Cost-Effectiveness Analysis of Ultra-Hypofractionated Whole Breast Radiation Therapy Alone Versus Hormone Therapy Alone or Combined Treatment for Low-Risk ER-Positive Early Stage Breast Cancer in Women Aged 65 Years and Older.

PURPOSE: The optimal management of early-stage, low-risk, hormone-positive breast cancer in older women remains controversial. Recent trials have shown that 5-fraction ultrahypofractionated whole-breast irradiation (U-WBI) has similar outcomes to longer courses, reducing the cost and inconvenience of treatment. We performed a cost-utility analysis to compare U-WBI to hormone therapy alone or their combination. METHODS AND MATERIALS: We simulated 3 different treatment approaches for women age 65 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were U-WBI performed with a 3-dimensional conformal technique over 5 fractions without a boost ("radiation therapy [RT] alone"), adjuvant hormone therapy (anastrozole for 5 years) without RT ("aromatase-inhibitor [AI] alone"), or the combination of the 2. The combination strategy was calibrated to match trial results, and the relative effectiveness of the RT alone and AI alone strategies were inferred from previous randomized trials. The primary endpoint was the cost-effectiveness of the 3 strategies over a lifetime horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/quality-adjusted life-year deemed "cost-effective." RESULTS: The model results compared with the prespecified target outcomes. On average, RT alone was the least expensive strategy ($14,775), with AI alone slightly more ($14,998), and combination therapy the costliest ($19,802). RT alone dominated AI alone (the incremental cost-effectiveness ratio [ICER] -$5089). Combination therapy, compared with RT alone, was slightly more expensive than our definition of cost-effective (ICER $113,468) but was cost-effective compared with AI alone (ICER $54,451). Probabilistic sensitivity analysis demonstrated RT alone to be cost-effective in 50% of trials, with combination therapy in 36% and AI alone in 14%. CONCLUSIONS: U-WBI alone appears the more cost-effective de-escalation strategy for these low-risk patients, compared with AI alone. Combining U-WBI and AI appears more costly but may be preferred by some patients.

Cost-Effectiveness Analysis of No Adjuvant Therapy Versus Partial Breast Irradiation Alone Versus Combined Treatment for Treatment of Low-Risk DCIS: A Microsimulation.

PURPOSE: Adjuvant therapy in patients with ductal carcinoma in situ who undergo partial mastectomy remains controversial, particularly for low-risk patients (60 years or older, estrogen-positive, tumor extent < 2.5 cm, grade 1 or 2, and margins ≥ 3 mm). We performed a cost-effectiveness analysis comparing three strategies: no adjuvant treatment after surgery, a five-fraction course of accelerated partial breast irradiation using intensity-modulated radiation therapy (accelerated partial breast irradiation [APBI]-alone), or APBI plus an aromatase inhibitor for 5 years. MATERIALS AND METHODS: Outcomes including local recurrence, distant metastases, and survival as well as toxicity data were modeled by a patient-level Markov microsimulation model, which were validated against trial data. Costs of treatment and possible adverse events were included from the societal perspective over a lifetime horizon, adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALYs) were calculated based on utilities extracted from the literature. RESULTS: No adjuvant therapy was the least costly approach ($5,744), followed by APBI-alone ($11,070); combined therapy was costliest ($16,052). Adjuvant therapy resulted in slightly higher QALYs (no adjuvant, 11.320; APBI-alone, 11.343; and combination, 11.381). In the base case, no treatment was the cost-effective strategy, with an incremental cost-effectiveness ratio of $239,109/QALY for APBI-alone and $171,718/QALY for combined therapy. The incremental cost-effectiveness ratio for combined therapy compared with APBI-alone was $131,949. Probabilistic sensitivity analyses found that no therapy was cost effective (defined as $100,000/QALY of lower) in 63% of trials, APBI-alone in 19%, and the combination in 18%. CONCLUSION: No adjuvant therapy represents the most cost-effective approach for postmenopausal women 60 years or older who receive partial mastectomy for low-risk ductal carcinoma in situ.

Ultra-Short Fraction Schedules as Part of De-intensification Strategies for Early-Stage Breast Cancer.

Adjuvant radiation therapy (RT) following breast-conserving surgery (BCS) represents a standard approach for most patients treated with breast-conserving therapy (BCT) for early-stage breast cancer. The first-generation of adjuvant RT schedules delivered daily treatment to the whole breast over 5-7 weeks. Although efficacious, this presented patients with a protracted course of treatment, reducing compliance and quality of life. While hypofractionated whole-breast irradiation (WBI) has become the standard, and part of the second-generation of RT regimens, it still requires 3-4 weeks. Concurrently, partial-breast irradiation (PBI) has also been explored as a technique to complete RT in a much shorter time period (1-3 weeks). There are now seven trials confirming the efficacy of this shorter treatment approach compared with standard WBI. In an effort to further reduce treatment duration, ultra-short WBI and PBI regimens have recently emerged as the third-generation of breast radiation schedules, allowing for the completion of treatment in 5 days or less. With respect to WBI, recent data from the FAST-Forward trial (which evaluated five fractions of WBI delivered in 1 week) demonstrated no difference in clinical outcomes at 5 years, with limited difference in toxicity, compared with hypofractionated 3-week WBI. Regarding PBI, published data on five-fraction regimens delivered in 2 weeks have also demonstrated comparable outcomes at 10 years, with reduced toxicities with long-term follow-up. This report will review additional ongoing studies evaluating even shorter courses of adjuvant RT treatment (one to five fractions), including single-fraction PBI or WBI.

Outcomes with Partial Breast Irradiation vs. Whole Breast Irradiation: a Meta-Analysis.

BACKGROUND: Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques. METHODS: A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI. RESULTS: A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68-3.2%) and WBI (1.7%, 95% HPD 0.92-2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI. CONCLUSIONS: IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques.

Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older.

PURPOSE: We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination. METHODS: We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature. RESULTS: The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years. CONCLUSIONS: Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.

Radiation Therapy Without Hormone Therapy for Women Age 70 or Above with Low-Risk Early Breast Cancer: A Microsimulation.

PURPOSE: Hormone therapy without radiation therapy is considered appropriate for women age 70 or above with low-risk, hormone-positive breast cancer after partial mastectomy. However, some patients may prefer radiation without hormone therapy, for which there is minimal modern data. We modeled the comparative efficacy of aromatase inhibition alone without radiation versus radiation alone without hormone therapy. METHODS AND MATERIALS: We constructed a patient-level Markov model and compared 5 years of anastrozole to a 15-fraction course of radiation without boost or anastrozole. The relative effectiveness between treatments was based on the National Surgical Adjuvant Breast and Bowel Project B-21 trial, which was further adjusted such that the endocrine-alone arm matched the Cancer and Leukemia Group B 9343 and PRIME II trials. Common or severe side effects were considered. Eight survival metrics were assessed and validated against clinical trial data. The cost-efficacy of each strategy was considered using the quality-adjusted life year and incremental cost-effectiveness ratio (ICER). RESULTS: The model's predicted outcomes matched those demonstrated by modern trials. Aromatase inhibitors were superior in preventing contralateral cancers, with a small impact on the risk of distant metastatic disease. Radiation was superior in preventing ipsilateral breast tumor recurrence with a small impact on regional failure. No clinically significant differences were seen in the other 4 oncologic endpoints. Differences in quality-adjusted life years were small, but radiation therapy was $3809 more expensive over the average lifetime. The ICER suggested anastrozole was cost-effective in 62% of probabilistic simulations. However, the ICER was unstable owing to a denominator that approached zero. CONCLUSIONS: Women age 70 or above with low-risk early breast cancer who are reluctant or unable to pursue adjuvant aromatase inhibition can safely pursue adjuvant radiation alone with limited differences in outcome and a modest increase in costs.

Does an Algorithmic Approach to Using Brachytherapy and External Beam Radiation Result in Good Function, Local Control Rates, and Low Morbidity in Patients With Extremity Soft Tissue Sarcoma?

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) and external-beam radiation therapy (EBRT) are two modalities used in the treatment of soft tissue sarcoma. Previous work at our institution showed early complications and outcomes for patients treated with HDR-BT, EBRT, or a combination of both radiation therapy modalities. As the general indications for each of these approaches to radiation therapy differ, it is important to evaluate the use of each in an algorithmic way, reflecting how they are used in contemporary practice at sites that use these treatments. QUESTION/PURPOSES: (1) To determine the proportions of intermediate- and long-term complications associated with the use of brachytherapy in the treatment of primary high-grade extremity soft tissue sarcomas; (2), to characterize the long-term morbidity of the three radiation treatment groups using the Radiation Therapy Oncology Group/ European Organization for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Scoring Scheme; (3) to determine whether treatment with HDR-BT, EBRT, and HDR-BT+EBRT therapy, in combination with limb-salvage surgery, results in acceptable local control in this high-risk group of sarcomas. METHODS: We retrospectively studied data from 171 patients with a diagnosis of high-grade extremity soft tissue sarcoma treated with limb-sparing surgery and radiation therapy between 1990 and 2012 at our institution, with a mean followup of 72 months. Of the 171 patients, 33 (20%) were treated with HDR-BT, 128 (75%) with EBRT, and 10 (6%) with HDR-BT+EBRT. We excluded 265 patients with soft tissue sarcomas owing to axial tumor location, previous radiation to the affected extremity, incomplete patient records, patients receiving primary amputation, recurrent tumors, pediatric patients, low- and intermediate-grade tumors, and rhabdoid histology. Fifteen patients (9%) were lost to followup for any reason including died of disease or other causes during the first 12 months postoperatively. This included four patients who received HDR-BT (12%), 11 who received EBRT (9%), and none who received HDR-BT+EBRT (0%) with less than 12 months followup. Determination of radiation therapy technique for each patient was individualized in a multidisciplinary forum of sarcoma specialists. Anticipated close or positive surgical margins and a low likelihood of complex soft tissue procedures were factors that encouraged use of brachytherapy, whereas the anticipated need for secondary procedures and/or soft tissue coverage encouraged use of EBRT alone. Combination therapy was used when the treatment volume exceeded the treatment field of the brachytherapy catheters or when the catheters were used to boost a close or positive surgical margin. Local recurrence, complications, and morbidity outcomes scores (RTOG) were calculated based on chart review. Between-group comparisons pertaining to the proportion of patients experiencing complications, morbidity outcomes scores, and local recurrence rates were not performed because of dissimilarities among the patients in each group at baseline. RESULTS: The HDR-BT treatment group showed a high incidence of intermediate-term complications, with the three most common being: deep infection (33%, 11 of 33); dehiscence and delayed wound healing (24%, eight of 33); and seroma and hematoma (21%, seven of 33). The EBRT group showed a high incidence of intermediate- and long-term complications with the three most common being: chronic radiation dermatitis (35%, 45 of 128); fibrosis (27%, 35 of 128); and chronic pain and neuritis (13%, 16 of 128). The RTOG scores for each treatment group were: HDR-BT 0.8 ± SD 1.2; EBRT 1.9 ± 2.0; and HDR-BT+EBRT 1.7 ± 1.7. Overall, 142 of 169 (84%) patients were free from local recurrence: 27 (82%) in the HDR-BT group, 108 (86%) in the EBRT group, and seven (70%) in the combination therapy group. CONCLUSIONS: In this single-institution study, an algorithmic approach to using HDR-BT and EBRT in the treatment of patients with high-grade soft tissue sarcomas can yield acceptable complication rates, good morbidity outcome scores, and a high degree of local control. Based on these results, we believe HDR-BT is best for patients with an anticipated close margin, a positive surgical margin, and for patients who are unlikely to receive a complex soft tissue procedure. Conversely, if a secondary procedure and/or soft tissue coverage are likely to be used, EBRT alone may be reasonable. Finally, combination therapy might be considered when the treatment volume exceeded the treatment field capacity for HDR-BT or when the catheters were used to boost a close or positive surgical margin. LEVEL OF EVIDENCE: Level IV, therapeutic study.

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.

Skin surface brachytherapy: A survey of contemporary practice patterns.

PURPOSE: The aim of this study was to define current patterns of care among radiation oncologists who use skin surface brachytherapy for the treatment of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) in academic and community settings. METHODS AND MATERIALS: A 30-question electronic survey was administered to clinician members of the American Brachytherapy Society. The respondents were asked to provide details regarding their clinical practice and their approach to skin surface brachytherapy. RESULTS: A total of 16 surveys were returned. Among the respondents, aggregate experience varied from 8 to 1800 cases. Most preferred brachytherapy over external beam radiation because of shorter treatment course, conformality of treatment for irregular or curved targets, and shallow dose deposition. Of the total, 60% of respondents routinely estimated lesion depth via ultrasound before initiating treatment. Treatment margin on gross disease varied widely (range, 3-15 mm; median, 5 mm). Hypofractionation was the preferred dose schedule. Prescribed doses ranged from 30 Gy in five fractions to 64 Gy in 32 fractions (EQD2, 40 Gy-65 Gy). There was a tendency to increase the number of fractions for larger targets, although some used the same fractionation regardless of anatomic location or lesion size. There was no consensus on dosimetric constraints, and some respondents reported cases of severe toxicity, particularly when treating the pretibial skin. CONCLUSIONS: This pattern of care study suggests that skin brachytherapy can be a convenient and safe tool for treatment of BCC and cSCC. Prospective trials and the development of expert consensus guidelines would be beneficial for optimizing skin surface brachytherapy and reducing practice variation.

Accelerated partial breast irradiation: An update on published Level I evidence.

Multiple adjuvant radiation therapy options currently exist for women following breast-conserving surgery including standard fractionated whole breast irradiation (WBI), accelerated whole breast irradiation (AWBI), and accelerated partial breast irradiation (APBI). The recent publication of several randomized trials comparing APBI to standard WBI provides Level I evidence supporting APBI. The purpose of this review is to summarize the Level I data supporting APBI in an effort to provide guidance when to offer this treatment approach vs. standard WBI, AWBI, or excision alone and to address questions related to its application. Four contemporary trials with over 2000 patients comparing APBI and WBI have been published and demonstrate no differences in the rates of local/regional recurrence or survival though long-term followup is limited to one study. In addition, reductions in the rates of acute and chronic toxicity and improvements in cosmetic outcome were noted in two of these trials (the University of Florence and the Hungarian Phase III trials, respectively). When contrasting other treatment approaches to APBI, patients treated in studies using AWBI have many comparable clinical and pathologic characteristics, whereas studies investigating endocrine therapy alone (surgery with no adjuvant radiation therapy) have much "lower risk" patients based on clinical, pathologic, and treatment-related criteria. Although significant Level I evidence now exists supporting the use of APBI as an alternative to WBI in selected patients undergoing breast-conserving therapy, additional data are needed to (1) help further refine patient selection criteria, (2) better clarify the optimal partial breast irradiation target and technique for each clinical setting, (3) determine when AWBI, standard WBI, or excision alone may be more appropriate, and (4) investigate if further reductions in fractionation schedules are possible.

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.

A cost comparison analysis of adjuvant radiation therapy techniques after breast-conserving surgery.

The aim of this study is to perform a cost analysis to compare adjuvant radiation therapy schedules following breast conserving surgery. Treatment planning and delivery utilization data were modeled for a series of 10 different breast RT techniques. The whole breast (WB) regimens consisted of: (1) Wedge based WB (25 fractions [fx]), (2) WB using IMRT, (3) WBRT with a boost (B), (4) WBRT using IMRT with a B, (5) Canadian WB (16 fx) with 3D-CRT, and (6) Canadian using IMRT. The accelerated partial breast irradiation (APBI) regimens included (7): APBI using 3D-CRT, (8) IMRT, (9) single channel balloon, and (10) multi-channel balloon. Costs incurred by the payer (i.e., direct medical costs) were taken from the 2011 Medicare Fee Schedule. Among all the different regimens examined, Canadian 3D-CRT and APBI 3D-CRT were the least costly whereas WB using IMRT with a B was the most expensive. Both APBI brachytherapy techniques were less costly than conventional WB with a B. In terms of direct medical costs, the technical component accounted for most, if not all, of the disparity among the various treatments. A general trend of decreasing RT costs was observed with further reductions in overall treatment time for WBRT techniques, but not all of the alternative treatment regimens led to similar total cost savings. APBI using brachytherapy techniques was less costly than conventional WBRT with a standard boost.

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.

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.

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.

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.