Strut-based accelerated partial breast irradiation: Report of treatment results for 250 consecutive patients at 5 years from a multicenter retrospective study.

PURPOSE: This registry trial studied the long-term outcomes of women receiving accelerated partial breast irradiation (APBI) using strut-based applicators and reports on the local control, toxicity, and survival for the first 250 patients treated with this device. METHODS AND MATERIALS: Patients were treated using the strut-based brachytherapy device with conventional dose and fractionation of 34 Gy in 10 twice-daily fractions. Planning goals for the planning target volume were V90 > 90%, V150 < 50 cc, and V200 < 20 cc. Toxicity was graded based on the Common Terminology Criteria for Adverse Events v3.0. Recurrence rates were also calculated. RESULTS: Median followup was 59.5 months for the 250 patients. Grade 2 or higher adverse events at any time for hyperpigmentation, induration, erythema, telangiectasia, breast pain, seroma, and fat necrosis were 0.4%, 3.0%, 3.0%, 3.0%, 3.9%, 4.8%, and 1.3%, respectively. The median V90 was 97%, V95 was 95.1%, V150 was 28.7 cc, and V200 was 14.2 cc. For those patients with a less than a 5-mm or 3-mm-skin bridge, the median skin max doses were 272 and 289 cGy, respectively. The 4-year actuarial recurrence rates for true recurrence/marginal miss and ipsilateral breast tumor recurrence were 2.3% and 3.6%, respectively. The 4-year actuarial rates for overall survival, cause-specific survival, and disease-free survival were 97%, 98%, and 92%, respectively. CONCLUSIONS: The strut-based applicator was designed to simplify APBI compared to interstitial brachytherapy. This report confirms excellent tumor control and survival with low toxicity and supports the evidence that brachytherapy has less normal tissue toxicity than APBI with external beam irradiation.

Nomogram for predicting the risk of locoregional recurrence in patients treated with accelerated partial-breast irradiation.

PURPOSE: To develop a nomogram taking into account clinicopathologic features to predict locoregional recurrence (LRR) in patients treated with accelerated partial-breast irradiation (APBI) for early-stage breast cancer. METHODS AND MATERIALS: A total of 2000 breasts (1990 women) were treated with APBI at William Beaumont Hospital (n=551) or on the American Society of Breast Surgeons MammoSite Registry Trial (n=1449). Techniques included multiplanar interstitial catheters (n=98), balloon-based brachytherapy (n=1689), and 3-dimensional conformal radiation therapy (n=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox proportional hazards regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a concordance index. RESULTS: Median follow-up was 5.5 years (range, 0.9-18.3 years). Of the 2000 cases, 435 were excluded because of missing data. Univariate analysis found that age <50 years, pre-/perimenopausal status, close/positive margins, estrogen receptor negativity, and high grade were associated with a higher frequency of LRR. These 5 independent covariates were used to create adjusted estimates, weighting each on a scale of 0-100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR, with a concordance index of 0.641. CONCLUSIONS: The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.

Treatment efficacy with accelerated partial breast irradiation (APBI): final analysis of the American Society of Breast Surgeons MammoSite(®) breast brachytherapy registry trial.

BACKGROUND: The purpose of this study was to examine data on treatment efficacy, cosmesis and toxicities for the final analysis of the American Society of Breast Surgeons MammoSite(®) breast brachytherapy registry trial. METHODS: A total of 1,449 cases of early-stage breast cancer underwent breast conserving therapy. The single-lumen MammoSite(®) device was used to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1,255 cases (87 %) had invasive breast cancer (IBC) and 194 cases had DCIS. Median follow-up was 63.1 months with 45 % of all patients having follow-up of 6 years or longer. RESULTS: There were 41 cases (2.8 %) that developed an ipsilateral breast tumor recurrence (IBTR) for a 5-year actuarial rate of 3.8 % (3.7 % for IBC and 4.1 % for DCIS). Tumor size (odds ratio [OR] = 1.1, p = 0.03) and estrogen receptor negativity (OR = 3.0, p = 0.0009) were associated with IBTR, while a trend was noted for positive margins (OR = 2.0, p = 0.06) and cautionary/unsuitable status compared with suitable status (OR = 1.8, p = 0.07). The percentage of patients with excellent/good cosmetic results at 60, 72, and 84 months was 91.3, 90.5, and 90.6 %, respectively. The overall rates of fat necrosis and infections remained low at 2.5 and 9.6 % with few late toxicity events beyond 2 years. The overall symptomatic seroma rate was 13.4 and 0.6 % beyond 2 years. CONCLUSIONS: The final analysis of treatment efficacy, cosmesis, and toxicity from the American Society of Breast Surgeons MammoSite(®) breast brachytherapy registry trial confirms previously noted excellent results and compares favorably with other forms of APBI with similar follow-up and to outcomes seen in selected patients treated with whole breast irradiation.

Brachytherapy-based partial breast irradiation is associated with low rates of complications and excellent cosmesis.

BACKGROUND: Recent retrospective, claims-based analyses have suggested a potential increased rate of toxicities associated with brachytherapy-based accelerated partial breast irradiation (APBI). The purpose of this analysis was to examine cosmesis and toxicity data from the prospective American Society of Breast Surgeons (ASBS) breast brachytherapy registry trial to compare to the findings from the claims analyses. METHODS: The ASBS breast brachytherapy registry is a prospective nonblinded multi-institutional registry trial. Patients with Stage 0-II breast cancer undergoing breast conserving therapy were eligible. A total of 1665 patients were enrolled and 1449 treated between 2002 and 2004 with a median followup of 63 months. All patients were treated with the MammoSite (Hologic, Inc.) single-lumen device to deliver adjuvant APBI (34Gy in 3.4Gy fractions). RESULTS: The rate of excellent/good cosmesis was 90.6% at 84 months. The rate of a complication (symptomatic seroma, infection, fat necrosis, telangiectasias) at 1 year/any time point was 24.2%/38.5%, whereas the rate of noninfectious complications at 1 year/any time point was 14.8%/28.9%. The rate of symptomatic seroma, fat necrosis, infection, and telangiectasia at any time was 13.4%, 2.5%, 9.6%, and 13.0%, respectively. CONCLUSIONS: The final toxicity analysis from ASBS breast brachytherapy registry trial confirms the previously noted excellent cosmesis and toxicity profiles and fails to confirm retrospective claims analyses that have suggested higher rates of toxicity for brachytherapy-based APBI.

Should ductal carcinoma-in-situ (DCIS) be removed from the ASTRO consensus panel cautionary group for off-protocol use of accelerated partial breast irradiation (APBI)? A pooled analysis of outcomes for 300 patients with DCIS treated with APBI.

PURPOSE: To analyze outcomes in patients with ductal carcinoma-in-situ (DCIS) treated with accelerated partial breast irradiation (APBI) within a pooled set of patients. METHODS: A total of 300 women with DCIS underwent APBI between April 1993 and November 2010 as part of American Society of Breast Surgeons MammoSite Registry Trial (n = 192) or at William Beaumont Hospital (n = 108). Patients with pure DCIS <3 cm (n = 125) were assigned to the cautionary risk group per American Society of Radiation Oncology consensus panel guidelines for off-protocol use of APBI and analyzed compared to a pooled invasive suitable (n = 653) risk group and pooled invasive suitable/cautionary (n = 1,298) risk group. RESULTS: The rate of ipsilateral breast tumor recurrence (IBTR) for all 300 DCIS patients was 2.6 % at 5 years with no regional recurrences, while cause-specific survival was 99.5 % and overall survival (OS) was 96.4 %. When comparing the cautionary DCIS group to the invasive suitable/cautionary group, no difference in IBTR was noted (2.6 vs. 3.1 %, P = 0.90) with significant improvements in distant metastases (0 vs. 2.5 %, P = 0.05), disease-free survival (98.5 vs. 94.4 %, P = 0.05), and OS (95.7 vs. 90.8 %, P = 0.03) noted for DCIS patients. When comparing cautionary DCIS patients to invasive suitable patients, no difference in IBTR were noted (2.6 vs. 2.4 %, P = 0.76), while improved OS for DCIS patients was noted (95.7 vs. 90.9 %, P = 0.02). CONCLUSIONS: This analysis of the largest cohort of patients with DCIS treated with APBI supports previously reported excellent outcomes; as a result of small numbers of events, further data are necessary to confirm these findings.

Impact of margin status on outcomes following accelerated partial breast irradiation using single-lumen balloon-based brachytherapy.

PURPOSE: To examine the impact of margin status on clinical outcomes for patients enrolled in the American Society of Breast Surgeons (ASBrS) MammoSite(®) Registry Trial. METHODS AND MATERIALS: One thousand four hundred forty-nine cases of early-stage breast cancer underwent breast-conserving therapy with a single-lumen balloon-based applicator used to deliver adjuvant accelerated partial breast irradiation (34Gy in 10, bid fractions). One thousand two hundred fifty-five cases (87%) had invasive breast cancer (median size=10mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS; median size=8mm). RESULTS: Patients were stratified by margin status into negative (n=1326), close (<2mm; n=110), and positive (n=13) margins. One hundred twenty-three cases (8.5%) had close or positive margins. Overall, no statistical difference in the 6-year rate of ipsilateral breast tumor recurrence (IBTR) was noted for close margins compared with that of margin-negative patients (8.7% vs. 4.1%, p=0.10) or for positive margins compared with that of margin-negative patients (14.3% vs. 4.1%, p=0.41). In patients with DCIS, there was a statistically significant increase in IBTR with close margins (17.6% vs. 4.2%, p=0.004) and when close and positive margins were pooled (15.7% vs. 4.2%, p=0.01 with a nonsignificant reduction in disease-free survival for DCIS patients with close margins (82.4% vs. 90.8%, p=0.12). The increase in IBTR for close and close/positive patients was secondary to statistically significant increases in elsewhere failures rather than true recurrences/marginal misses. CONCLUSION: Nonsignificant increases in the rates of IBTR were noted with close and positive margins for invasive cancer with further data required to validate these findings.

Evaluation of current consensus statement recommendations for accelerated partial breast irradiation: a pooled analysis of William Beaumont Hospital and American Society of Breast Surgeon MammoSite Registry Trial Data.

PURPOSE: To determine whether the American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) recommendations for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite® Registry Trial. METHODS AND MATERIALS: APBI was used to treat 2127 cases of early-stage breast cancer (WBH, n=678; ASBrS, n=1449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3-dimensional conformal radiation therapy, n=206), whereas all Registry Trial patients received balloon-based brachytherapy. Patients were divided according to the ASTRO CS into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CS group. RESULTS: The median age was 65 years (range, 32-94 years), and the median tumor size was 10.0 mm (range, 0-45 mm). The median follow-up time was 60.6 months. The WBH cohort had more node-positive disease (6.9% vs 2.6%, P<.01) and cautionary patients (49.5% vs 41.8%, P=.06). The 5-year actuarial ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%. The rate of IBTR was not statistically higher between suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (P=.20). The nonsignificant increase in IBTR for the cautionary and unsuitable categories was due to increased elsewhere failures and new primaries (P=.04), not tumor bed recurrence (P=.93). CONCLUSIONS: Excellent outcomes after breast-conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CS guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure in this large patient cohort.

Tumor bed control with balloon-based accelerated partial breast irradiation: incidence of true recurrences versus elsewhere failures in the American Society of Breast Surgery MammoSite(®) Registry Trial.

BACKGROUND: Randomized trials demonstrate that lumpectomy plus whole-breast irradiation (WBI) yields survival equivalent to mastectomy. Studies that use WBI, however, typically report higher tumor bed recurrence rates than elsewhere failures (EF) (historically considered new primary lesions). The rate of true recurrence (TR) versus EF was queried for a large patient cohort treated with accelerated partial breast irradiation (APBI). METHODS: A total of 1,449 cases of early-stage breast cancer were treated on the American Society of Breast Surgeons MammoSite(®) Registry Trial with lumpectomy plus balloon-based APBI (34 Gy, 10 BID fractions). A total of 1,255 cases (87 %) had invasive breast cancer, and 194 patients (13 %) had ductal carcinoma in situ. Rates of TR versus EF were calculated and compared to historical WBI controls. RESULTS: Median follow-up was 60 (range 0-109) months. Fifty patients (3.5 %) developed an ipsilateral breast tumor recurrence (IBTR). The 5-year actuarial rate of IBTR was 3.6 % (invasive breast cancer 3.6 %, ductal carcinoma in situ 3.4 %). Fourteen IBTR (1.1 %) were TR, while 36 (2.6 %) were EF. Estrogen receptor-negative status was associated with IBTR for invasive malignancies as well as for EF only (p < 0.001). Trends for increased rates of EF were noted for increased tumor size (p = 0.067) and extensive intraductal component (p = 0.087). No pathologic factors were explicitly associated with TR. CONCLUSIONS: IBTR after balloon-based APBI is low and similar to rates reported for WBI. In this data set, APBI had fewer tumor bed recurrences (presumably initial cancer recurrences) than EF (presumably new primary lesions). This suggests that balloon-based APBI has a tumor bed control rate that is at least equal to (and potentially higher than) WBI.

Comparison of survival and regional failure between accelerated partial breast irradiation and whole breast irradiation.

PURPOSE: To compare rates of regional recurrence (RR) and overall survival (OS) between a pooled set of 1400 patients treated on the American Society of Breast Surgeons MammoSite (Hologic, Inc., Bedford, MA) Registry Trial to a cohort of 3600 patients treated with whole breast irradiation (WBI). METHODS AND MATERIALS: A total of 1440 women underwent accelerated partial breast irradiation (APBI) between 2002 and 2004 as part of the American Society of Breast Surgeons Registry Trial and a total of 3593 patients who received WBI were evaluated from the Surveillance Epidemiology and End Results database with treatment received between 1980 and 2009. A matched-pair analysis was performed based on age, receipt of hormonal therapy, chemotherapy, nodal status, and tumor size (1051 patients per arm). Rates of RR and OS were then analyzed for each group. RESULTS: After the match, no differences in patient characteristics were noted when tumor size was evaluated as a continuous variable. Rates of RR and OS were similar between the WBI and APBI groups. A Cox regression model found no difference between WBI and APBI with regard to RR; however, OS was improved in the APBI cohort (hazard ratio 0.008, p<0.0001). CONCLUSIONS: With one of the largest patient populations to date comparing WBI and APBI, no difference in RR or OS was noted between WBI and APBI treatment. Until the publication of prospective Phase III trials, these data support the continued use of APBI on protocol and off protocol in appropriately selected patients.

Bioelectrical impedance for detecting and monitoring patients for the development of upper limb lymphedema in the clinic.

BACKGROUND: Single-frequency bioelectrical impedance (BI) has been used to measure extracellular fluid in the upper limbs. The purpose of the study was to evaluate BI's ability to detect and monitor upper limb changes in based upon the extent of various treatments and to assess its practicality. METHODS: Patients with newly diagnosed breast cancer were evaluated at baseline and after procedures that could potentially affect fluid accumulation in the arm and signal the possible development of early lymphedema. The magnitude of the change in lymphedema index ratios (LIR) from these procedures was evaluated to determine the sensitivity of BI. RESULTS: A total of 64 patients were evaluated. Although no difference in LIRs was noted by the extent of surgical procedure (lumpectomy 2.1 vs. mastectomy 1.1; P = .49), a trend was noted for increased LIRs with more aggressive axillary staging when sentinel lymph node was compared with axillary lymph node dissection (1.3 vs. 3.4; P = .08). A trend for an increased LIR with more aggressive local therapy also was noted when using a cutoff of less than 4 lymph nodes sampled compared with 4 or more nodes sampled (1.2 vs. 2.6; P = .09). CONCLUSIONS: In this limited analysis, L-Dex readings paralleled the extent of surgical interventions and suggest that they can be used to monitor patients for the early onset of edema. Further studies are needed to help validate the extent, degree, and chronologic time frame of these changes to help define recommendations for closer monitoring of patients and possible early intervention.

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.

Predictors of local recurrence following accelerated partial breast irradiation: a pooled analysis.

PURPOSE: To analyze a pooled set of nearly 2,000 patients treated on the American Society of Breast Surgeons (ASBS) Mammosite Registry Trial and at William Beaumont Hospital (WBH) to identify factors associated with local recurrence following accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 1,961 women underwent partial breast irradiation between April 1993 and November 2010 as part of the ASBS Registry Trial or at WBH. Rates of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed for each group and for the pooled cohort. Clinical, pathologic, and treatment-related variables were analyzed including age, tumor stage/size, estrogen receptor status, surgical margins, and lymph node status to determine their association with IBTR. RESULTS: The two groups weres similar, but WBH patients were more frequently node positive, had positive margins, and were less likely to be within the American Society for Radiation Oncology-unsuitable group. At 5 years, the rates of IBTR, RR, DM, DFS, CSS, and OS for the pooled group of patients were 2.9%, 0.5%, 2.4%, 89.1%, 98.5%, and 91.8%, respectively. The 5-year rate of true recurrence/marginal miss was 0.8%. Univariate analysis of IBTR found that negative estrogen receptor status (odds ratio [OR], 2.83, 95% confidence interval 1.55-5.13, p = 0.0007) was the only factor significantly associated with IBTR, while a trend was seen for age less than 50 (OR 1.80, 95% confidence interval 0.90-3.58, p = 0.10). CONCLUSIONS: Excellent 5-year outcomes were seen following APBI in over 1,900 patients. Estrogen receptor negativity was the only factor associated with IBTR, while a trend for age less than 50 was noted. Significant differences in factors associated with IBTR were noted between cohorts, suggesting that factors driving IBTR may be predicated based on the risk stratification of the patients being treated.

Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation.

BACKGROUND: The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) using accelerated partial breast irradiation (APBI). METHODS: In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4-Gy fractions). One thousand two hundred fifty-five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow-up was 60 months. RESULTS: Fifty patients (3.5%) developed an IBTR for a 5-year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 recurrences with known histology, 78% were IBC, and 22% were DCIS. After IBTR, 28 of 38 patients (74%) underwent salvage mastectomy, and 9 of 38 patients (26%) had a second attempt at BCT. Adjuvant therapies included tamoxifen in 8 patients (16%) and systemic chemotherapy in 6 patients (12%). The 3-year rates of disease-free survival, cause-specific survival, and overall survival after IBTR were 58.7%, 92.1%, and 80.5%, respectively. CONCLUSIONS: With 5 years of follow-up, APBI produced clinical outcomes and patterns of failure comparable to those achieved with whole breast irradiation. Patients who developed an IBTR after APBI had excellent 3-year survival outcomes after salvage treatments.

Factors associated with chest wall toxicity after accelerated partial breast irradiation using high-dose-rate brachytherapy.

PURPOSE: The purpose of this analysis was to evaluate dose-volume relationships associated with a higher probability for developing chest wall toxicity (pain) after accelerated partial breast irradiation (APBI) by using both single-lumen and multilumen brachytherapy. METHODS AND MATERIALS: Rib dose data were available for 89 patients treated with APBI and were correlated with the development of chest wall/rib pain at any point after treatment. Ribs were contoured on computed tomography planning scans, and rib dose-volume histograms (DVH) along with histograms for other structures were constructed. Rib DVH data for all patients were sampled at all volumes ≥0.008 cubic centimeter (cc) (for maximum dose related to pain) and at volumes of 0.5, 1, 2, and 3 cc for analysis. Rib pain was evaluated at each follow-up visit. Patient responses were marked as yes or no. No attempt was made to grade responses. Eighty-nine responses were available for this analysis. RESULTS: Nineteen patients (21.3%) complained of transient chest wall/rib pain at any point in follow-up. Analysis showed a direct correlation between total dose received and volume of rib irradiated with the probability of developing rib/chest wall pain at any point after follow-up. The median maximum dose at volumes ≥0.008 cc of rib in patients who experienced chest wall pain was 132% of the prescribed dose versus 95% of the prescribed dose in those patients who did not experience pain (p = 0.0035). CONCLUSIONS: Although the incidence of chest wall/rib pain is quite low with APBI brachytherapy, attempts should be made to keep the volume of rib irradiated at a minimum and the maximum dose received by the chest wall as low as reasonably achievable.

Factors associated with optimal long-term cosmetic results in patients treated with accelerated partial breast irradiation using balloon-based brachytherapy.

PURPOSE: To evaluate factors associated with optimal cosmetic results at 72 months for early-stage breast cancer patients treated with Mammosite balloon-based accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 1,440 patients (1,449 cases) with early-stage breast cancer undergoing breast-conserving therapy were treated with balloon-based brachytherapy to deliver APBI (34 Gy in 3.4-Gy fractions). Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good (E/G) or fair/poor (F/P). Follow-up was evaluated at 36 and 72 months to establish long-term cosmesis, stability of cosmesis, and factors associated with optimal results. RESULTS: The percentage of evaluable patients with excellent/good (E/G) cosmetic results at 36 months and more than 72 months were 93.3% (n = 708/759) and 90.4% (n = 235/260). Factors associated with optimal cosmetic results at 72 months included: larger skin spacing (p = 0.04) and T1 tumors (p = 0.02). Using multiple regression analysis, the only factors predictive of worse cosmetic outcome at 72 months were smaller skin spacing (odds ratio [OR], 0.89; confidence interval [CI], 0.80-0.99) and tumors greater than 2 cm (OR, 4.96, CI, 1.53-16.07). In all, 227 patients had both a 36-month and a 72-month cosmetic evaluation. The number of patients with E/G cosmetic results decreased only slightly from 93.4% at 3 years to 90.8% (p = 0.13) at 6 years, respectively. CONCLUSIONS: APBI delivered with balloon-based brachytherapy produced E/G cosmetic results in 90.4% of cases at 6 years. Larger tumors (T2) and smaller skin spacing were found to be the two most important independent predictors of cosmesis.

Six-year analysis of treatment-related toxicities in patients treated with accelerated partial breast irradiation on the American Society of Breast Surgeons MammoSite Breast Brachytherapy registry trial.

BACKGROUND: The American Society of Breast Surgeons (ASBrS) enrolled women in a registry trial to prospectively study patients treated with the MammoSite RTS device. This report presents 6-year data on treatment-related toxicities from the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated with accelerated partial breast irradiation (APBI) using the MammoSite device (34 Gy in 10 fractions) in 1440 women. Of these, 1255 case (87%) had invasive breast cancer (IBC) (median size = 10 mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS) (median size = 8 mm). Median follow-up was 59 months. Fisher exact test was performed to correlate categorical covariates with toxicity. RESULTS: Breast seromas were reported in 28% of cases (35.5% with open cavity and 21.7% with closed cavity placement). Also, 13% of all treated breasts developed symptomatic seromas, and 77% of these seromas developed during the 1st year after treatment. There were 172 cases (11.9%) that required drainage to correct. Use of chemotherapy and balloon fill >50 cc were associated with the development of symptomatic seromas. Also, 2.3% of patients developed fat necrosis (FN). The incidence of FN during years 1 and 2 were 0.9% and 0.8%, respectively. Seroma formation, use of hormonal therapy, breast infection, and A/B cup size were associated with fat necrosis. There were 138 infections (9.5%) recorded; 98% occurred during the 1st year after treatment. Chemotherapy and seroma formation were associated with the development of infections. CONCLUSIONS: Treatment-related toxicities 6 years after treatment with APBI using the MammoSite device are similar to those reported with other forms of APBI with similar follow-up.

Axillary failure in patients treated with MammoSite accelerated partial breast irradiation.

BACKGROUND: The risk of axillary failure (AF) after accelerated partial breast irradiation (APBI) using MammoSite brachytherapy is unknown and has been source of concern as the axillary region is not treated with this technique. We aimed to determine the rate of AF in patients treated with APBI and identify factors associated with its occurrence. METHODS: Data from the American Society of Breast Surgeons MammoSite Registry Trial were reviewed and patients with AF were identified. Clinical, pathologic and treatment-related variables were analyzed to determine which factors were associated with AF. RESULTS: A total of 1440 patients underwent MammoSite APBI. A total of 1449 cases were treated (9 patients received bilateral treatment), 1255 cases (87%) of invasive breast cancer and 194 cases (13%) of ductal carcinoma in situ (DCIS). The median length of follow-up was 59 months. There were 10 patients who had an AF. Of these, 9 patients had an initial diagnosis of invasive cancer and 1 had an initial diagnosis of DCIS. The 5-year actuarial rate of AF was 0.79%. The only independent risk factor for AF identified by multivariate analysis was the presence of high-grade disease (P=.008). The 5-year overall survival rate in patients with an AF was 77.8% (there was 1 death related to breast cancer). CONCLUSIONS: The rate of AF after MammoSite APBI is low and appears to be similar to that achieved with whole-breast irradiation.

Ductal carcinoma in situ treated with breast-conserving surgery and accelerated partial breast irradiation: comparison of the Mammosite registry trial with intergroup study E5194.

BACKGROUND: The purpose of this study was to determine the ipsilateral breast tumor recurrence (IBTR) in ductal carcinoma in situ (DCIS) patients treated in the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial who met the criteria for E5194 treated with local excision and adjuvant accelerated partial breast irradiation (APBI). METHODS: A total of 194 patients with DCIS were treated between 2002 and 2004 in the Mammosite registry trial; of these, 70 patients met the enrollment criteria for E5194: 1) low to intermediate grade (LIG)-pathological size >0.3 but <2.5 cm and margins ≥3 mm (n = 41) or 2) high grade (HG)-pathological size <1 cm and margins ≥3 mm (n = 29). All patients were treated with lumpectomy followed by adjuvant APBI using MammoSite. Median follow-up was 52.7 months (range, 0-88.4). SAS (version 8.2) was used for statistical analysis. RESULTS: In the LIG cohort, the 5-year IBTR was 0%, compared with 6.1% at 5 years in E5194. In the HG cohort, the 5-year IBTR was 5.3%, compared with 15.3% at 5 years in E5194. The overall 5-year IBTR was 2%, and there were no cases of elsewhere or regional failures in the entire cohort. The 5-year contralateral breast event rate was 0% and 5.6% in LIG and HG patients, respectively (compared with 3.5% and 4.2%, respectively, in E5194). CONCLUSIONS: This study found that patients who met the criteria of E5194 treated with APBI had extremely low rates of recurrence (0% vs 6.1% in the LIG cohort and 5.3% vs 15.3% in the HG cohort).

Accurate verification of balloon rotation correction for the Contura multilumen device for accelerated partial breast irradiation.

PURPOSE: To validate a method of accurately confirming the orientation of the Contura multilumen balloon catheter before each fraction and to determine if any residual device rotation remains after adjustment. METHODS AND MATERIALS: Sixteen patients underwent CT scans before each treatment with accelerated partial breast irradiation. Before acquisition of CT scans for planning, each patient had a skin mark drawn to align with Lumen #1 (the Contura [SenoRx, Inc., Irvine, CA] has a black line on the shaft of the applicator to identify this lumen). In addition, a CT spot marker was used as a fixed reference point on the patient's skin. CT markers (used for lumen identification and reconstruction) were also used as additional reference points for distance measurements. The distances measured from the CT spot marker to the three reproducible points on the CT markers were used for balloon rotation verification. These measurements were performed for each daily fraction on reproducible CT axial views. RESULTS: Three hundred eighteen measurements were obtained. Median residual rotation for all cases was 0.2mm (standard deviation=0.797). Later fractions and skin spacing changes over time were associated with slightly greater residual rotation (Fraction #1 vs. Fraction #10, 0.1 vs. 0.3mm, p=0.05; and skin spacing change ≤2 vs. >2mm, 0.2 vs. 0.5mm, p=0.0019, respectively). CONCLUSIONS: These results confirm external alignment of a skin mark with Lumen #1 (on the Contura catheter) is an accurate and reliable method to align the balloon before treatment and that no significant internal device rotation (0.2mm) is likely to occur.

Optimal application of the Contura multilumen balloon breast brachytherapy catheter vacuum port to deliver accelerated partial breast irradiation.

PURPOSE: The impact of using the Contura multilumen balloon (MLB) (SenoRx, Inc., Irvine, CA) breast brachytherapy catheter's vacuum port in patients treated with accelerated partial breast irradiation (APBI) was analyzed. METHODS AND MATERIALS: Data from 32 patients at two sites were reviewed. Variables analyzed included the seroma fluid (SF):air volume around the MLB before and after vacuum port use and on its ability to improve (1) the eligibility of patients for APBI and (2) dose coverage of the planning target volume for evaluation (PTV_EVAL) in eligible patients. RESULTS: The median SF/air volume before vacuum removal was 6.8 cc vs. 0.8 cc after vacuum removal (median reduction in SF/air volume was 90.5%). Before vacuum port use, the median SF/air volume expressed as percentage of the PTV_EVAL was 7.8% (range, 1.9-26.6) in all patients. After application of the vacuum, this was reduced to 1.2%. Before vacuum port use, 10 (31.3%) patients were not considered acceptable candidates for APBI because the SF/air volume:PTV_EVAL ratio (SF:PTV) was greater than 10% (range, 10.1-26.6%; median, 15.2%). After vacuum port use, the median SF:PTV ratio was 1.6% for a median reduction of 91.5%. In addition, the percentage of the prescribed dose covering greater than or equal to 90% of the PTV_EVAL proportionally increased a median of 8% (range, 3-10%) in eligible patients. CONCLUSION: Use of the Contura MLB vacuum port significantly improved the conformity of the target tissue to the balloon surface, leading to reproducible dose delivery and increased target volume coverage. In addition, application of the vacuum allowed the safe treatment of unacceptable patients with APBI.