Three-Fraction Accelerated Partial Breast Irradiation (APBI) Delivered With Interstitial Brachytherapy Is Safe: First Results From the Tri-fraction Radiation Therapy Used to Minimize Patient Hospital Trips (TRIUMPH-T) Trial.

PURPOSE: Shorter courses of breast radiotherapy are offered as an alternative to 4 weeks of whole-breast irradiation after lumpectomy, including brachytherapy. A prospective phase 2multi-institution clinical trial to study 3-fraction accelerated partial breast irradiation delivered by brachytherapy was conducted. METHODS AND MATERIALS: The trial treated selected breast cancers after breast-conserving surgery with brachytherapy applicators that delivered 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 2 cm beyond the surgical cavity. Eligible women were age ≥45 years with unicentric invasive or in situ tumors ≤3 cm excised with negative margins and with positive estrogen or progesterone receptors and no metastases to axillary nodes. Strict dosimetric parameters were required to be met and follow up information was collected from the participating sites. RESULTS: Two hundred patients were prospectively enrolled; however, a total of 185 patients who were enrolled were followed for a median of 3.63 years. Three-fraction brachytherapy was associated with low chronic toxicity. There was excellent or good cosmesis in 94% of patients. There were no grade 4 toxicities. Grade 3 fibrosis at the treatment site was present in 1.7% and 32% percent had grades 1 or 2 fibrosis at the treatment site. There was 1 rib fracture. Other late toxicities included 7.4% grade 1 hyperpigmentation, 2% grade 1 telangiectasias, 1.7% symptomatic seromas, 1.7% abscessed cavities, and 1.1% symptomatic fat necrosis. There were 2 (1.1%) ipsilateral local recurrences, 2 (1.1%) nodal recurrences and no distant recurrences. Other incidents included one contralateral breast cancer and 2 second malignancies (lung). CONCLUSIONS: Ultra-short breast brachytherapy is feasible and has excellent toxicity and could be an alternative to standard 5-day, 10 fraction accelerated partial breast irradiation in eligible patients. Patients from this prospective trial will continue to be followed to evaluate long-term outcomes.

Partial breast irradiation: An updated consensus statement from the American brachytherapy society.

PURPOSE: In recent years, results with mature follow-up have been reported for several Phase III trials randomizing women to receive whole breast irradiation (WBI) versus varying modalities of partial breast irradiation (PBI). It is important to recognize that these methods vary in terms of volume of breast tissue treated, dose per fraction, and duration of therapy. As such, clinical and technical guidelines may vary among the various PBI techniques. METHODS: Members of the American Brachytherapy Society with expertise in PBI performed an extensive literature review focusing on the highest quality data available for the numerous PBI options offered in the modern era. Data were evaluated for strength of evidence and published outcomes were assessed. RESULTS: The majority of women enrolled on randomized trials of WBI versus PBI have been age >45 years with tumor size <3 cm, negative margins, and negative lymph nodes. The panel also concluded that PBI can be offered to selected women with estrogen receptor negative and/or Her2 amplified breast cancer, as well as ductal carcinoma in situ, and should generally be avoided in women with extensive lymphovascular space invasion. CONCLUSIONS: This updated guideline summarizes published clinical trials of PBI methods. The panel also highlights the role of PBI for women facing special circumstances, such as history of cosmetic breast augmentation or prior breast irradiation, and discusses promising novel modalities that are currently under study, such as ultrashort and preoperative PBI. Updated consensus guidelines are also provided to inform patient selection for PBI and to characterize the strength of evidence to support varying PBI modalities.

A Three-Dimensional Bioabsorbable Tissue Marker for Volume Replacement and Radiation Planning: A Multicenter Study of Surgical and Patient-Reported Outcomes for 818 Patients with Breast Cancer.

BACKGROUND: Accurate identification of the tumor bed after breast-conserving surgery (BCS) ensures appropriate radiation to the tumor bed while minimizing normal tissue exposure. The BioZorb® three-dimensional (3D) bioabsorbable tissue marker provides a reliable target for radiation therapy (RT) planning and follow-up evaluation while serving as a scaffold to maintain breast contour. METHODS: After informed consent, 818 patients (826 breasts) implanted with the BioZorb® at 14 U.S. sites were enrolled in a national registry. All the patients were prospectively followed with the BioZorb® implant after BCS. The data collected at 3, 6, 12, and 24 months included all demographics, treatment parameters, and provider/patient-assessed cosmesis. RESULTS: The median follow-up period was 18.2 months (range, 0.2-53.4 months). The 30-day breast infection rate was 0.5 % of the patients (n = 4), and re-excision was performed for 8.1 % of the patients (n = 66), whereas 2.6 % of the patients (n = 21) underwent mastectomy. Two patients (0.2 %) had local recurrence. The patient-reported cosmetic outcomes at 6, 12, and 24 months were rated as good-to-excellent by 92.4 %, 90.6 %, and 87.3 % of the patients, respectively and similarly by the surgeons. The radiation oncologists reported planning of target volume (PTV) reduction for 46.2 % of the patients receiving radiation boost, with PTV reduction most commonly estimated at 30 %. CONCLUSIONS: This report describes the first large multicenter study of 818 patients implanted with the BioZorb® tissue marker during BCS. Radiation oncologists found that the device yielded reduced PTVs and that both the patients and the surgeons reported good-to-excellent long-term cosmetic outcomes, with low adverse effects. The BioZorb® 3D tissue marker is a safe adjunct to BCS and may add benefits for both surgeons and radiation oncologists.

Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial.

BACKGROUND: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. METHODS: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. FINDINGS: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. INTERPRETATION: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. FUNDING: National Cancer Institute, US Department of Health and Human Services.

Three-Fraction Accelerated Partial Breast Irradiation (APBI) Delivered With Brachytherapy Applicators Is Feasible and Safe: First Results From the TRIUMPH-T Trial.

PURPOSE: Shorter courses of accelerated partial-breast irradiation delivered as single-fraction intraoperative therapy are now offered as an alternative to 4 to 6 weeks of whole-breast irradiation after lumpectomy. However, this approach has potential shortcomings in patient selection and target volume definition and in dosimetric, radiobiological, and logistical issues. We designed a prospective, phase 2, multi-institution clinical trial to study 2- or 3-day accelerated partial breast irradiation delivered with brachytherapy applicators. METHODS AND MATERIALS: This trial treats select breast cancers after breast-conserving surgery with brachytherapy applicators that deliver 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 1.5 cm beyond the surgical cavity. Eligible women were aged ≥45 years with unicentric invasive or in situ tumors ≤3.0 cm with positive estrogen or progesterone receptors and no metastasis to axillary nodes that have been excised with negative margins. Strict dosimetric parameters were required to be met before acceptance into the trial. RESULTS: A group of 200 patients was prospectively enrolled and followed for a minimum of 6 months. Two- or 3-day brachytherapy was associated with low acute or subacute toxicity, 97.25% excellent or good cosmetic outcomes, and excellent local control in select breast cancers. CONCLUSIONS: Ultrashort breast brachytherapy is dosimetrically feasible and can be delivered with excellent short-term tolerance and low toxicity.

The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation.

PURPOSE: Adjuvant radiation after breast-conserving surgery remains the standard-of-care treatment for patients with ductal carcinoma in situ and early-stage invasive breast cancer. Multiple alternatives to standard whole-breast irradiation exist including accelerated partial-breast irradiation (APBI). Therefore, the purpose of this APBI guideline is to provide updated data for clinicians as well as recommendations regarding appropriate patient selection and techniques to deliver APBI. METHODS: Members of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular created an updated guideline for appropriate patient selection based on an extensive literature search and clinical experience. In addition, data were evaluated with respect to APBI techniques and recommendations presented. RESULTS: Appropriate candidates for APBI include patients aged 45 years or older, all invasive histologies and ductal carcinoma in situ, tumors 3 cm or less, node negative, estrogen receptor positive/negative, no lymphovascular space invasion, and negative margins. With respect to techniques, the strongest evidence is for interstitial brachytherapy and intensity-modulated radiation therapy APBI with moderate evidence to support applicator brachytherapy or three-dimensional conformal radiotherapy APBI. Intraoperative radiation therapy and electronic brachytherapy should not be offered regardless of technique outside of clinical trial. CONCLUSIONS: The updated guidelines presented offer clinicians with a summary of data supporting APBI and guidelines for the appropriate and safe utilization of the technique.

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.

Locoregional recurrence by molecular subtype after multicatheter interstitial accelerated partial breast irradiation: Results from the Pooled Registry Of Multicatheter Interstitial Sites research group.

PURPOSE: To determine in breast tumor recurrence (IBTR) and regional nodal recurrence (RNR) rates for women treated with multicatheter interstitial accelerated partial breast irradiation. METHODS AND MATERIALS: Data from five institutions were collected for patients treated from 1992 to 2013. We report outcomes of 582 breast cancers with ≥1 year of followup. Molecular subtype approximation was performed using estrogen receptor, progesterone receptor, Her2, and grade. The Kaplan-Meier method was used to calculate overall survival, IBTR, RNR, and distant recurrence rates. Univariate and multivariate Cox proportional hazard models were performed to estimate risks of IBTR and RNR. RESULTS: With a median followup time of 5.4 years, the 5-year IBTR rate was 4.7% overall, 3.5% for Luminal A, 4.1% for Luminal B, 5.2% for Luminal Her2, 13.3% for Her2, and 11.3% for triple-negative breast cancer. Positive surgical margins and high grade were associated with increased risk for IBTR, as was Her2 subtype in comparison with Luminal A subtype. Other individual subtypes comparisons did not show a significant difference. Analysis of Luminal A vs. all other subtypes demonstrated lower IBTR risk for Luminal A (5-year IBTR 3.5% vs. 7.3%, p = 0.02). The 5-year RNR rate was 2.1% overall, 0.3% for Luminal A, 4.6% for Luminal B, 2.6% for Luminal Her2, 34.5% for Her2, and 2.3% for triple-negative breast cancer. RNR risk was higher for women with Her2 compared to the other four subtypes and for Luminal B compared to Luminal A subtype. CONCLUSIONS: Molecular subtype influences IBTR and RNR rates in women treated with multicatheter interstitial accelerated partial breast irradiation.

Long-Term Cancer Outcomes From Study NRG Oncology/RTOG 9517: A Phase 2 Study of Accelerated Partial Breast Irradiation With Multicatheter Brachytherapy After Lumpectomy for Early-Stage Breast Cancer.

PURPOSE: To examine 10-year rates of local, regional, and distant recurrences, patterns of recurrence, and survival rates for breast cancer patients enrolled on Study NRG Oncology/Radiation Therapy Oncology Group 9517, a multi-institutional prospective trial that studied one of the earliest methods of accelerated partial breast irradiation (APBI), multicatheter brachytherapy (MCT). METHODS AND MATERIALS: Eligibility included stage I/II unifocal breast cancer <3 cm in size after lumpectomy with negative surgical margins and 0 to 3 positive axillary nodes without extracapsular extension. The APBI dose delivered was 34 Gy in 10 twice-daily fractions over 5 days for high-dose-rate (HDR); and 45 Gy in 3.5 to 5 days for low-dose-rate (LDR) brachytherapy. The primary endpoint was HDR and LDR MCT reproducibility. This analysis focuses on long-term ipsilateral breast recurrence (IBR), contralateral breast cancer events (CBE), regional recurrence (RR), and distant metastases (DM), disease-free, and overall survival. RESULTS: The median follow-up was 12.1 years. One hundred patients were accrued from 1997 to 2000; 98 were evaluable; 65 underwent HDR and 33 LDR MCT. Median age was 62 years; 88% had T1 tumors; 81% were pN0. Seventy-seven percent were estrogen receptor and/or progesterone receptor positive; 33% received adjuvant chemotherapy and 64% antiendocrine therapy. There have been 4 isolated IBRs and 1 IBR with RR, for 5.2% 10-year IBR without DM. There was 1 isolated RR, 1 with IBR, and 1 with a CBE, for 3.1% 10-year RR without DM. The 10-year CBE rate was 4.2%, with 5 total events. Eleven patients have developed DM, 8 have died of breast cancer, and 22 have died from other causes. The 10-year DFS and OS rates are 69.8% and 78.0%, respectively. CONCLUSION: This multi-institutional, phase 2 trial studying MCT-APBI continues to report durable in-breast cancer control rates with long-term follow-up.

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.

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.

Breast conservation therapy without capsular contracture in young augmented women using interstitial brachytherapy.

PURPOSE: To describe a breast-conserving technique using interstitial brachytherapy after lumpectomy and axillary nodal sampling in selected women who are diagnosed with breast cancer in the presence of augmentation mammoplasty. MATERIAL AND METHODS: Over the past 20 years, we have developed and improved a technique of "pinch view" image-guided catheter insertion that avoids implant puncture. Selection criteria include: 1) women of any age with either subpectoral or retroglandular, augmentation implants (silicone or saline) who were diagnosed with stages Tis, T1, T2, N0, or N1 breast cancer; 2) any pathologic subtype of malignant breast cancer was accepted; 3) microscopic tumor extent ≤ 3 cm; 4) axillary node negative or metastasis to 1 to 3 nodes without extracapsular extension; and 5) surgical margins clear by the NSABP "no ink on tumor" definition. More than 250 women have been successfully treated. Patients were treated with high dose rate Iridium-192 brachytherapy to 34 Gy in 10 or 32 Gy in 8 twice daily fractions. The target volume was the surgical cavity edge with 1.5 to 2 cm margin using 3-D treatment planning systems. RESULTS: The implant technique as currently employed is described. There have been no implant ruptures, and the Planning Treatment Volume (PTV-eval) exhibited at least 90% coverage by the 90% isodose line in the vast majority of cases. Dose Homogeneity Index exceeded 70% in most cases. The maximum skin dose was below the prescription dose in every case. Other than some patients with pre-existing capsular contracture, less than 5% experience new capsular contracture after interstitial brachytherapy. CONCLUSIONS: A technique of reliable and reproducible accelerated partial breast irradiation is described that minimizes the risk of capsular contracture by avoiding circumferential dose to the foreign body in the breast.

RTOG 95-17, a Phase II trial to evaluate brachytherapy as the sole method of radiation therapy for Stage I and II breast carcinoma--year-5 toxicity and cosmesis.

PURPOSE: Radiation Therapy Oncology Group (RTOG) 95-17, a Phase II trial to evaluate multicatheter brachytherapy (mCathBrachy) as the sole method of radiation therapy for Stage I-II breast cancer (BrCa), was the first cooperative group trial in North America to evaluate accelerated partial breast irradiation (APBI) and include patient-reported outcomes (PROs). This report presents the year-5 toxicity and cosmesis data. METHODS AND MATERIALS: After lumpectomy and axillary dissection for invasive BrCa (tumor size <3cm with zero to three positive lymph nodes), 100 patients (pts), 98 evaluable, were treated (txed) with mCathBrachy from 1997 to 2000 with 34Gy administered twice daily in 10 high-dose-rate fractions or 45Gy in 3.5-6 days as a low-dose-rate implant to 1-2cm beyond the lumpectomy bed. The PROs and physician-reported outcomes of toxicity, cosmesis, and tx satisfaction at year-5 are reported here, defined as data submitted 54-78 months after tx. RESULTS: Grade (G) 1-2 skin toxicity developed in 78% of the pts and G3 in 13% (no G4). The tx effects included skin dimpling/indentation (37%), fibrosis (45%), telangiectasias (45%), skin catheter marks (54%), and symptomatic fat necrosis (15%). Breast asymmetry was reported in 73%. Rates of excellent-to-good cosmesis were similar between PROs (66%) and radiation oncologists (68%). The PROs of tx satisfaction at year-5 was 75%. CONCLUSIONS: RTOG 95-17 documents the year-5 skin toxicity and tx effects of mCathBrachy APBI, which are associated with PROs of good-to-excellent cosmesis and high tx satisfaction. This emphasizes the importance of PROs when assessing BrCa tx. National Surgical Adjuvant Breast and Bowel Project B39/RTOG 0413 will allow for definitive comparisons between APBI and whole breast radiation therapy.

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.

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.

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.