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.

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.

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.

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.

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.

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.

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.

Early complications of high-dose-rate brachytherapy in soft tissue sarcoma: a comparison with traditional external-beam radiotherapy.

BACKGROUND: Radiotherapy and surgery are routinely utilized to treat extremity soft tissue sarcoma. Multiple radiation modalities have been described, each with advantages and disadvantages, without one modality demonstrating clear superiority over the others. QUESTIONS/PURPOSES: We determined the overall initial complication rate in patients receiving surgery and radiotherapy, which specific complications were found when comparing different modalities, and whether combination therapy increased the overall rate of complications compared with surgery and single-modality radiotherapy. PATIENTS AND METHODS: We retrospectively reviewed the records of 190 patients who received external-beam radiotherapy (141 patients), high-dose-rate brachytherapy (37 patients), or both (12 patients). We evaluated 100 men and 90 women (mean age, 57 years; range, 18-94 years) for tumor size and subtype, comorbidities, stage, grade, margin of resection, type of adjuvant treatment, and complications. Minimum followup was 3 months (mean, 40 months; range, 3-155 months). RESULTS: The most frequent early complications in the high-dose-rate brachytherapy cohort were infection, cellulitis, and seroma and/or hematoma. In the external-beam radiotherapy cohort, chronic edema, fibrosis, and chronic radiation dermatitis were more frequently encountered. The total number of early complications and overall incidence of major complications requiring further surgery were similar among the three cohorts, but a larger number of patients in the high-dose-rate brachytherapy group required subsequent surgery for infection compared with the external-beam radiotherapy group. CONCLUSIONS: High-dose-rate brachytherapy decreases radiation exposure and allows shorter duration of treatment compared with traditional external-beam radiotherapy but has a higher perioperative wound complication rate. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Update on DCIS outcomes from the American Society of Breast Surgeons accelerated partial breast irradiation registry trial.

BACKGROUND: Since the initial reports on use of MammoSite accelerated partial breast irradiation (APBI) for treatment of ductal carcinoma in situ (DCIS), additional follow-up data were collected. We hypothesized that APBI delivered via MammoSite would continue to be well tolerated, associated with a good cosmetic outcome, and carry a low risk for recurrence in patients with DCIS. MATERIALS AND METHODS: From 2002-2004, 194 patients with DCIS were enrolled in a registry trial to assess the MammoSite. Follow-up data were available for all 194 patients. Median follow-up was 54.4 months; 63 patients had at least 5 years of follow-up. Data obtained included patient-, tumor-, and treatment-related factors, and recurrence incidence. RESULTS: Of the 194 patients, 87 (45%) had the MammoSite placed at lumpectomy; 107 patients (55%) had the device placed postlumpectomy. In the first year of follow-up, 16 patients developed a breast infection, though the method of device placement was not associated with infection risk. Also, 46 patients developed a seroma that was associated with applicator placement at the time of lumpectomy (P = 0.001). For patients with at least 5 years of follow-up, 92% had favorable cosmetic results. There were 6 patients (3.1%) who had an ipsilateral breast recurrence, with 1 (0.5%) experiencing recurrence in the breast and axilla, for a 5-year actuarial local recurrence rate of 3.39%. CONCLUSIONS: During an extended follow-up period, APBI delivered via MammoSite continued to be well tolerated for patients with DCIS. Use of this device may make lumpectomy possible for patients who would otherwise choose mastectomy because of barriers associated with standard radiation therapy.

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.

Early breast cancer.

Adoption of urbanised lifestyles together with changes in reproductive behaviour might partly underlie the continued rise in worldwide incidence of breast cancer. Widespread mammographic screening and effective systemic therapies have led to a stage shift at presentation and mortality reductions in the past two decades. Loco-regional control of the disease seems to affect long-term survival, and attention to surgical margins together with improved radiotherapy techniques could further contribute to mortality gains. Developments in oncoplastic surgery and partial-breast reconstruction have improved cosmetic outcomes after breast-conservation surgery. Optimum approaches for delivering chest-wall radiotherapy in the context of immediate breast reconstruction present special challenges. Accurate methods for intraoperative assessment of sentinel lymph nodes remain a clinical priority. Clinical trials are investigating combinatorial therapies that use novel agents targeting growth factor receptors, signal transduction pathways, and tumour angiogenesis. Gene-expression profiling offers the potential to provide accurate prognostic and predictive information, with selection of best possible therapy for individuals and avoidance of overtreatment and undertreatment of patients with conventional chemotherapy. Short-term presurgical studies in the neoadjuvant setting allow monitoring of proliferative indices, and changes in gene-expression patterns can be predictive of response to therapies and long-term outcome.

Five-year outcome of patients classified in the "unsuitable" category using the American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus Panel guidelines for the application of accelerated partial breast irradiation: an analysis of patients treated on the American Society of Breast Surgeons MammoSite® Registry trial.

PURPOSE: We applied the ASTRO Consensus Panel (CP) guidelines for the application of accelerated partial breast irradiation (APBI) to patients treated with this technique on the ASBS MammoSite® registry trial to determine potential differences in outcome of patients classified in the "unsuitable" category. METHODS: Of 1,449 cases treated with APBI on the registry trial, 176 fit the criteria for the unsuitable category: 130 cases were <50 years of age, 13 had positive margins, 38 had positive nodes, 6 had tumors >3 cm, and 9 had an EIC >3 cm. Rates of ipsilateral breast tumor recurrence (IBTR) and regional nodal failure (RNF) were assessed. Median follow-up was 53.6 months. RESULTS: The 5-year actuarial rate of IBTR for unsuitable cases was 5.25% (RNF rate was 0.63%). By comparison, the 5-year actuarial IBTR rates for various subsets of patients were: all 1,449 cases, 3.89% (p = 0.2365); all 1,449 cases excluding unsuitable cases [n =1,273] (3.6%, p =0.1683); invasive only cases [n = 1,255] (3.86%, p = 0.2464); and invasive only cases excluding unsuitable invasive cases [n =1,105] (3.89%, p = 0.2396). On univariate analysis for variables potentially associated with IBTR in all 1,255 cases with invasive cancer (including age, tumor size, nodal status, overall stage, margin status, ER status, presence of an EIC, and ASTRO unsuitable category), only negative ER (-) status was associated with the 5-year rate of IBTR (p = 0002). No other variable (including unsuitable CP designation) was associated with IBTR. CONCLUSIONS: The ASTRO CP guideline designation of unsuitable did not differentiate a subset of patients with a significantly worse rate of IBTR when treated with the MammoSite® breast brachytherapy catheter to deliver APBI.

Factors associated with optimal cosmetic results at 36 months in patients treated with accelerated partial breast irradiation (APBI) on the American Society of Breast Surgeons (ASBrS) MammoSite Breast Brachytherapy Registry Trial.

PURPOSE: To evaluate factors associated with optimal cosmetic results at 36 months for early-stage breast cancer patients enrolled on the American Society of Breast Surgeons (ASBrS) MammoSite Breast Brachytherapy registry trial. MATERIALS AND METHODS: 1,440 patients (1,449 cases) with early-stage breast cancer undergoing breast-conserving therapy were treated with the MammoSite radiation therapy system (RTS) brachytherapy catheter to deliver adjuvant accelerated partial breast irradiation (APBI) (34 Gy in 3.4-Gy fractions). Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good or fair/poor. Median follow-up for surviving patients was 43.0 months (range 0-73.0 months). RESULTS: The percentage of patients with good/excellent cosmetic results at 12, 24, 36, and 48 months were as follows: 94.5% (n = 950/1,005), 93.8% (n = 781/833), 93.1% (n = 683/734), and 90.4% (n = 520/575), respectively. Three-year absolute rates of good/excellent cosmesis were as follows: breast-related wound infection (BWI) (83.3%) versus no BWI (94%), <7 mm skin spacing (87.5%) versus >or=7 mm skin spacing (93.6%). Using multiple regression analysis, factors predictive of worse cosmetic outcome at 36 months included smaller skin spacing [odds ratio (OR) 1.06, confidence interval (CI) 1.01-1.12] and BWI (OR 0.33, CI 0.16-0.70). A predictive model developed showed that presence of a BWI, use of chemotherapy, and skin spacing had the most effect on cosmetic outcomes. However, in patients that did not develop a breast infection, skin spacing and use of chemotherapy had the most effect on cosmesis. CONCLUSION: APBI delivered by MammoSite brachytherapy lead to good/excellent cosmesis in 93% of patients with 3-year follow-up. Breast wound infection, use of chemotherapy, and skin spacing were found to be the three most important predictors of cosmesis at 36 months in our cohort of patients.

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.

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

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

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.