuvant systemic therapy was prescribed at the discretion of the treating oncologist. In follow up, all patients were seen at regular intervals by the multidisciplinary team, and mammograms and directed sonograms were obtained at scheduled intervals. A total of 27 breasts in 24 patients (3 bilateral) are included in this review. The median follow up is 48 months (range: 4 months to 79 months). The median age is 52 years (range: 29 to 71 years). The pathologic stage distribution was: 7 stage 0, 13 stage I, 5 stage II, and 2 had stage ypT0N0M0 having presented with clinical stage IIB and undergone BCS following neoadjuvant therapy. All but 1 patient had negative resections margins. The median number of excisions to achieve clear margins was 2 (range 1 to 3). Fifteen patients underwent bilateral reduction mammoplasty, while 9 had either thoracodorsal artery perforator flap (TDAP), lateral intercostal artery perforator flap (LICAP), or other autologous free flaps. Twenty patients also received systemic chemotherapy and/or hormonal therapy. Cosmetic results in the majority were excellent/very good. In follow up we observed that 4 patients underwent additional revisions for cosmetic indications; and 3 of the 4 patients were among those who had partial breast reconstruction using free-flaps. Follow up mammography noted recommendation of BIRADS 3 and 4 in 3/27 (11.1%) and 2/27 (7.4%) breasts, respectively. Additionally, 5/27 (18.5%) had radiographic evidence of fat necrosis. No patient has developed a local recurrence. In the multidisciplinary care of breast cancer the integration of plastic surgery procedures is increasingly gaining acceptance. We observed that partial breast reconstruction as an adjunct to BCS prior to WBRT results in excellent cosmetic result and local control. Radiographically, the incidence of fat necrosis was the most common finding and the recommendation for BIRADS 4 was low. In select cases, partial breast reconstruction at the time of BCS prior to WBRT may be a reasonable approach to offset the volume loss of an extensive lumpectomy.

Oncoplastic Breast Reduction Technique and Outcomes: An Evolution over 20 Years.

Reduction mammaplasty at the time of lumpectomy is a good option in women with breast cancer and macromastia. We critically evaluated refinements and outcomes of this technique. A prospectively maintained database was reviewed of all women with breast cancer who received lumpectomy and reduction mammaplasty at our institution from 1994 to 2015. Patients' demographics were reviewed. Preoperative and postoperative patient satisfaction (BREAST-Q) was determined. Comparisons were made between early and recent cases. There were 353 patients included. Average age was 54 (range, 21 to 80 years), with the largest number having stage I disease [n = 107 of 246 (43.5 percent)]. Average lumpectomy specimen was 207 g (range, 11.6 to 1954 g) and total reduction weight averaged 545 g (range, 21 to 4102 g). Tumor size averaged 2.02 cm (range, 0.00 to 15.60 cm). The positive margin rate was 6.2 percent (n = 22). Completion mastectomy rate was 9.9 percent (n = 35). Overall complication rate was 16 percent. The recurrence rate was 5.2 percent (n = 10 of 192) at a mean follow-up of 2 years (range, 2 months to 15 years). Resection weights greater than 1000 g were associated with having a positive margin (16.7 percent versus 5.0 percent; p = 0.016), and tended to be associated with having a completion mastectomy (p = 0.069). Positive margin and completion mastectomy rates have been lower in the past 10 years. Over 1 year postoperatively, women reported increased self-confidence (p = 0.020), feelings of attractiveness (p = 0.085), emotional health (p = 0.037), and satisfaction with sex life (p = 0.092). The oncoplastic reduction technique is effective and results in improved patient-reported outcomes. Resections over 1000 g are associated with a higher incidence of positive margins and may increase the risk for completion mastectomy. Outcomes have improved with experience and refinement in technique.

Abstract P3-13-04: Use of an absorbable implant to mark the lumpectomy cavity: Initial report of 300 patients in a multi-center registry database

Abstract Objective: Increased use of oncoplastic procedures makes it difficult to distinguish the lumpectomy margins from seroma fluid. Many side effects of radiation therapy are due to overestimated treatment volumes due to seroma based planning. A novel 3-dimensional (3D) absorbable device sutured to the lumpectomy tumor bed allows greater precision in targeting of the margins while avoiding normal tissues. A multi-center clinical registry was established to assess use of this device over time. This initial report of the first 300 patients provides insight into patient selection, tumor characteristics, method of implantation and initial outcomes. Methods: A bioabsorbable 3D implantable marker with a fixed array of 6 titanium clips was sutured to the site of the excised breast cancer during lumpectomy with or without oncoplastic closure techniques. The framework of the implant resorbs slowly over time, while the clips remain permanently. The marker was utilized for boost or partial breast irradiation (PBI) planning or treatment targeting. To date the registry has accrued 300 patients from 12 centers. Data includes patient demographics, breast size, tumor characteristics, surgical and radiotherapy techniques, cosmesis and follow-up. Results: Data on 300 patients with median follow-up 10.4 months was analyzed. Median age was 64.4 years, 83% of women were postmenopausal and 10% had comorbidities. Breast size was evenly distributed between cup size B, C and &amp;gt;D. Cancer histology was in-situ (20%), invasive ductal (62%), invasive lobular (9%) and others (10%) measuring T1 (80%) and T2 (20%). Laterality and tumor location within the breast were typical. Most patients had oncoplastic rearrangement (74%) at the time of lumpectomy. Re-excision (including mastectomy for extensive disease) occurred in 14% of patients. Infections occurred in 2% of patients and in one patient the device was removed during surgical debridement of the postoperative infection. No devices have been removed during follow-up due to misplacement or patient-generated concerns. No cancer recurrences have been reported. In most cases, size of the device reflected size of the tumor with the 2X2cm (47%) and 2X3cm (32%) devices used most often. The device was utilized by radiation oncologists for boost or PBI planning and treatment. Data on ease of setup and boost planning is being collected. Early reports regarding cosmetic appearance show a trend for excellent or good cosmesis as judged separately by both physicians and patients (93% and 92%). Conclusions: A novel 3-dimensional absorbable device sutured into the tumor bed provides clarity in radiation targeting of tissues at greatest risk while sparing adjacent normal tissues mobilized during surgery. This initial report of a multi-center clinical registry on over 300 patients characterizes patient selection, treatment methods and follow-up. Ongoing collection of additional data, regarding radiation regimen, cosmesis and patient satisfaction, have been accumulated and provide insight regarding clinical attributes of this implantable marker. Citation Format: Kaufman CS, Cross MJ, Goyal S, Barone J, Devisetty K, Dekhne NS, Edmonson D, Gass JS, Graham CL, Hong RL, Patton BJ, Phillips RF, Schonholz SM, Smith LA, Tafra L, Smith AB, Dilworth J. Use of an absorbable implant to mark the lumpectomy cavity: Initial report of 300 patients in a multi-center registry database [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-04.

Frequency of whole breast radiation therapy after intraoperative radiation therapy due to criteria identified by lumpectomy

PurposeFor selected early breast cancers, intraoperative radiation therapy (IORT) at the time of lumpectomy can be an efficient alternative to fractionated whole breast radiation therapy (WBRT). However, some patients are later recommended WBRT after IORT due to surgical pathologic findings. To understand risk factor identification rates triggering WBRT recommendation, we analyzed adverse prognostic features based on multiple international criteria for suitability for accelerated partial breast irradiation. Methods and MaterialsWe performed a single-institution retrospective review of all 200 nonrecurrent invasive breast carcinomas that received IORT in 20 Gy to the tumor cavity using a 50 kV photon applicator between January 2011 and December 2015. IORT eligibility was based on the 2009 accelerated partial breast irradiation Consensus Statement from the American Society for Radiation Oncology (ASTRO). IORT was offered as the sole radiation modality to patients meeting 0–1 “cautionary” and no “unsuitable” criteria before lumpectomy. WBRT was recommended after IORT when 2+ cautionary and/or 1+ unsuitable criteria were met after accounting for resection pathology. We recalculated WBRT recommendation rates using initial and reresection margins for ASTRO consensus, Groupe Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology recommendations, and TARGeted Intraoperative radioTherapy vs. Postoperative Radiotherapy trial “prepathology” stratum protocol. ResultsDepending on the selection criteria chosen, rates of WBRT recommendation can vary from 4.5% to 33%. ConclusionsWBRT recommendation rates of 30–33% after lumpectomy and IORT are observed when the WBRT indication is a single ASTRO cautionary/unsuitable, Groupe Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology intermediate/high-risk criterion, or TARGeted Intraoperative radioTherapy vs. postoperative radiotherapy trial protocol recommendation. Alternatively, allowing for re-excision to clear margins and accepting one ASTRO cautionary factor lowered the rate of WBRT recommendation to 9.5%.

Lumpectomy specimen margins are not reliable in predicting residual disease in breast conserving surgery

BackgroundIn breast conserving surgery, the concordance between lumpectomy margin (LM) status and the status of the corresponding lumpectomy cavity remains uncertain. MethodsWe analyzed pathology reports of lumpectomies from 2004 to 2006. We included those which contained both ink-directed LM and complete (≥4) separate corresponding shaved cavity margins (SCMs). SCM pathology was used as a surrogate for lumpectomy cavity status, to determine the predictive value of LM for residual disease. ResultsPathology from 1,201 pairs of LM and SCM from 242 patients was compared. LM status predicted corresponding lumpectomy cavity status with 50.9% sensitivity, 69.5% specificity, 35% positive predictive value, and 81.4% negative predictive value, giving an overall accuracy of 64.9%. ConclusionsOriented LMs are not reliable for predicting lumpectomy cavity status, and therefore not reliable for directing re-excision. Taking complete, oriented SCMs at the time of lumpectomy may improve accuracy compared with traditional LM assessment.

Identifying the surgical cavity following oncoplastic breast surgery.

81 Background: Oncoplastic surgery (OPS) has improved outcomes for partial mastectomy. However, tissue rearrangement poses challenges in the post-operative management of these patients. In most cases, these patients will require post-operative radiotherapy. Accurately visualizing the surgical cavity can be particularly troublesome in patients who have oncoplastic closure of the resection cavity. Recent advances have made it feasible to perform external beam radiation using advanced methods, but these are not commonly used for breast cancer. This is due to the difficulty in identifying the exact area of the surgical site. In this series of patients, a novel method for marking the surgical site when using oncoplastic techniques was evaluated. Methods: 65 patients had a 3-D tissue marker implanted at the time of lumpectomy. All patients were candidates for partial mastectomy and local breast reconstruction using OPS. Post-operative treatment plans for radiation and/or adjuvant chemotherapy were completed. Patients were evaluated with standard breast imaging methods for treatment planning. Results: The marker was easily identified and clearly delineated within the lumpectomy cavity. It provided 3-D characterization of the borders surrounding the cavity, and was easily distinguished from seroma and other tissue changes. Respiratory motion was easily tracked using the device making it possible to use IMRT and accelerated protocols. Use of the marker resulted in treatment volumes that were reduced by an average of 50% when compared to standard methods. In appropriate patients when the marker facilitated an accelerated protocol, total treatment time was decreased to 5-7 days. No complications were reported, and overall patient outcomes were excellent. Conclusions: This novel 3-D marker was consistently visualized without difficulty, was readily incorporated into standard practices and had appreciable benefits when designing optimal treatment plans. Its unique features were helpful in all cases, but particularly useful when using oncoplastic techniques to reconstruct the breast with local tissue flaps.

Identifying the surgical cavity following oncoplastic surgery: Utility of a novel tissue marker.

76 Background: Oncoplastic surgery has helped improve outcomes following partial mastectomy. However, in most cases, patients still require post-operative radiotherapy, which can cause significant complications. While recent advances have made it feasible to perform external beam radiation in a more targeted and accelerated fashion, these methods are not commonly used in the treatment of breast cancer. This is due to the difficulty in identifying the margins of the surgical site, and can be particularly challenging with oncoplastic surgery (OPS). In this pilot study, we evaluated a new method for marking the margins of the surgical cavity when using oncoplastic techniques. Methods: 15 patients were selected to have a 3-D tissue marker implanted at the time of lumpectomy. All patients were candidates for partial mastectomy, sentinel lymph node biopsy and breast reconstruction using OPS. Post-operative treatment plans including radiation and/or adjuvant chemotherapy were completed as recommended. Patients were followed and imaged with standard breast imaging following completion of their treatment. Results: The marker was easily identified and clearly delineated the margins of the lumpectomy cavity. It allowed for 3-D characterization of the borders surrounding the cavity, and it was easily distinguishable from the seroma and other surgical tissue changes. Respiratory motion was easily tracked using the device making it possible to apply advanced radiation treatment methods such as IMRT and accelerated protocols. When compared to conventional methods of determining the target area, use of the marker resulted in treatment volumes that were reduced by &gt;60%. In appropriate patients, the marker also facilitated the use of an accelerated protocol, decreasing total treatment time from 6 weeks to 5 days. No complications were reported. Conclusions: This novel 3-D marker was consistently visualized, was readily incorporated into standard and advanced dose planning methods, and had appreciable benefits when designing optimal treatment plans. Its unique features were also helpful when using oncoplastic techniques, and proved valuable for long-term follow-up using standard methods of breast imaging.

Breast interstitial implant with rigid needles and plastic tubes: Plesiobrachytherapy

Breast brachytherapy (BT) with rigid needles was the first way to boost the bed tumor avoiding skin. Several long-term studies have shown that HDR-BT can be used in 1–2 fractions in one day, on an outpatient basis, which is far more comfortable than LDR-BT. The needles, fixed with templates, allow an excellent dose-homogeneity with the optimization of HDR. Clips are useful to delineate the tumor bed, performing a CT for dosimetry, but it is not easy to draw it when an open cavity has disappeared. Most studies define the tumor bed by clinical assessment, according to themammography, patient and surgeon’s initial description, and palpation. The target is defined as the tumor bed plus a margin of 1–2 cm, avoiding 1 cm from skin and from the entrance of the needles. If the tumor location is not clearly defined, a larger implant is used to avoid a geographical miss. The shape of the breast can be modified if needed because the templates keep the needles in place. Dosimetry calculations are theoretical, making a reconstruction of catheters, because the distance between needles is constant. The total procedure is easy and quick, takes around 2–3h, and is called “Fast-boost”. Historically, like rigid needles, breast brachytherapy with plastic tubes is performed in the operating room. This was either done at the time of lumpectomy or as a separate procedure following lumpectomy with pathologic evaluation completed and information available. Although there are different techniques of catheter placement, general guidelines of catheter placement are consistent. Stainless steel guide needles are introduced into the breast tissue at the appropriate locations. Once its placement is complete they are replaced with button-ended flexible after loading plastic tubes and secured with proper fixation buttons. Implant construction is governed by basic breast brachytherapy principles with the goal of optimizing target coverage and dose homogeneity and it is easily when it is done in intra – operative time because we can see tumor bed and discuss with surgeon tumor localization. For both, intra or postoperative implants, dosimetric planning can be managed with a two or three dimensional planning process utilizing dummy source strands in each catheter with subsequent orthogonal films or more recently using a CT. The main advantages of plastic tube are that the implant is probably better tolerated by the patient, but is more difficult to contain the optimal geometry (parallelism, inter catheter spacing and distance to the overlying skin). The plesiobrachytherapy consist of an applicator containing an array of radioactive sources usually designed to deliver a uniform doses distribution to skin. It can be used only for very superficial lesions (up to 5mm target depth). The applicator must be adapted to the topography of the tumor. Irregular and curved areas can be treated. Fixation and immobilization are crucial. Indication is breast cancer recurrences after mastectomy (inoperable) in already irradiated areas. The guide system consisted of plastic tubes inserted at 1.5 cm intervals into flexible silicone plates that were applied to skin surface to maintain the actives lines 0.5 cm above the skin surface. The high dose sleeves surrounding the actives lines were contained within the thickness of the silicone plate. The length of the sources has to be adapted to the length of the PTV, calculated previously to the application. Computations for the doses desired are carried out, and optimal placement of the

Phase 2 study of pre‐excision single‐dose intraoperative radiation therapy for early‐stage breast cancers

Intraoperative radiation therapy (IORT) allows delivery of high-dose radiation at the time of lumpectomy, potentially sparing adjuvant daily radiation. A phase 2 study of pre-excision IORT was performed for early-stage breast cancer. Patients ≥ 48 years of age with invasive ductal carcinoma, ≤ 3 cm, and clinically node-negative were eligible for this study, which was approved by institutional review board. Ultrasound was used to select electron energy and cone size to cover the tumor plus 1.5- to 2.0-cm lateral margins and 1-cm-deep margins (90% isodose). Fifteen Gy was delivered with a Mobetron irradiator, and immediate needle-localized partial mastectomy followed. Local event results were updated using the Kaplan-Meier method. A total of 53 patients received IORT alone. Median age was 63 years, and median tumor size was 1.2 cm. Of these, 81% were positive for estrogen receptor or progesterone receptor, 11% were positive for human epidermal growth factor receptor 2, and 15% were triple-negative. Also, 42%, 49%, and 9% would have fallen into the Suitable, Cautionary, and Unsuitable groups, respectively, of the American Society of Therapeutic Radiation Oncology consensus statement for accelerated partial breast irradiation. Median follow-up was 69 months. Ipsilateral events occurred in 8 of 53 patients. The 6-year actuarial rate of ipsilateral events was 15% (95% confidence interval = 7%-29%). The crude event rate for Suitable and Cautionary groups was 1 of 22 (5%) and 7 of 26 (27%), respectively. Overall survival was 94.4%, and breast cancer-specific survival was 100%. The rate of local events in this study is a matter of concern, especially in the Cautionary group. On the basis of these findings, pre-excision IORT, as delivered in this study, may not provide adequate local control for less favorable early-stage breast cancers.

Tracking the dynamic seroma cavity using fiducial markers in patients treated with accelerated partial breast irradiation using 3D conformal radiotherapy

The purpose of the present study was to perform an analysis of the changes in the dynamic seroma cavity based on fiducial markers in early stage breast cancer patients treated with accelerated partial breast irradiation (APBI) using three-dimensional conformal external beam radiotherapy (3D-CRT). A prospective, single arm trial was designed to investigate the utility of gold fiducial markers in image guided APBI using 3D-CRT. At the time of lumpectomy, four to six suture-type gold fiducial markers were sutured to the walls of the cavity. Patients were treated with a fractionation scheme consisting of 15 fractions with a fractional dose of 333 cGy. Treatment design and planning followed NSABP∕RTOG B-39 guidelines. During radiation treatment, daily kV imaging was performed and the markers were localized and tracked. The change in distance between fiducial markers was analyzed based on the planning CT and daily kV images. Thirty-four patients were simulated at an average of 28 days after surgery, and started the treatment on an average of 39 days after surgery. The average intermarker distance (AiMD) between fiducial markers was strongly correlated to seroma volume. The average reduction in AiMD was 19.1% (range 0.0%-41.4%) and 10.8% (range 0.0%-35.6%) for all the patients between simulation and completion of radiotherapy, and between simulation and beginning of radiotherapy, respectively. The change of AiMD fits an exponential function with a half-life of seroma shrinkage. The average half-life for seroma shrinkage was 15 days. After accounting for the reduction which started to occur after surgery through CT simulation and treatment, radiation was found to have minimal impact on the distance change over the treatment course. Using the marker distance change as a surrogate for seroma volume, it appears that the seroma cavity experiences an exponential reduction in size. The change in seroma size has implications in the size of the CTV, PTV, and percent of normal breast tissue irradiated when using 3D-CRT.