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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. [ABSTRACT FROM AUTHOR]

Background: The American Society for Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) was applied to patients who were treated with this technique on the American Society of Breast Surgeons MammoSite Registry Trial to determine potential differences in clinical outcome based on classification group.Methods: Patients were classified based on the CS groups of "suitable," "cautionary," and "unsuitable." Rates of ipsilateral breast tumor recurrence (IBTR), regional lymph node failure, distant metastases, disease-free survival, cause-specific survival, and overall survival were assessed.Results: Of the 1449 cases who were treated, 1025 patients (71%) could be classified according to the CS groupings, including 419 patients (41%) who fit the "suitable" criteria, 430 patients (42%) who fit the "cautionary" criteria, and 176 patients (17%) who fit the "unsuitable" criteria. At a median follow-up of 53.5 months, the 5-year actuarial rates of IBTR for the "suitable," "cautionary," and "unsuitable" groups were 2.59%, 5.43%, and 5.28%, respectively (P = .1884). Univariate analysis of factors potentially associated with IBTR indicated that negative estrogen receptor status was the only variable associated with IBTR among patients with invasive breast cancer (odds ratio [OR], 4.01; P = .0003). Larger tumor size was associated with a greater risk of distant metastasis (OR, 3.05; P = .0001). Among patients with ductal carcinoma in situ, only age <50 years and close-positive margins were associated with IBTR (OR, 1.12 [P = .0079] and OR, 7.81 [P = .0131], respectively).Conclusions: The ASTRO CS groupings did not differentiate a subset of patients with a significantly worse rate of IBTR when they were treated with the MammoSite breast brachytherapy catheter to deliver APBI. [ABSTRACT FROM AUTHOR]

Purpose: NRG Oncology (NRG)/NSABP B-39/RTOG 0413 compared whole-breast irradiation (WBI) to accelerated partial-breast irradiation (APBI). APBI was not equivalent to WBI in local tumor control. Secondary outcome was Quality-of-life (QOL)., Methods: The QOL sub-study used validated self-report questionnaires including the Breast Cancer Treatment Outcome Scale (BCTOS) and SF-36 vitality scale. Assessments occurred: before randomization, at treatment completion (chemotherapy or radiotherapy), 4-weeks later, at 6-, 12-, 24-, and 36-months. Primary aims: cosmesis change equivalency (baseline to 3 years; a priori margin of equivalence 0.4 standard deviations) and fatigue change superiority (baseline to end-of-treatment (EOT)) for APBI vs WBI, by patient groups treated with or without chemotherapy when appropriate., Results: From 3/21/05-5/25/09, 975 patients enrolled in this sub-study; 950 had follow-up data. APBI had 3-year cosmesis equivalent to WBI (95%CI,-0.0001-0.16; equivalence margin -0.22-0.22) in all patients. The APBI group without chemotherapy had less EOT fatigue (p = .011; mean score APBI 63 vs WBI 59); APBI group receiving chemotherapy had worse EOT fatigue (p = .011; APBI 43 vs WBI 49). The APBI group reported less pain (BCTOS) at EOT (WBI 2.29 vs APBI 1.97), but worse pain at 3-years (WBI 1.62 vs APBI 1.71). APBI patients reported greater convenience of care than with WBI and reported less symptom severity at EOT and 4-weeks later., Conclusion: Cosmetic outcomes were similar for APBI and WBI groups, with small statistically significant differences in other outcomes that varied over time. Differences in fatigue and other symptoms appeared to resolve by ≥ 6 months. APBI may be preferred by some patients, for whom extended treatment is burdensome., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations., Methods: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations., Results: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria., Conclusions: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients., Trial Registration: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 )., (© 2024. The Author(s).)

Purpose: The efficacy and long-term safety of hypofractionated whole breast irradiation (HF-WBI) have been established through multiple randomized trials, yet data about acute toxicities remain more limited. Since 2013, our group has prospectively collected acute toxicity data from weekly treatment evaluations and additional assessment after completion. In 2016, we intentionally shifted the posttreatment assessment follow-up visit from 1 month to 2 weeks to evaluate for missed acute toxicity occurring in that immediate posttreatment window. Here, we report whether 2-week follow-up has resulted in increased detection of acute toxicities compared with 4-week follow-up., Methods and Materials: We prospectively compared acute toxicity for patients treated with HF-WBI between January 1, 2013, and August 31, 2015 (4 week follow-up cohort) to patients treated between January 1, 2016, and August 31, 2018 (2 week follow-up cohort). Analyses included a multivariable model that adjusted for other factors known to correlate with toxicity. We prospectively defined acute toxicity as maximum breast pain (moderate or severe rating) and/or occurrence of moist desquamation reported 7 days before the completion of radiation therapy (RT) until 42 days after completion., Results: A total of 2689 patients who received postlumpectomy radiation and boost were analyzed; 1862 patients in the 2-week follow-up cohort and 827 in the 4-week follow-up cohort. All acute toxicity measures assessed were statistically similar between follow-up cohorts when compared in an unadjusted fashion. Overall acute composite toxicity was 26.4% and 27.7% for patients in the 4-week follow-up and 2-week follow-up cohorts, respectively. Overall acute composite toxicity remained similar between follow-up cohorts in a multivariable, adjusted model and was significantly related to patient's age, body mass index, smoking status, and treatment technique (intensity-modulated RT vs 3-dimensional conformal radiation therapy) but not follow-up cohort., Conclusions: An earlier posttreatment follow-up for HF-WBI patients did not reveal a significant increased incidence of acute toxicities at 2 weeks compared with 4 weeks. This study provides physicians and patients with additional data on the safety and tolerability of HF-WBI for early stage breast cancer., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Limiting cardiac radiation dose is important for minimizing long-term cardiac toxicity in patients with left-sided early-stage breast cancer., Methods and Materials: Prospectively collected dosimetric data were analyzed for patients undergoing moderately hypofractionated radiation therapy to the left breast within the Michigan Radiation Oncology Quality Consortium from 2016 to 2022. The mean heart dose (MHD) goal was progressively tightened from ≤2 Gy in 2016 to MHD ≤ 1.2 Gy in 2018. In 2021, a planning target volume (PTV) coverage goal was added, and the goal MHD was reduced to ≤1 Gy. Multivariate logistic regression models were developed to assess for covariates associated with meeting the MHD goals in 2016 to 2020 and the combined MHD/PTV coverage goal in 2021 to 2022., Results: In total, 4165 patients were analyzed with a median age of 64 years. Overall average cardiac metric compliance was 91.7%. Utilization of motion management increased from 41.8% in 2016 to 2020 to 46.5% in 2021 to 2022. Similarly, use of prone positioning increased from 12.2% to 22.2% in these periods. On multivariate analysis in the 2016 to 2020 cohort, treatment with motion management (odds ratio [OR], 5.20; 95% CI, 3.59-7.54; P < .0001) or prone positioning (OR, 3.21; 95% CI, 1.85-5.57; P < .0001) was associated with meeting the MHD goal, while receipt of boost (OR, 0.25; 95% CI, 0.17-0.39; P < .0001) and omission of hormone therapy (OR, 0.65; 95% CI, 0.49-0.88; P = .0047) were associated with not meeting the MHD goal. From 2021 to 2022, treatment with motion management (OR, 1.89; 95% CI, 1.12-3.21; P = .018) or prone positioning (OR, 3.71; 95% CI, 1.73-7.95; P = .0008) was associated with meeting the combined MHD/PTV goal, while larger breast volume (≥1440 cc; OR, 0.34; 95% CI, 0.13-0.91; P = .031) was associated with not meeting the combined goal., Conclusions: In our statewide consortium, high rates of compliance with aggressive targets for limiting cardiac dose were achievable without sacrificing target coverage., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To analyze the dosimetric and toxicity outcomes of patients treated with postoperative stereotactic partial breast irradiation (S-PBI)., Methods: We identified 799 women who underwent S-PBI at our institution between January 2016 and December 2022. The most commonly used dose-fraction and technique were 30 Gy in 5 fractions (91.7 %) and a robotic stereotactic radiation system with real-time tracking (83.7 %). The primary endpoints were dosimetric parameters and radiation-related toxicities. For comparison, a control group undergoing ultra-hypofractionated whole breast irradiation (UF-WBI, n = 468) at the same institution was selected., Results: A total of 815 breasts from 799 patients, with a median planning target volume (PTV) volume of 89.6 cm 3 , were treated with S-PBI. Treatment plans showed that the mean and maximum doses received by the PTV were 96.2 % and 104.8 % of the prescription dose, respectively. The volume of the ipsilateral breast that received 50 % of the prescription dose was 32.3 ± 8.9 %. The mean doses for the ipsilateral lung and heart were 2.5 ± 0.9 Gy and 0.65 ± 0.39 Gy, respectively. Acute toxicity occurred in 175 patients (21.5 %), predominantly of grade 1. Overall rate of late toxicity was 4 % with a median follow-up of 31.6 months. Compared to the UF-WBI group, the S-PBI group had comparably low acute toxicity (21.5 % vs. 25.2 %, p = 0.12) but significantly lower dosimetric parameters for all organs-at-risks (all p < 0.05)., Conclusion: In this large cohort, S-PBI demonstrated favorable dosimetric and toxicity profiles. Considering the reduced radiation exposure to surrounding tissues, external beam PBI with advanced techniques should at least be considered over traditional WBI-based approaches for PBI candidates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: The PREVENT randomized trial assessed progression to chronic breast cancer-related lymphedema (cBCRL) after intervention triggered by bioimpedance spectroscopy (BIS) or tape measurement (TM). This secondary analysis identifies cBCRL risk factors on the basis of axillary treatment., Methods: Between June 2014 and September 2018, 881 patients received sentinel node biopsy (SNB; n = 651), SNB + regional node irradiation (RNI; n = 58), axillary lymph node dissection (ALND; n = 85), or ALND + RNI (n = 87). The primary outcome was the 3-year cBCRL rate requiring complex decongestive physiotherapy (CDP)., Results: After a median follow-up of 32.8 months (IQR, 21-34.3), 69 of 881 patients (7.8%) developed cBCRL. For TM, 43 of 438 (9.8%) developed cBCRL versus 26 of 443 (5.9%) for BIS ( P = .028). The 3-year actuarial risk of cBCRL was 4.4% (95% CI, 2.7 to 6.1), 4.2% (95% CI, 0 to 9.8), 25.8% (95% CI, 15.8 to 35.8), and 26% (95% CI, 15.3 to 36.7). Rural residence increased the risk in all groups. For SNB, neither RNI (SNB, 4.1% v SNB + RNI, 3.4%) nor taxane (4.4%) increased cBCRL, but risk was higher for patients with a BMI of ≥30 (6.3%). For SNB + RNI, taxane use (5.7%) or supraclavicular fossa (SCF) radiation (5.0%) increased cBCRL. For ALND patients, BMI ≥25 or chemotherapy increased cBCRL. For ALND + RNI, most patients received SCF radiation and taxanes, so no additional risk factors emerged., Conclusion: The extent of axillary treatment is a significant risk factor for cBCRL. Increasing BMI, rurality, SCF radiation, and taxane chemotherapy also increase risk. These results have implications for a proposed risk-based lymphedema screening, early intervention, and treatment program.

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., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Breast cancer-related lymphedema (BCRL) represents a significant concern for patients following breast cancer treatment, and assessment for BCRL represents a key component of survivorship efforts. Growing data has demonstrated the benefits of early detection and treatment of BCRL. Traditional diagnostic modalities are less able to detect reversible subclinical BCRL while newer techniques such as bioimpedance spectroscopy (BIS) have shown the ability to detect subclinical BCRL, allowing for early intervention and low rates of chronic BCRL with level I evidence. We present updated clinical practice guidelines for BIS utilization to assess for BCRL., Methods and Results: Review of the literature identified a randomized controlled trial and other published data which form the basis for the recommendations made. The final results of the PREVENT trial, with 3-year follow-up, demonstrated an absolute reduction of 11.3% and relative reduction of 59% in chronic BCRL (through utilization of compression garment therapy) with BIS as compared to tape measurement. This is in keeping with real-world data demonstrating the effectiveness of BIS in a prospective surveillance model. For optimal outcomes patients should receive an initial pre-treatment measurement and subsequently be followed at a minimum quarterly for first 3 years then biannually for years 4-5, then annually as appropriate, consistent with previous guidelines; the target for intervention has been changed from a change in L-Dex of 10 to 6.5. The lack of pre-operative measure does not preclude inclusion in the prospective surveillance model of care., Conclusion: The updated clinical practice guidelines present a standardized approach for a prospective model of care using BIS for BCRL assessment and supported by evidence from a randomized controlled trial as well as real-world data., (© 2022. The Author(s).)

Purpose: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT., Methods and Materials: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were classified into 3 biosignature risk groups using the decision score (DS) and the RRt category: (1) Low Risk (DS ≤2.8 without RRt), (2) Elevated Risk (DS >2.8 without RRt), and (3) Residual Risk (DS >2.8 with RRt). Total and invasive IBR rates were assessed by risk group and treatment., Results: In patients at low risk, there was no significant difference in IBR rates with or without RT (total, P = .8; invasive IBR, P = .7), and there were low overall 10-year rates (total, 5.1%; invasive, 2.7%). In patients with elevated risk, IBR rates were decreased with RT (total: hazard ratio [HR], 0.25; P < .001; invasive: HR, 0.28; P = .005); 10-year rates were 20.6% versus 4.9% (total) and 10.9% versus 3.1% (invasive). In patients with residual risk, although IBR rates decreased with RT after BCS (total: HR, 0.21; P < .001; invasive: HR, 0.29; P = .028), IBR rates remained significantly higher after RT compared with patients with elevated risk (HR, 2.5; 95% CI, 1.2-5.4; P = .018), with 10-year rates of 42.1% versus 14.7% (total) and 18.3% versus 6.5% (invasive)., Conclusions: The novel biosignature identified patients with 3 distinct risk profiles: Low Risk patients with a low recurrence risk with or without adjuvant RT, Elevated Risk patients with excellent outcomes after BCS plus RT, and Residual Risk patients with an elevated recurrence risk remaining after BCS plus RT, warranting potential intensified or alternative treatment approaches., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated whether the use of chemotherapy before whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxic effects or worse cosmetic outcome compared with WBI alone., Methods and Materials: We identified 6754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a statewide consortium. We reported rates of 4 toxic effects: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxic effect measure (including moist desquamation and either patient- or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at 1 year after WBI. Successive multivariable models were constructed to estimate the effect of chemotherapy on these outcomes., Results: Rates of moist desquamation, patient-reported pain, composite acute toxic effects, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3895 patients receiving HWBI. Receipt of chemotherapy before CWBI was not associated with higher rates of patient-reported pain, composite acute toxic effects, or impaired cosmetic outcome compared with CWBI without chemotherapy but was associated with more moist desquamation (odds ratio, 1.32 [1.07-1.63]; P = .01). Receipt of chemotherapy before HWBI was not associated with higher rates of any of the 4 toxic effects compared with HWBI alone., Conclusions: In this cohort, use of chemotherapy before WBI was generally well tolerated. CWBI with chemotherapy but not HWBI with chemotherapy was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at 1 year were comparable in patients receiving chemotherapy before either CWBI or HWBI. These data support the use of HWBI after chemotherapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer., Methods and Materials: Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups., Results: The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P = .89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P = .95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P = .28)., Conclusions: Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT ® ) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians' recommendations for adjuvant RT., Methods: The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations., Results: Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors., Conclusions: DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade., (© 2021. The Author(s).)

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., (© 2021. Society of Surgical Oncology.)

Purpose: To compare the risk of subclinical breast cancer-related lymphedema (sBCRL) using bioimpedance spectroscopy (BIS) or tape measure (TM) by the extent of axillary surgery and regional nodal irradiation (RNI)., Methods and Materials: Patients were randomized to surveillance with TM or BIS. A BIS ≥6.5 L-Dex units or TM volume change ≥5 and <10% above presurgical baselines "triggered" sBCRL. The incidence of sBCRL by sentinel node biopsy or axillary lymph node dissection (ALND) with or without RNI was examined for 484 patients. Radiation was categorized as "limited RNI" (axilla level I/II only) or "extensive RNI" (axilla level III or supraclavicular fossa with or without level I/II)., Results: At a median follow-up of 20.5 months, 109 of 498 patients (21.9%) triggered sBCRL (BIS 13.5% vs TM 25.6%; P <.001). In patients not receiving RNI, BIS triggered 12.9% of patients undergoing SNB and 25.0% undergoing ALND (P = .18). Extensive RNI significantly increased triggering with BIS versus no RNI after sentinel node biopsy (SNB; 33.3% vs 12.9%; P = .03) but not ALND (30.8% vs 25.0%; P = .69). Triggering by TM was greater than 25% for most subgroups and was inferior to BIS in discriminating the risk of sBCRL by utilization of RNI or axillary surgery., Conclusions: The lower triggering rates with BIS and its better discrimination of the risk of sBCRL by receipt and type of RNI compared with TM support its use for posttreatment surveillance to detect sBCRL and to initiate early intervention. The risk of sBCRL increased with more extensive axillary treatment. Patients having ALND or extensive RNI require close surveillance for BCRL. Longer follow-up is required to determine rates of progression to clinical lymphedema., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate patterns of failure in institutional credentialing submissions to NRG/RTOG 1005 with the aim of improving the quality and consistency for future breast cancer protocols., Methods and Materials: NRG/RTOG 1005 allowed the submission of 3-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and simultaneous integrated boost (SIB) breast plans. Credentialing required institutions to pass a 2-step quality assurance (QA) process: (1) benchmark, requiring institutions to create a plan with no unacceptable deviations and ≤1 acceptable variation among the dose volume (DV) criteria, and (2) rapid review, requiring each institution's first protocol submission to have no unacceptable deviations among the DV criteria or contours. Overall rates, number of resubmissions, and reasons for resubmission were analyzed for each QA step., Results: In total, 352 institutions participated in benchmark QA and 280 patients enrolled had rapid review QA. Benchmark initial failure rates were similar for 3DCRT (18%), IMRT (17%), and SIB (18%) plans. For 3DCRT and IMRT benchmark plans, ipsilateral lung most frequently failed the DV criteria, and SIB DV failures were seen most frequently for the heart. Rapid review contour initial failures (35%) were due to target rather than organs at risk. For 29% of the rapid review initial failures, the planning target volume boost eval volume was deemed an unacceptable deviation., Conclusions: The review of the benchmark and rapid review QA submissions indicates that acceptable variations or unacceptable deviations for the ipsilateral lung and heart dose constraints were the most commonly observed cause of benchmark QA failure, and unacceptable deviations in target contouring, rather than normal structure contouring, were the most common cause of rapid review QA failure. These findings suggest that a rigorous QA process is necessary for high quality and homogeneity in radiation therapy in multi-institutional trials of breast cancer to ensure that the benefits of radiation therapy far outweigh the risks., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To report 6-year outcomes from a phase I/II trial using balloon-based brachytherapy to deliver APBI in 2 days., Methods: A total of 45 patients with early-stage breast cancer received adjuvant APBI in 2 days with high-dose rate (HDR) brachytherapy totaling 2800 cGy in 4 fractions (700 cGy BID) using a balloon-based applicator as part of a prospective phase I/II clinical trial. All patients had negative margins and skin spacing ≥8 mm. We evaluated toxicities (CTCAE v3) as well as ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis, disease-free survival, cause-specific survival, and overall survival., Results: Median age and tumor size were 66 years old (48 to 83) and 0.8 cm (0.2 to 2.3 cm), respectively. Four percent of patients were N1 (n=2) and 73% were estrogen receptor (ER) positive (n=32). Median follow-up was 6.2 years (2.4 to 8.0 y). Nearly all toxicities at 6 years were grade 1 to 2 except 1 instance of grade 3 telangiectasia (2%). Eleven percent (n=5) of patients had chronic asymptomatic fat necrosis whereas asymptomatic seromas were noted on mammogram in 13% of cases (n=6). Cosmesis at last follow-up was good or excellent in 91% of cases (n=40) and fair in 9% (n=4). Two of the previously reported rib fractures healed with conservative measures. There were no IBTR or RNF (6 y IBTR/RNF rate 0%); however, 2 patients experienced distant metastasis (4% at 6 y). The 6-year actuarial disease-free survival, cause-specific survival, and overall survival were 96%, 100%, and 93%, respectively., Conclusions: Hypofractionated 2-day APBI using brachytherapy resulted in excellent clinical outcomes with acceptable chronic toxicities.

Background: This analysis was performed to assess the impact of early intervention following prospective surveillance using bioimpedance spectroscopy (BIS) to detect and manage breast cancer-related lymphedema (BCRL)., Methods: From 8/2010 to 12/2016, 206 consecutive patients were evaluated with BIS. The protocol included pre-operative assessment with L-Dex as well as post-operative assessments at regular intervals. Patients with L-Dex scores >10 from baseline were considered to have subclinical BCRL and were treated with over-the-counter (OTC) compression sleeve for 4 weeks. High-risk patients were defined as undergoing axillary lymph node dissection (ALND), receiving regional nodal irradiation (RNI), or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP)., Results: Median follow-up was 25.9 months. Overall, 17% of patients had one high-risk feature, 8% two, and 7% had three. 9.8% of patients were diagnosed with subclinical BCRL with highest rates seen following ALND (23 vs. 7%, p = 0.01). Development of subclinical BCRL was associated with ALND and receipt of RNI. At last follow-up, no patients (0%) developed chronic, clinically detectable, BCRL. Subset analysis was performed of the 30 patients undergoing ALND. Median number of nodes removed was 18 and median number of positive nodes was 2. 77% received taxane chemotherapy, 62% axillary RT, and 48% had elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three. Seven patients (23%) had abnormally elevated L-Dex scores at some point during follow-up. To date, none has required CDP., Conclusions: The results of this study support prospective surveillance utilizing BIS initiated pre-operatively with subsequent post-operative follow-up measurements for the detection of subclinical BCRL. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with no cases progressing to chronic, clinically detectable BCRL even in very high-risk patients.

In the original publication of the article, under the heading, Study limitations in the Discussion section, the second paragraph, fifth sentence was published incorrectly as "Patients with an L-Dex increase of ≥ 5.5 undergo…sleeve for 4 weeks".

Background: The purpose of the study was to determine outcomes for patients treated with accelerated partial breast irradiation (APBI) on the basis of breast cancer subtype (BCST)., Patients and Methods: Our single-institution, institutional review board-approved APBI database was queried for patients who had complete testing results for the estrogen (ER), progesterone (PR), and HER2/neu receptors to determine outcomes for each BCST. Women were assigned as luminal A (LA), luminal B (LB), HER2, and basal BCST using their ER, PR, and HER2/neu receptor status. Degree of ER expression supplemented the receptor-based luminal BCST assignment. Two hundred seventy-eight patients had results for all 3 receptors (LA = 164 [59%], LB = 81 [29%], HER2 = 5 [2%], basal = 28 [10%]), which were submitted for analysis (ipsilateral breast tumor recurrence [IBTR], regional nodal failure, distant metastasis [DM], disease-free survival [DFS], cause-specific survival [CSS], and overall survival [OS])., Results: Median follow-up was 5.4 years (range, 0.1-12.4 years). Basal and HER2 subtype patients had higher histologic grades (Grade 3 = 75% vs. 10% LA/LB; P < .001), larger tumors (13.0 mm basal vs. 10.7 mm LA/LB; P = .059), and were more likely to receive chemotherapy (68% vs. 15% LA/LB; P < .001). Margin and nodal status were similar among BCSTs. At 5 years, IBTR rates were similar (1.8%, 2.9%, 0%, and 4.8%) for LA, LB, HER2, and basal subtypes, respectively (P = .62). DM was only seen in LA (2.9%) and LB (1.3%) (P = .83). DFS (95%-100%), CSS (97%-100%), and OS (80%-100%) were not statistically different (P = .97, .87, .46, respectively)., Conclusion: Five-year local control rates after breast-conserving surgery, APBI, and appropriate systemic therapy are excellent for luminal, HER2, and basal phenotypes of early-stage breast cancer; however, further study of receptor subtype effect on risk stratification in early-stage breast cancer is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

With improved breast cancer survivorship, lymphedema of the arm is a growing concern for many patients following treatment. Diagnosis and management of breast cancer related lymphedema (BCRL) is often delayed due to low sensitivity diagnostic techniques and a failure to incorporate BCRL assessments into standard clinical practice. Bioimpedance spectroscopy (BIS) is an increasingly utilized diagnostic technique that allows for the subclinical detection of BCRL, prior to clinically evident disease. We provide a summary of the data supporting the early detection and treatment of BCRL, a comparison of BCRL diagnostic modalities and data supporting the utilization of BIS. Finally, clinical practice guidelines will be provided to allow for the incorporation of BIS into the standard management of breast cancer patients prior to and following locoregional and systemic therapy. These clinical practice guidelines offer clinicians a method to introduce bioimpedance into routine breast cancer care. With increasing focus on BCRL, such protocols will allow for prospective evaluation of patients and early diagnosis and treatment., (© 2016 Wiley Periodicals, Inc.)

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., Competing Interests: R.R.K. reports other support from Cianna Medical, grants from Elekta, outside the submitted work., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To examine utilization trends of accelerated partial breast irradiation (APBI) in the American College of Surgeons' National Cancer Database and changes in APBI use after the 2009 publication of the American Society for Radiation Oncology (ASTRO) guidelines., Methods and Materials: A total of 399,705 women were identified who were diagnosed from 2004 to 2011 with nonmetastatic invasive breast cancer or ductal carcinoma in situ who were treated with breast-conserving surgery and radiation therapy to the breast. Patients were divided by the type of treatment received (whole breast irradiation or APBI) and by suitability to receive APBI as defined by the ASTRO guidelines. Logistic regression was applied to study APBI use overall and within guideline categorization, and a multivariable model was created to determine predictors of treatment with brachytherapy-based APBI based on guideline categorization., Results: For all patients, APBI use increased, from 3.8% in 2004 to 10.6% in 2011 (P<.0001). Overall rates of APBI utilization were higher among "suitable" than "cautionary"/"unsuitable" patients (14.8% vs 7.1%, P<.0001). The majority of APBI treatment was delivered using brachytherapy, for which use peaked in 2008. Starting in 2009, among "suitable" patients, utilization of APBI via brachytherapy plateaued, whereas for "cautionary"/"unsuitable" patients, treatment with brachytherapy-based APBI declined and then plateaued., Conclusion: Use of APBI across all patient groups increased from 2004 through 2008. After publication of the ASTRO APBI guidelines in 2009, rates of brachytherapy-based APBI treatment plateaued among "suitable" patients and declined and then plateaued among "cautionary"/"unsuitable" patients. Our study highlights how large national databases can be used to assess national trends in radiation use in response to the publication of guidelines., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ductal carcinoma in situ of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with ductal carcinoma in situ include mastectomy or breast-conserving therapy. Although several randomized trials have confirmed a >50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared with breast-conserving surgery alone, controversy persists regarding whether or not RT is needed in selected "low-risk" patients. Over the past two decades, two prospective single-arm studies and one randomized trial have been performed and confirm that the omission of RT after surgery is associated with higher rates of local recurrence even after selecting patients with optimal clinical and pathologic features. Importantly, these trials have failed to consistently and reproducibly identify a low-risk cohort of patients (based on clinical and pathologic features) that does not benefit from RT. As a result, adjuvant RT is still advocated in the majority of patients, even in low-risk cases. Future research is moving beyond traditional clinical and pathologic risk factors and instead focusing on approaches such as multigene assays and biomarkers with the hopes of identifying truly low-risk patients who may not require RT. However, recent studies confirm that even low-risk patients identified from multigene assays have higher rates of local recurrence with local excision alone than would be expected with the addition of RT.