Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

PURPOSE: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation with interstitial multicatheter brachytherapy by a cooperative group of institutions. METHODS: From 1992 to 2013, a total of 1356 patients were treated with breast-conserving surgery and adjuvant accelerated partial breast irradiation using interstitial multicatheter brachytherapy. A total of 1131 patients had >1 year of data available to assess oncologic and cosmesis outcomes. Median age was 59 years old (range 22-90 years). Histologies treated included 1005 (73 %) invasive ductal carcinoma and 240 (18 %) ductal carcinoma-in situ. T stages were 18 % Tis, 75 % T1, and 8 % ≥T2. Nodal status was 73 % N0 and 6 % N1a. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was positive in 83, 70, and 6 %, respectively. Cox multivariate analysis for local control was performed using histology, age, estrogen receptor status, tumor size, grade, margin, and nodal status. RESULTS: The mean (SD) follow-up was 6.9 years (4.3). The 10-year actuarial risk (95 % confidence interval) of an ipsilateral breast tumor recurrence was 7.6 % (5.6-10.1). Other 10-year actuarial risks (95 % confidence interval) were regional failure 2.3 % (1.4-3.7), distant metastasis 3.8 % (2.5-5.7), cause-specific survival 96.3 % (94.2-97.6), overall survival 86.5 (83.0-89.3), and new contralateral cancers 4.6 % (3.0-6.9). On multivariate analysis, high grade (hazard ratio 2.81) and positive margin status (hazard ratio 18.42) were the only two significant variables associated with an increased risk of local recurrence. Physician-reported cosmesis was excellent/good in 84 % (98 of 116) of patients with >5 years of follow-up. CONCLUSIONS: This is the largest report of outcomes with interstitial breast brachytherapy. This treatment resulted in excellent long-term local control and cosmesis outcomes.

Multi-institutional experience using the MammoSite radiation therapy system in the treatment of early-stage breast cancer: 2-year results.

PURPOSE: To present a retrospective multi-institutional experience of patients treated with the MammoSite radiation therapy system (RTS). METHODS AND MATERIALS: Nine institutions participated in a pooled analysis of data evaluating the clinical experience of the MammoSite RTS for delivering accelerated partial breast irradiation. Between 2000 and 2004, 483 patients were treated with the MammoSite RTS to 34 Gy delivered in 10 fractions. Treatment parameters were analyzed to identify factors affecting outcome. RESULTS: Median follow-up was 24 months (minimum of 1 year). Overall, infection was documented in 9% of patients, but the rate was only 4.8% if the catheter was placed after lumpectomy. Six patients (1.2%) experienced an in-breast failure; four failures occurred remote from the lumpectomy site (elsewhere failure). Cosmetic results were good/excellent in 91% of patients. Treatment parameters identified as significant on univariate analysis were tested in multivariate regression analysis. The closed-cavity placement technique significantly reduced the risk of infection (p = 0.0267). A skin spacing of <6 mm increased the risk of severe acute skin reaction (p = 0.0178) and telangiectasia (p = 0.0280). The use of prophylactic antibiotics reduced the risk of severe acute skin reaction (p < 0.0001). The use of multiple dwell positions reduced the risk of severe hyperpigmentation (p = 0.0278). Infection was associated with an increased risk of fair or poor overall cosmesis (p = 0.0009). CONCLUSIONS: In this series of patients, the MammoSite RTS seems to have acceptable toxicity rates and cosmetic outcomes, comparable to those with whole-breast radiotherapy. On the basis of these data, the closed-cavity placement technique, use of prophylactic antibiotics, use of multiple dwell positions, and a minimum skin spacing of 6 mm seem to improve patient outcome.

Outcomes by molecular subtype after accelerated partial breast irradiation using single-entry catheters.

PURPOSE: Tumor biology is being recognized as an important indicator of prognosis and risk of locoregional recurrence. Here, we determine actuarial recurrence rates by approximated molecular subtype for women treated with single-entry catheter accelerated partial breast irradiation (sAPBI). METHODS AND MATERIALS: One thousand four hundred eighty-six women with invasive cancer having known ER, PR, and Her2 status and at least 1-year of followup were treated using MammoSite, Contura, or SAVI sAPBI from 2002 to 2014 at our institution. Actuarial recurrence rates were determined for the following four approximated molecular subtypes using the Kaplan-Meier method: luminal A (n = 1081), luminal B (n = 164), Her2 (n = 123), and triple-negative breast cancer (TNBC; n = 118). RESULTS: With a median followup time of 3.3 years (range 1-13.6 years), the 5-year in-breast tumor recurrence rate was 2.6% overall, 2.1% for luminal A, 1.5% for luminal B, 4.9% for Her2, and 5.4% for TNBC. Luminal A and B subtypes, as compared with the more aggressive Her2 and TNBC subtypes combined, demonstrated lower 5-year in-breast tumor recurrence (2.1% vs. 5.1%, p = 0.021). The 5-year regional nodal recurrence rate was 1.4% overall, 1.4% for luminal A, 0% for luminal B, 1% for Her2, and 4.2% for TNBC. The 5-year locoregional control is 97.3% for luminal breast cancers and 93.8% for the more aggressive Her2 and TNBC subtypes collectively. CONCLUSIONS: Luminal cancers demonstrated excellent 5-year locoregional control with sAPBI. Although caution should be used when treating patients with the more aggressive Her2 and TNBC subtypes, these subtypes have demonstrated higher LRR with mastectomy and whole-breast irradiation. Further randomized comparisons are needed to determine the optimal treatment for these higher risk patients.

Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

OBJECTIVES: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. MATERIALS AND METHODS: From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. RESULTS: The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. CONCLUSIONS: Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients.

Preliminary results and evaluation of MammoSite balloon brachytherapy for partial breast irradiation for pure ductal carcinoma in situ: a phase II clinical study.

BACKGROUND: This report presents the preliminary results and evaluation of the MammoSite balloon catheter (MammoSite Radiation Therapy System; Cytyc Corporation, Marlboro, MA) as the sole method of delivering partial breast irradiation to the lumpectomy bed with breast-conserving surgery in patients with pure ductal carcinoma in situ (DCIS). METHODS: Twelve institutions are participating in this phase II clinical study. A total of 133 patients have been enrolled and 100 patients have successfully completed the prescribed radiation therapy. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose rate brachytherapy. Patients who met the following criteria were selected for enrollment into the study: age 45 years or older, unicentric pure DCIS, mammographic lesion of 3 cm or less, negative margins as defined by 1 mm or more, postoperative final gross pathologic size of tumor of 5 cm or less, clinically node negative, and a postlumpectomy mammogram showing the absence of any residual suspicious microcalcifications. The placement of the MammoSite catheter was performed either at the time of the lumpectomy or postlumpectomy. The minimum distance from the balloon surface to the surface of the skin is greater than 5 mm. Data collection points are at time of enrollment, time of implant, 3 months, 6 months, and then yearly at 1- to 5-year follow-up visits. Data collected are local control rates, cosmetic outcome using the Harvard Scale, toxicities, serious adverse events, disease-free survival, cause-specific survival, and contralateral breast failure. The Van Nuys Prognostic Index scores were calculated for each patient. Local recurrence is defined as either invasive or noninvasive recurrence within the target volume. Ipsilateral elsewhere recurrence is defined as either an invasive or noninvasive recurrence occurring outside of the target volume in the previously treated breast. This recurrence is classified as a new primary tumor. RESULTS: The mean follow-up period was 9.5 months (range, 1-24 mo). The MammoSite catheter was explanted for the following reasons: inadequate skin distance (5.1%; 6 of 117), poor cavity conformance (5.1%; 6 of 117), positive margins (2.6%; 3 of 117), final histology (.85%; 1 of 117), and physician decision (.85%; 1 of 117). Of the patients in whom the MammoSite was explanted because of skin spacing or cavity conformance, 50% were at sites of new users (institutions that have placed fewer than 10 Mammosite catheters). Cosmetic results were rated as excellent in 63%, good in 35%, and fair in 2% in the 86 patients with a follow-up visit. Two patients were diagnosed with an ipsilateral local recurrence, 1 outside of the target volume and 1 true recurrence/marginal miss. One patient was diagnosed at 8 months and the other was diagnosed at 11 months. Both of these ipsilateral failures were DCIS. The Van Nuys Prognostic Index of these 2 patients was 9 and 8, respectively. Data collected showed the mean age at placement was 60.8 y, mean tumor size was 10.6 mm, mean actual closest surgical margin was 6.8 mm (range, .1-40 mm), a re-excision rate of 35%, postlumpectomy placement was 71%, and the mean skin-to-balloon surface distance was 13 mm with 89% > or =7 mm. No serious adverse events were reported. The infection rate was 4.0%. CONCLUSIONS: Accelerated partial breast irradiation delivered with the MammoSite balloon was clinically successful in patients entered into a phase II clinical study with pure DCIS, with results comparable with other studies reported in the literature that have evaluated use of the MammoSite balloon brachytherapy for delivery of radiation therapy in early breast cancers. Inadequate skin distance and poor cavity conformance were the main factors limiting the use of the MammoSite device. Cosmetic results were good to excellent in 98%. There have been 2 ipsilateral breast recurrences.

Updated feasibility and reproducibility results of multi-institutional study of noninvasive breast tumor bed boost.

PURPOSE: To report updated feasibility and reproducibility results for high-dose-rate noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT) in the setting of expanded patient and treatment facility number. METHODS AND MATERIALS: Fifteen independent community-based and academic centers reported 518 early-stage breast cancer patients from July 2007 to February 2015 on a privacy-encrypted online data registry. All patients' treatment included lumpectomy followed by combination of WBRT and NIBB. NIBB was completed with commercially available (AccuBoost, Billerica, MA) mammography-based system using high-dose-rate 192Ir emissions along orthogonal axes. Harvard scale was used to grade cosmesis. RESULTS: Total patient cohort had median followup of 12 months (1-75 months) with subset of 268 having available cosmesis. Greater than 2- and 3-year followup was 29% and 14%, respectively. Entire cohort had 97.4% excellent/good (E/G) breast cosmesis and freedom from recurrence of 97.6% at the final followup. WBRT timing with respect to NIBB delivery demonstrated no statistically significant difference in E/G cosmesis. Achieved E/G cosmesis rate was also not statistically significant (χ2p-value = 0.86) between academic and community institutions with 97.8% vs. 96.6%. CONCLUSIONS: NIBB represents an alternative method for delivery of breast tumor cavity boost that has shown feasibility in a diverse group of both academic and community-based practices with reproducible early cosmesis and tumor control results. Recommendations are updated noting ideal timing of boost delivery likely to be before or early during WBRT given equal cosmesis and less documented treatment discomfort.

Descriptions and outcomes of insertion techniques of a breast brachytherapy balloon catheter in 1403 patients enrolled in the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial.

BACKGROUND: The use of the MammoSite brachytherapy balloon catheter is 1 option for the delivery of accelerated partial breast irradiation during breast cancer therapy. The device can be inserted into the breast using 3 different techniques. This report describes these methods of insertion and correlates the technique with outcome data collected in a multi-institutional registry trial. METHODS: In the registry trial, MammoSite catheters were inserted either (1) at the time of lumpectomy into an open cavity, (2) after surgery with ultrasound guidance through a separate small lateral incision into a closed cavity, or (3) after surgery by entering directly through the lumpectomy wound (the scar entry technique). Device placement techniques in 1403 patients with early stage breast cancer treated at 87 institutions by 223 different investigators were documented in the registry. Data collected included number of cases of each technique, age of patient, tumor size, skin spacing, catheter pull rates and reasons, infection, radiation recall, cosmesis, and recurrence. RESULTS: Catheter placement at the time of lumpectomy was performed in 619 patients (44%), after surgery with ultrasound guidance in 576 patients (41%), and the scar entry technique technique in 197 patients (14%). The type of technique was not associated with age of patient, tumor size, bra size, catheter size, skin spacing, infection, radiation recall, cosmesis, or recurrence. There was a statistically significant increased incidence of premature catheter removals for pathologically related reasons with the open-cavity technique compared with the 2 postoperative methods secondary to final histology reports disqualifying the patient after MammoSite placement. CONCLUSIONS: These registry data show that the MammoSite catheter can be inserted with any 1 of 3 different techniques. A postoperative placement, after the final pathology report is issued, decreases the incidence of premature removal of the catheter because of disqualifying pathology.

Initial clinical experience with the MammoSite breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We present the results of the initial clinical testing of the MammoSite balloon breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. METHODS AND MATERIALS: Seventy patients were enrolled in a multicenter prospective trial testing the applicator for safety and performance. Fifty-four patients were implanted, and 43 patients were ultimately eligible for and received brachytherapy as the sole radiation modality after lumpectomy. Patients were staged T1N0M0 with negative pathologic margins and age >45 years. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using 192Ir high-dose-rate brachytherapy. A minimum skin-to-balloon surface distance of 5 mm was required for treatment. Device performance, complications, and cosmesis were assessed. RESULTS: Computed tomography imaging post-balloon inflation showed 8, 14, and 21 patients with 5-6 mm, 7-9 mm, and >10 mm of skin spacing, respectively. Two patients were explanted because of inadequate skin spacing and 7 because of suboptimal conformance of the surgical cavity to the applicator balloon. One patient was explanted because of positive nodal status and another because of age. The most common side effects related to device placement included mild erythema, drainage, pain, and echymosis. No severe side effects related to implantation, brachytherapy, or explantation occurred. Side effects related to radiation therapy were generally mild with erythema, pain, and dry desquamation being the most common. At 1 month, 88% of patients were evaluated as having good-to-excellent cosmetic results. CONCLUSIONS: The MammoSite balloon breast brachytherapy applicator performed well clinically. All eligible patients completed treatment. Side effects were mild to moderate and self-limiting. Skin-balloon surface distance and balloon-cavity conformance were the main factors limiting the initial use of the device.

Postoperative ultrasound-guided percutaneous placement of a new breast brachytherapy balloon catheter.

BACKGROUND: The optimal technique and timing for the implantation of a recently developed breast brachytherapy balloon catheter (MammoSite; Proxima Therapeutics, Alpharetta, Georgia) have not been well defined. We hypothesized that placing this postoperatively, utilizing percutaneous ultrasound-guided placement, would be preferable. METHODS: Patients who met eligibility requirements for breast brachytherapy were implanted with the MammoSite device utilizing percutaneous ultrasound-guided technique. Additionally, to study optimal timing, a historical cohort of patients operated upon for breast cancer by two of the authors were analyzed to compare the intraoperative and postoperative candidacy for MammoSite placement. RESULTS: Twenty-one of 23 patients successfully completed brachytherapy after implantation, with only 2 (9%) requiring catheter removal secondary to unfavorable balloon positioning. There were no serious complications. Of 343 historical patients with breast cancer, 137 were intraoperative candidates for brachytherapy, but final postoperative histology disqualified 40 (29%). CONCLUSIONS: Implantation of the MammoSite brachytherapy device is optimally performed postoperatively, after the final pathology is defined, utilizing ultrasound-guided percutaneous technique.

Local control, toxicity, and cosmesis in women >70 years enrolled in the American Society of Breast Surgeons accelerated partial breast irradiation registry trial.

PURPOSE: The American Society of Breast Surgeons enrolled women in a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System breast brachytherapy device. The present report examined the outcomes in women aged >70 years enrolled in the trial. METHODS AND MATERIALS: A total of 1,449 primary early stage breast cancers were treated in 1,440 women. Of these, 537 occurred in women >70 years old. Fisher's exact test was performed to correlate age (≤ 70 vs. >70 years) with toxicity and with cosmesis. The association of age with local recurrence (LR) failure times was investigated by fitting a parametric model. RESULTS: Older women were less likely to develop telangiectasias than younger women (7.9% vs. 12.4%, p = 0.0083). The incidence of other toxicities was similar. Cosmesis was good or excellent in 92% of the women >70 years old. No significant difference was found in LR as a function of age. The 5-year actuarial LR rate with invasive disease for the older vs. younger population was 2.79% and 2.92%, respectively (p = 0.5780). In women >70 years with hormone-sensitive tumors ≤ 2 cm who received hormonal therapy (n = 195), the 5-year actuarial rate of LR, overall survival, disease-free survival, and cause-specific survival was 2.06%, 89.3%, 87%, and 97.5%, respectively. These outcomes were similar in women who did not receive hormonal therapy. Women with small, estrogen receptor-negative disease had worse LR, overall survival, and disease-free survival compared with receptor-positive patients. CONCLUSIONS: Accelerated partial breast irradiation with the MammoSite radiation therapy system resulted in low toxicity and produced similar cosmesis and local control at 5 years in women >70 years compared with younger women. This treatment should be considered as an alternative to omitting adjuvant radiotherapy for older women with small-volume, early-stage breast cancer.

A multi-institutional study of feasibility, implementation, and early clinical results with noninvasive breast brachytherapy for tumor bed boost.

PURPOSE: To evaluate the feasibility, implementation, and early results of noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT). METHODS AND MATERIALS: NIBB is a commercially available (AccuBoost, Billerica, MA) mammography-based, brachytherapy system in which the treatment applicators are centered on the planning target volume (PTV) to direct (192)Ir emissions along orthogonal axes. A privacy-encrypted online data registry collected information from 8 independent academic and community-based institutions. Data were from 146 consecutive women with early-stage breast cancer after lumpectomy and WBRT receiving boost with NIBB between July 2007 and March 2010. Toxicity and cosmesis were graded according to the Common Toxicity Criteria (v. 3.0) and the Harvard scale. Median follow-up was 6 months (1-39 months). RESULTS: Grade 1-2 skin toxicity was observed in 64%, 48%, and 21% during the acute (1-3 weeks), intermediate (4-26 weeks), and late-intermediate (>26 weeks) periods. There was no Grade 4 toxicity. At 6 months, for the entire cohort, cosmesis was excellent/good in 62%/38%. The subset receiving NIBB before WBRT had cosmetic scores of 32% and 63%, whereas during WBRT, 58% and 37% were rated as excellent and good, respectively. Breast compression was scored as "uncomfortable" in 12%, 29%, and 59% when NIBB was delivered before, during, or after WBRT. For each patient, the fraction-to-fraction variability in PTV was low. Skin flash was associated with a higher proportion of excellent cosmesis (58% vs. 42%) relative to having the applicator all within breast tissue. CONCLUSIONS: These data indicate that NIBB is feasible and can be consistently implemented in a broad array of practice settings. Preliminary evaluation suggests that NIBB is associated with acceptably mild normal tissue toxicity and favorable early cosmesis. The application of NIBB before WBRT may be associated with better patient tolerance at the expense of less favorable cosmetic outcome.

Dosimetric performance of Strut-Adjusted Volume Implant: a new single-entry multicatheter breast brachytherapy applicator.

PURPOSE: To evaluate the dosimetric performance and clinical utility of the Strut-Adjusted Volume Implant (SAVI) (Cianna Medical, Aliso Viejo, CA) applicator when used as the sole method of radiation therapy for patients with early breast carcinoma. METHODS AND MATERIALS: The dosimetric performance of a Phase II clinical trial has been reported using the SAVI applicator for patients with early breast carcinoma. Cavity volume, planning target volume, dose homogeneity, and dose for organs at risk had been calculated. As a result, the D(90) and D(100) averages had been presented especially on the distances to the skin and the chest wall because these are critical parameters using the MammoSite (Cytyc Corp., Marlborough, MA) technique. RESULTS: D(90) and D(100) averages were 95.8% and 91.2%, respectively. The average dose homogeneity index was 55.9%. Average minimum distances to the skin and chest wall were 15.1 and 23.4mm, respectively. The average D(max) values to the skin and ribs were 249 and 199 cGy/fraction, respectively. The mean V(20) for the lungs was 17.9 cc. The average V(150) and V(200) were 30.80 and 14.91 cc, respectively. CONCLUSIONS: With this study, we have been able to optimize dose distribution to obtain clinically acceptable dose plans, while minimizing doses to healthy tissues. The dose sculpting versatility of SAVI in the clinical setting makes the SAVI applicator a useful addition to the tools available for accelerated partial breast irradiation.

Initial clinical experience with the Strut-Adjusted Volume Implant (SAVI) breast brachytherapy device for accelerated partial-breast irradiation (APBI): first 100 patients with more than 1 year of follow-up.

PURPOSE: The Strut-Adjusted Volume Implant (SAVI; Cianna Medical, Aliso Viejo, CA) is a multichannel single-entry brachytherapy device designed to allow dose modulation to minimize normal tissue dose while simultaneously maximizing target coverage. This is the first report on the initial 102 patients with nearly 2 years of median follow-up. METHODS AND MATERIALS: One hundred two patients were treated at two institutions. Data were collected on eligibility and dosimetry and followed for toxicity and recurrence. RESULTS: The median follow-up is 21 months. Overall dosimetry is outstanding (median percent of target volume receiving 90% of the prescription dose was 95.9%, volume of target receiving 150% of the prescription dose was 27.8 mL, and volume of target receiving 200% of the prescription dose was 14.0 cm(3)). No devices were pulled prior to treatment completion. For patients with a skin bridge of less than 7 mm, the maximum median skin dose was 280 cGy (median percent of target volume receiving 90% of the prescription dose was 95.2%, volume of target receiving 150% of the prescription dose was 25.8 cm(3) and volume of target receiving 200% of the prescription dose was 12.7 mL). For patients with both chest wall and skin of less than 7 mm, the maximum median lung dose was 205 cGy with simultaneous skin dose of 272 cGy. The rate of telangiectasia was 1.9%. Grade 1 hyperpigmentation developed in 10 patients (9.8%) and Grade 2 fibrosis in 2 patients (1.9%). There were 2 symptomatic seromas and 2 cases of asymptomatic fat necrosis (1.9%). Of the patients, 27% were not eligible for MammoSite balloon brachytherapy (Hologic, Inc., Marlborough, MA) and 5% were not eligible for any balloon brachytherapy. The recurrence rate was 1%. CONCLUSIONS: The SAVI appears to safely allow an increase in eligibility for APBI over balloon brachytherapy or three-dimensional conformal radiation, highlighting the outstanding device flexibility to maximize the target dose and minimize the normal tissue dose. The device was well tolerated by patients.

Five-year analysis of treatment efficacy and cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation.

PURPOSE: To present 5-year data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial. METHODS AND MATERIALS: A total of 1440 patients (1449 cases) with early-stage breast cancer receiving breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial-breast irradiation (APBI) (34 Gy in 3.4-Gy fractions). Of 1449 cases, 1255 (87%) had invasive breast cancer (IBC) (median size, 10 mm) and 194 (13%) had ductal carcinoma in situ (DCIS) (median size, 8 mm). Median follow-up was 54 months. RESULTS: Thirty-seven cases (2.6%) developed an ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial rate of 3.80% (3.86% for IBC and 3.39% for DCIS). Negative estrogen receptor status (p=0.0011) was the only clinical, pathologic, or treatment-related variable associated with IBTR for patients with IBC and young age (<50 years; p=0.0096) and positive margin status (p=0.0126) in those with DCIS. The percentage of breasts with good/excellent cosmetic results at 60 months (n=371) was 90.6%. Symptomatic breast seromas were reported in 13.0% of cases, and 2.3% developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 60.5 months, the 5-year actuarial rate of IBTR was 3.04%. CONCLUSION: Treatment efficacy, cosmesis, and toxicity 5 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up.

American Society of Breast Surgeons MammoSite Radiation Therapy System Registry Trial: ductal carcinoma-in-situ subset analysis--4-year data in 194 treated lesions.

BACKGROUND: A subset analysis of the American Society of Breast Surgeons (ASBS) Registry Trial of patients with ductal carcinoma-in-situ (DCIS) was performed to compare results to patients receiving accelerated partial breast irradiation (APBI) for invasive tumors and to results in patients with DCIS receiving whole breast irradiation. METHODS: One hundred ninety-four cases of DCIS were identified from a total of 1,449 cancers treated on the ASBS Registry Trial. Details of the trial are previously published. Analysis of the entire group of cases was performed in regards to toxicity and local control. RESULTS: Median age was 62.1 years with 40.1% and 10.9% younger than 60 years and 50 years, respectively. Nuclear grade distribution was 35.6%, 31.4%, 17%, and 16% high, intermediate, low grade, and unknown, respectively. Necrosis was known to be present 42.3% of cases. Comedo/solid architecture was known to be present in 68% of cases. Median tumor size was 8.0 mm (range .1-45 mm, 15.5% unknown). Median margin was 2 mm; 2 cases had positive margins and 56 cases had less than 1-mm margins. The median follow-up time was 46.7 months. Five isolated ipsilateral breast failures occurred. The actuarial isolated ipsilateral breast failure rate was 2.45% at 4 years. The total in-breast 4-year actuarial failure rate was 3.0%. Three of the patients had a failure elsewhere (1.69% 4-year actuarial rate). Three of the failures were true recurrences (1.33% 4-year actuarial rate). Infection occurred in 16 patients for an 8.2% rate. Seroma formation was reported in 31%, with 13% and 12% symptomatic and requiring intervention, respectively. Seroma formation was statistically higher in open versus closed cases for all seromas. Cosmetic outcome was good to excellent in 90.3% of patients with evaluation at 36 months. CONCLUSIONS: The ASBS Registry Trial includes the largest published collection of DCIS treated with APBI. Four-year follow-up shows result similar to those with invasive cancer treated with APBI, as well as DCIS treated with whole breast irradiation.

Four-year clinical update from the American Society of Breast Surgeons MammoSite brachytherapy trial.

BACKGROUND: We present a 4-year update on the efficacy, cosmetic results, and complications of MammoSite breast brachytherapy in patients enrolled in the American Society of Breast Surgeons registry trial. METHODS: A total of 1,449 breasts in 1,440 patients with early stage breast cancer undergoing breast-conserving therapy were treated with adjuvant, accelerated partial breast irradiation (APBI) (34 Gy in 3.4-Gy fractions) delivered with the MammoSite device. The median follow-up period for the entire group was 36.1 months. RESULTS: The 3-year actuarial rate of ipsilateral breast tumor recurrence was 2.15%. The 3-year actuarial rate of axillary recurrence was .36%. Complication rates were as follows: infection, 9.5%; seroma, 26.8% (symptomatic seroma, 12.7%); and fat necrosis, 2.0%. The percentages of breasts with good or excellent cosmetic results were as follows: 12 months, 95%; 24 months, 94%; 36 months, 94%; and 48 months, 91%. CONCLUSIONS: Locoregional control, complications, and cosmetic outcomes from MammoSite APBI at the 4-year update are acceptable and similar to results seen with other forms of APBI.

Three-year analysis of treatment efficacy, cosmesis, and toxicity by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation (APBI).

BACKGROUND: This report presents 3 years of data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite (Cytyc, Bedford, Mass) Breast Brachytherapy Registry Trial. METHODS: A total of 1440 patients (1449 cases) with early stage breast cancer who were undergoing breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1255 (87%) cases had invasive breast cancer (IBC; median size = 10 mm), and 194 (13%) cases had ductal carcinoma in situ (DCIS; median size = 8 mm). Median follow-up was 30.1 months. RESULTS: Twenty-three (1.6%) cases developed an ipsilateral breast tumor recurrence (IBTR) for a 2-year actuarial rate of 1.04% (1.11% for IBC and 0.59% for DCIS). No variables were associated with IBTR. Six (0.4%) patients developed an axillary failure. The percentages of breasts with good to excellent cosmetic results at 12 (n = 980), 24 (n = 752), 36 (n = 403), and 48 months (n = 67 cases) were 95%, 94%, 93%, and 93%, respectively. Breast seromas were reported in 23.9% of cases (30% in open-cavity implants and 19% in closed-cavity implants). Symptomatic seromas occurred in 10.6% of cases, and 1.5% of cases developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 37.5 months, the 3-year actuarial rate of IBTR was 1.79%. CONCLUSIONS: Treatment efficacy, cosmesis, and toxicity 3 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up.

Timing of Chemotherapy after MammoSite radiation therapy system breast brachytherapy: analysis of the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial.

PURPOSE: To evaluate cosmetic outcome and radiation recall in the American Society of Breast Surgeons registry trial, as a function of the interval between accelerated partial breast irradiation (APBI) and initiation of chemotherapy (CTX). METHODS AND MATERIALS: A total of 1440 patients at 97 institutions participated in this trial. After lumpectomy for early-stage breast cancer, patients received APBI (34 Gy in 10 fractions) with MammoSite RTS brachytherapy. A total of 148 patients received CTX within 90 days of APBI. Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good or fair/poor. RESULTS: Chemotherapy was initiated at a mean of 3.9 weeks after the final MammoSite procedure and was administered 3 weeks after APBI in 94 patients (64%). The early and delayed groups were well balanced with respect to multiple factors that may impact on cosmetic outcome. There was a superior cosmetic outcome in those receiving chemotherapy >3 weeks after APBI (excellent/good in 72.2% at 3 weeks; p = 0.01). Radiation recall in those receiving CTX at 3 weeks (p = 0.09). CONCLUSION: The majority of patients receiving CTX after APBI have excellent/good cosmetic outcomes, with a low rate of radiation recall. Chemotherapy initiated >3 weeks after the final MammoSite procedure seems to be associated with a better cosmetic outcome and lower rate of radiation recall. An excellent/good cosmetic outcome in patients receiving CTX after 3 weeks was similar to the cosmetic outcome of the overall patient population who did not receive CTX.

Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer.

OBJECTIVE: Patients with early-stage invasive ductal breast cancer were prospectively evaluated using MammoSite RTS balloon brachytherapy (RTS Cytyc Corp, Marlborough, MA) as the sole modality for delivering accelerated partial breast irradiation to the lumpectomy bed with breast-conserving surgery. This report presents the 5-year results of the treated patients. METHODS: From May 2000 to October 2001, 70 patients were enrolled in this prospective study. Forty-three patients completed accelerated partial breast irradiation with MammoSite brachytherapy following lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years (mean 65.2 months). Criteria for entry into the study were unifocal invasive ductal carcinoma, tumor size < or = 2 cm, age > or = 45 years, absence of extensive intraductal component, cavity size > or = 3 cm in 1 dimension, node-negative, and final margins negative per National Surgical Adjuvant Breast and Bowel Project definition. A minimum balloon-to-skin surface distance of 5 mm was required. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose-rate brachytherapy. Data on infection, seromas, cosmetic outcome, and toxicities were collected at 3 and 6 months and at yearly intervals. Local recurrences, both true recurrences in the lumpectomy bed and failures outside the initially treated target volume (elsewhere failures), were recorded. Contralateral breast failure rates were noted. RESULTS: The catheter was not implanted in 16 of the 70 enrolled patients due to cavity size not amenable to balloon placement (n = 10), ineligible by criteria (n = 4), and skin spacing (n = 2). Fifty-four patients were implanted and 43 were successfully treated with MammoSite balloon brachytherapy. Reasons for catheter explantation in 11 patients were poor cavity conformance in 7, inadequate skin spacing in 2, positive node in 1 and age less than 45 years in 1. Of the 43 patients who completed treatment, the infection rate was 9.3%. Seroma formation occurred in 32.6% of patients, of which 12% were symptomatic requiring aspiration. Asymptomatic fat necrosis was identified in 4 of the 43 patients, noted from time of catheter removal at 11, 14, 42, and 63 months. Good-excellent cosmetic outcomes were achieved in 83.3% of the 36 patients with more than 5 years of follow-up. Cosmetic outcomes were improved, with increased skin spacing having statistical significance at skin spacing > or = 7 mm. The only serious adverse events were 2 infections: mastitis and abscess. Seven of the 43 treated patients have been discontinued from follow-up. None had a local recurrence recorded at last visit. Reasons for exit from the study were death from metastatic disease (n = 3), lost to follow-up (n = 2), and placed in hospice for other medical conditions (n = 2). No local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. No contralateral cancers have developed. CONCLUSIONS: MammoSite balloon brachytherapy as a sole modality for delivering radiation to the tumor bed has been successful in achieving excellent local control in this initial clinical study of patients with early-stage invasive ductal breast cancer. This has been achieved with minimal toxicities and good-excellent cosmetic outcomes in 83.3%. Accelerated partial breast irradiation using the MammoSite balloon in a carefully selected group of patients has demonstrated 5-year local recurrence results comparable to those achieved with conventional whole breast radiation therapy and interstitial catheter brachytherapy as reported at 5-year data points in studies of these treatment modalities. Poor cavity conformance and inadequate skin distance were the main factors limiting use of the MammoSite device. Extended follow-up will be required to determine the long-term efficacy of this treatment modality.

Initial outcomes for patients treated on the American Society of Breast Surgeons MammoSite clinical trial for ductal carcinoma-in-situ of the breast.

BACKGROUND: The MammoSite device was designed as a breast brachytherapy applicator and is currently used to deliver accelerated partial breast irradiation (APBI). We hypothesized that APBI delivered with the MammoSite device would be well tolerated and be associated with a good cosmetic outcome in patients with ductal carcinoma-in-situ (DCIS). METHODS: From 2002 to 2004, 191 patients with DCIS were enrolled in a registry trial to assess the MammoSite applicator. Fifteen patients were excluded from analysis because of device- or patient-related factors; 7 patients were excluded after receiving a radiotherapy boost, thus leaving 169 patients available for study. Follow-up information was available for 158 patients. The average length of follow-up was 7.35 months. Forty-three patients had at least 1 year of follow-up. RESULTS: Skin spacing for the MammoSite applicator was as follows: < 5 mm, 3 patients (1.78%); 5 to 7 mm, 18 patients (10.65%); and > or = 7 mm, 148 patients (87.57%). Patients with a device-to-skin distance of > or = 7 mm had the best cosmetic result. Patients with a device-to-skin distance of > or = 7 mm also had a lower incidence of radiation dermatitis. Data on 43 patients who were followed up for at least 1 year confirmed these findings. Additional adverse events were primarily related to skin changes, with breast infections occurring in five patients (3.16%). No patient in the study has experienced a recurrence. CONCLUSIONS: APBI delivered via MammoSite is well tolerated in patients with DCIS, and the lowest toxicity was obtained in patients with the greatest device-to-skin distance. Long-term follow-up data regarding patient satisfaction, cosmesis, and efficacy are needed and will be determined from a recently opened large randomized study.