Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline

This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns.

Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Real-World Evidence on the Use of Endocrine Therapy for Ductal Carcinoma In Situ in Patients Treated With Breast-Conserving Surgery Followed by Postoperative Radiation Therapy: A Brazilian Retrospective Cohort Study.

INTRODUCTION/BACKGROUND: This study aims to evaluate the reproducibility of findings from randomized controlled trials regarding adjuvant hormone therapy (HT) for breast ductal carcinoma in situ (DCIS) in a real-life scenario. MATERIALS/METHODS: This retrospective cohort study used Fundação Oncocentro de São Paulo database. It included DCIS patients DCIS who received breast-conserving surgery and postoperative radiation therapy. The endpoints were local control (LC), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: We analyzed 2192 patients treated between 2000 and 2020. The median FU was 48.99 months. Most patients (53.33%; n = 1169) received adjuvant HT. Patients not receiving adjuvant HT tend to be older (P = .021) and have a lower educational level (P < .001). At the end of FU, 1.5% of patients had local recurrence, and there was no significant difference between groups (P = .19). The 10-year OS and BCSS were 89.4% and 97.5% for adjuvant HT versus 91.5% and 98.5% for no adjuvant HT, respectively, and there were no significant differences between groups. The 10-year OS was 93.25% for medium/high education level versus 87.31% for low (HR for death 0.51; 95% CI, 0.32-0.83; P = .007). CONCLUSIONS: The benefits of adjuvant HT for DCIS were not reproduced in a Brazilian cohort. Education significantly impacted survival and HT usage, reflecting the influence of socioeconomic factors. These findings can allow for more precise interventions.

Receipt of mastectomy and adjuvant radiotherapy following breast conserving surgery (BCS) in New Zealand women with BCS-eligible breast cancer, 2010-2015: an observational study focusing on ethnic differences.

BACKGROUND: Women with early breast cancer who meet guideline-based criteria should be offered breast conserving surgery (BCS) with adjuvant radiotherapy as an alternative to mastectomy. New Zealand (NZ) has documented ethnic disparities in screening access and in breast cancer treatment pathways. This study aimed to determine whether, among BCS-eligible women, rates of receipt of mastectomy or radiotherapy differed by ethnicity and other factors. METHODS: The study assessed management of women with early breast cancer (ductal carcinoma in situ [DCIS] and invasive stages I-IIIA) registered between 2010 and 2015, extracted from the recently consolidated New Zealand Breast Cancer Registry (now Te Rehita Mate Utaetae NZBCF National Breast Cancer Register). Specific criteria were applied to determine women eligible for BCS. Uni- and multivariable analyses were undertaken to examine differences by demographic and clinicopathological factors with a primary focus on ethnicity (Maori, Pacific, Asian, and Other; the latter is defined as NZ European, Other European, and Middle Eastern Latin American and African). RESULTS: Overall 22.2% of 5520 BCS-eligible women were treated with mastectomy, and 91.1% of 3807 women who undertook BCS received adjuvant radiotherapy (93.5% for invasive cancer, and 78.3% for DCIS). Asian ethnicity was associated with a higher mastectomy rate in the invasive cancer group (OR 2.18; 95%CI 1.72-2.75), compared to Other ethnicity, along with older age, symptomatic diagnosis, advanced stage, larger tumour, HER2-positive, and hormone receptor-negative groups. Pacific ethnicity was associated with a lower adjuvant radiotherapy rate, compared to Other ethnicity, in both invasive and DCIS groups, along with older age, symptomatic diagnosis, and lower grade tumour in the invasive group. Both mastectomy and adjuvant radiotherapy rates decreased over time. For those who did not receive radiotherapy, non-referral by a clinician was the most common documented reason (8%), followed by patient decline after being referred (5%). CONCLUSION: Rates of radiotherapy use are high by international standards. Further research is required to understand differences by ethnicity in both rates of mastectomy and lower rates of radiotherapy after BCS for Pacific women, and the reasons for non-referral by clinicians.

Mastectomy margins for ductal carcinoma-in-situ (DCIS): 18 Years of follow-up.

BACKGROUND: In patients undergoing mastectomy for ductal carcinoma in situ (DCIS), the significance of a positive or close (<2 mm) margin and associated recurrence risk is unclear. The study sought to evaluate risk of recurrence in relation to the mastectomy surgical margin. METHODS: A single institution retrospective review of patients with DCIS who underwent mastectomy between 2000 and 2010 was performed. Patient demographics, tumor biology, margin status and adjuvant therapy were recorded. The incidence of local recurrence (LR), distant metastasis were analyzed. RESULTS: A total of 282 patients with DCIS were identified. Overall, 12.3% of patients had a pathological positive/close margin (n = 9 tumor on ink and n = 36 <2 mm). Adjuvant radiation was administered to 11 patients with a positive or close margin. At a median follow-up of 12 years, LR was 3.4% (n = 10). None of the patients with LR had a positive or close margin. Additionally, none of the patients who received radiation developed LR. CONCLUSION: Risk of recurrence after mastectomy for DCIS is low and appears to be unrelated to margin status or the use of radiation therapy.

Outcomes of DCIS treated with breast conserving surgery without radiotherapy on recurrence, survival, and health-related quality of life.

BACKGROUND: Sector resection for Ductal Carcinoma in Situ (DCIS) allows wide excision without compromising breast shape. There are concerns that radiotherapy for some DCIS after sector resection is unnecessary and reduces patient satisfaction and quality of life without affecting survival. This study aimed to investigate whether women with DCIS managed with sector resection without radiotherapy had acceptable rates of recurrence and health-related quality of life outcomes. METHODS: Retrospective study of patients who underwent sector resection for DCIS without adjuvant radiotherapy from 1992 to 2021. Tumour size, grade, necrosis, margins, follow up and time to ipsilateral recurrence was recorded. Patients were posted a BREAST-Q to assess health-related quality of life. RESULTS: One hundred and thirty-eight patients were treated for pure DCIS by two surgeons from 1992 to 2018. One hundred and sixteen patients underwent sector resection, 22 had mastectomy. Average age 61 years. Mean follow up 9.14 years. Recurrence rate after sector resection was 18.97%. 55% were DCIS. Annualized recurrence rate was 2.07%. There were no cancer-related deaths. BREAST-Q completion rate was 44%. Satisfaction with breasts, physical, psychosocial, and sexual well-being scores were significantly higher than normative Australian values and a mixed cohort of women who underwent breast conserving surgery with radiotherapy. CONCLUSION: DCIS can be safely managed with sector resection without radiotherapy and regular long-term follow up. This approach results in low annualized recurrence rates, high levels patient satisfaction and health-related quality of life and should be considered a safe alternative for patients with DCIS to minimize morbidity without affecting cancer survival.

DCIS: When is accelerated partial breast irradiation an option? A meta-analysis on outcomes and eligibility.

BACKGROUND: The natural history of DCIS may not be progression to invasive breast cancer (IBC). Accelerated partial breast irradiation (APBI) has emerged as an alternative to whole breast radiotherapy (WBRT). The purpose of this study was to assess the impact of APBI on DCIS patients. MATERIALS AND METHODS: Eligible studies from 2012 to 2022 were identified in PubMed, Cochrane Library, ClinicalTrials, and ICTRP. A meta-analysis was done comparing recurrence rates, breast-related mortality rates, and adverse events of APBI versus WBRT. A subgroup analysis of 2017 ASTRO Guidelines "Suitable" and "Unsuitable" groups was performed. Forest plots and quantitative analysis were done. RESULTS: Six studies were eligible (3 on APBI versus WBRT, 3 on APBI suitability). All had a low risk of bias and publication bias. The cumulative incidence was the following for APBI and WBRT respectively: IBTR was 5.7% and 6.3% with odds ratio of 1.09, 95% CI [0.84, 1.42], mortality rate was 4.9% and 5.05%, and adverse events was 48.87% and 69.63%. All had no statistical significance between groups. Adverse events were found to favor the APBI arm. Recurrence rate was significantly less in the Suitable group with an odds ratio 2.69, 95% CI [1.56, 4.67], favoring it over the Unsuitable group. CONCLUSION: APBI was comparable to WBRT in terms of recurrence rate, breast cancer-related mortality rate, and adverse events. APBI was not inferior to WBRT and showed better safety in terms of skin toxicity. Patients classified as suitable for APBI had significantly lesser recurrence rate.

Preliminary outcomes of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free-hand catheter implantation in early breast cancer.

BACKGROUND: To evaluate the clinical feasibility of interstitial brachytherapy by intraoperative free-hand catheter implantation in the treatment of early breast cancer after breast-conserving surgery (BCS). METHODS: Between January 2018 and December 2019, 44 patients with early breast cancer after BCS who met the inclusion criteria ≥45 years old, invasive carcinoma ≤3 cm or ductal carcinoma in situ <2.5 cm, estrogen receptor positive, lymph node negative, surgical margin negative, no distant metastasis, and an ECOG performance score ≤1 were enrolled in this phase II single-arm study. The postoperative irradiation field includes the tumor bed plus 2-cm margin in all directions, except in the anterior-posterior direction. The total prescribed tumor dose was 3400 cGy delivered in 10 fractions twice daily at 6-hour intervals. The primary endpoints were acute side effects, late treatment-related toxicity, and cosmetic outcome. The secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: The median follow-up time was 33.5 months (mean, 32.9 months; range, 20-43 months). The cosmetic results were good to very good in 92.3% of the questionnaire respondents. The acute toxicities were mild, and no acute grade 3-4 toxicity was noted. Wound infection was noted in two patients (4.5%). There was only one event of regional lymph node recurrence in one patient. The 3-year LRFS, DMFS, and OS were 100%, and RRFS was 94.7%. For two patients who had a positive lymph node based on their final pathology reports, postoperative irradiation, including whole breast and regional lymph nodes, was added. CONCLUSION: Accelerated partial breast irradiation using interstitial brachytherapy with the intraoperative free-hand catheter implantation technique provides an alternative method of postoperative radiotherapy for selected patients with early breast cancer after BCS with acceptable toxicities.

A Novel Biosignature Identifies Patients With DCIS With High Risk of Local Recurrence After Breast Conserving Surgery and Radiation Therapy.

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.

Optimizing Preventive Adjuvant Linac-Based (OPAL) Radiation: A Phase 2 Trial of Daily Partial Breast Irradiation.

PURPOSE: Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled. METHODS AND MATERIALS: We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost. RESULTS: All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years; 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P = .004), breast pain (P = .004), and physician-reported cosmesis (P < .001). CONCLUSIONS: Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.

Survival outcomes after breast-conserving surgery plus radiotherapy compared with mastectomy in breast ductal carcinoma in situ with microinvasion.

Ductal carcinoma in situ with microinvasion (DCIS-MI) is a subtype of breast cancer with a good prognosis, for which both breast conserving surgery plus radiotherapy (BCS + RT) and mastectomy are feasible surgical methods, but no clear conclusion has been made on the choice of these treatments. We used the Surveillance, Epidemiology and End Results database to extract 5432 DCIS-MI patients. Participants were divided into the BCS + RT group and the mastectomy group. We compared the overall survival (OS) and breast cancer-specific survival (BCSS) of the two groups using the Kaplan-Meier method and Cox regressions before and after propensity score matching (PSM). Before PSM, both univariate and multivariate analyses showed that BCS + RT group had significantly higher OS and BCSS compared with patients in the mastectomy group (P < 0.001). After PSM, the multivariate analysis showed that compared with mastectomy, the BCS + RT showed significantly higher OS and BCSS (HR = 0.676, 95% CI = 0.540-0.847, P < 0.001; HR = 0.565,95% CI = 0.354-0.903, P = 0.017). In addition, the subgroup analysis showed that BCS + RT is at least equivalent to mastectomy with respect to OS and BCSS in any subgroup. For patients with DCIS-MI, the prognosis of BCS + RT was superior to mastectomy.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Local treatment options for young women with ductal carcinoma in situ: A systematic review and meta-analysis comparing breast conserving surgery with or without adjuvant radiotherapy, and mastectomy.

PURPOSE: Young age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women. METHODS: PubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest. RESULTS: We included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50-0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98-1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06-9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes. CONCLUSION: This study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.

Accelerated Partial Breast Irradiation Using External Beam or Intraoperative Electron Radiation Therapy: 5-Year Oncological Outcomes of a Prospective Cohort Study.

PURPOSE: To evaluate the ipsilateral breast tumor recurrence (IBTR) after 2 accelerated partial breast irradiation (APBI) techniques (intraoperative electron radiation therapy [IOERT] and external beam APBI [EB-APBI]) in patients with early-stage breast cancer. METHODS AND MATERIALS: Between 2011 and 2016, women ≥60 years of age with breast carcinoma or Ductal Carcinoma In Situ (DCIS) of ≤30 mm and cN0 undergoing breast-conserving therapy were included in a 2-armed prospective multicenter cohort study. IOERT (1 × 23.3 Gy prescribed at the 100% isodose line) was applied in 1 hospital and EB-APBI (10 × 3.85 Gy daily) in 2 other hospitals. The primary endpoint was IBTR (all recurrences in the ipsilateral breast irrespective of localization) at 5 years after lumpectomy. A competing risk model was used to estimate the cumulative incidences of IBTR, which were compared using Fine and Gray's test. Secondary endpoints were locoregional recurrence rate, distant recurrence, disease-specific survival and overall survival. Univariate Cox regression models were estimated to identify risk factors for IBTR. Analyses were performed of the intention to treat (ITT) population (IOERT n = 305; EB-APBI n = 295), and sensitivity analyses were done of the per-protocol population (IOERT n = 270; EB-APBI n = 207). RESULTS: The median follow-up was 5.2 years (IOERT) and 5 years (EB-APBI). Cumulative incidence of IBTR in the ITT population at 5 years after lumpectomy was 10.6% (95% confidence interval, 7.0%-14.2%) after IOERT and 3.7% (95% confidence interval, 1.2%-5.9%) after EB-APBI (P = .002). The locoregional recurrence rate was significantly higher after IOERT than EB-APBI (12.1% vs 4.5%, P = .001). There were no differences between groups in other endpoints. Sensitivity analysis showed similar results. For both groups, no significant risk factors for IBTR were identified in the ITT population. In the per-protocol population, surgical margin status of the DCIS was the only significant risk factor for developing IBTR in both treatment groups. CONCLUSIONS: Ipsilateral breast tumor recurrences and locoregional recurrence rates were unexpectedly high in patients treated with IOERT, and acceptable in patients treated with EB-APBI.