Conventional Whole-breast Irradiation Research Articles

Special Techniques of Adjuvant Breast Carcinoma Radiotherapy.

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5-7 weeks of daily treatments, has been reduced to 3-4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes.

NRG RTOG 1005: A Phase III Trial of Hypo Fractionated Whole Breast Irradiation with Concurrent Boost vs. Conventional Whole Breast Irradiation Plus Sequential Boost Following Lumpectomy for High Risk Early-Stage Breast Cancer

<h3>Purpose/Objective(s)</h3> Randomized trials support a supplemental radiation dose (Boost) to the lumpectomy (L) cavity region after whole breast irradiation (WBI), providing a 20-30% relative reduction of in-breast recurrence (IBR); with the disadvantage that it extends treatment duration ⁓ 1 week. Hypofractionated WBI (H-WBI) in ≤ 3 weeks is used after L to deliver adjuvant WBI with acceptable toxicity and comparable IBR as conventional WBI (C-WBI) 50 Gy in 2 Gy fractions (F). NRG RTOG 1005 sought to determine whether a boost delivered concomitantly with H-WBI over 15 F is non-inferior for IBR compared to boost delivered sequentially after C-WBI in patients (pts) considered at High Risk of IBR. <h3>Materials/Methods</h3> Protocol-specified High Risk pts post L with stages 0, I & II breast cancer were randomized to C-WBI 50 Gy in 25 F or 42.7 Gy in 16 F plus sequential boost of 12 Gy in 6 F or 14 Gy in 7 F (Arm I) or H-WBI 40 Gy in 15 F plus concomitant boost of 8 Gy in 15 F of 0.53 Gy per day (Arm II). Radiation was target based 3-dimensional conformal radiation therapy (3DCRT) or intensity modulated radiation therapy (IMRT) and quality review (QA) was required. Stratification was by age (<50 vs ≥ 50), adjuvant chemotherapy (Y vs N), ER status (+ vs -) and histologic grade (1, 2 v 3). The primary endpoint is IBR. Assuming Arm I 5‐year IBR of 1.59%, 90% CI upper bound hazard ratio (HR) of 2.12 and 1‐sided significance level = 0.05, 2150 pts with at least 46 IBR events provide >80% power to conclude non‐inferiority. IBR was analyzed comparing the cause-specific hazards. Adverse Events (AE) were graded with NCI CTCAE v4. Physician-reported NRG-RTOG Global Cosmetic Score (GCS) was grouped as excellent/good vs fair/poor, and arms compared with chi-square. <h3>Results</h3> 2262 of 2354 randomized pts were eligible (Arm I n=1124; Arm II n=1138). Median age 55 years, 34% Stage II, 52% grade 3, 30% ER-, 17% close/+ margins consistent with a "High Risk" population. Radiation was 3DCRT 81%, IMRT 19%, and the QA was per protocol 81% and 88% on Arm I vs II, respectively. With a median follow-up of 7.3 years and 56 IBR events, the 5 and 7-year IBR were 2.0% and 2.2% on Arm I and 1.9% and 2.6% on Arm II. The non-inferiority comparison (Arm I reference level) resulted in a HR (90% CI): 1.32 (0.84, 2.05) and p = 0.039, thus meeting non-inferiority. No differences in AEs noted between arms, with low rates of ≥ grade 3 treatment-related AEs, 3.3% vs 3.5% for Arm I vs II, respectively (p=0.79). No difference in 3-year excellent/good cosmesis by arm: 86% for Arm I vs 84% Arm II (p=0.61). <h3>Conclusion</h3> Concomitant boost with H-WBI results in non-inferior IBR compared to sequential boost after C-WBI in high-risk cases and reduces overall treatment time. Using target based 3DCRT or IMRT, there are no differences in toxicity or cosmetic outcome for concomitant v sequential boost or the WBI fractionation regimen.

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

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. 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). 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). 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. 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.

Abstract P3-19-07: Hypofractionated and conventional whole-breast radiotherapy for breast cancer patients: Financial risk and expenditures in the U.S. 2008-2017

Abstract Background: Rising cancer care expenditures and technological advancement of shorter radiotherapy regimens have drawn significant attention to the use of hypofractionated radiotherapy in clinical care. We examine the costs of hypofractionated (HF-WBI) compared to conventional whole breast irradiation (CF-WBI) in the U.S. through 2017 and investigate the influences of patient characteristics and commercial insurance on HF-WBI use. Methods: In a retrospective study using private employer-sponsored insurance claims, a pooled cross-sectional evaluation of radiotherapy in patients with commercial insurance was performed from 2008-2017. The study population included female patients with early-stage breast cancer treated with lumpectomy and whole-breast irradiation. HF-WBI is defined as receipt of 15-24 radiation fractions and/or radiation fractions delivered between 21-31 days. CF-WBI is defined as receipt of 25-40 fractions and/or radiation fractions delivered between 39-120 days. The primary outcomes and measures were the use of HF-WBI and CF-WBI and total radiotherapy expenditures, including costs incurred by insurers and patient out-of-pocket expenses. Results: A total of 15,869 women received HF-WBI and 59,328 received CF-WBI. HF-WBI use increased from 2008 to 2017. Community-level factors like a higher proportion of college graduates and greater mixed racial composition were associated with increased HF-WBI use. No association was observed between insurance plan characteristics and the likelihood of receiving HF-WBI. The mean insurer-paid radiotherapy expenditures were significantly lower for HF-WBI vs. CF-WBI (adjusted difference $6,375, 95% CI $6,147-$6,603). The mean patient out-of-pocket expenditure for HF-WBI was $139 less than that of CF-WBI (Table 1). Geographic variation existed across U.S. states in HF-WBI use (range: 9.6%-36.2%). There was no consistent relationship across states between the utilization of HF-WBI and the corresponding average cost differences for HF-WBI relative to CF-WBI. Conclusions: If trends continue, HF-WBI will soon become the dominant form of radiation treatment in the U.S. Although HF-WBI represents significant savings to the health care system and individual patients, no evidence indicated that a financial disincentive slowed the adoption of HF-WBI. Therefore, multi-level approaches, including individuals, the community, and health policy, should be utilized to promote cost-effective cancer care. Table 1.Radiotherapy-related expenditures for breast cancer patients aged &amp;lt;65 yrs with commercial insurance plans.aRadiotherapy TypeDifferences, US $bCF-WBIHF-WBIa2008-2017 [Adjusted Mean (95% CI), US $b]Total costs23,286 (23,158 to 23,415)16,763 (16,583 to 16,945)6,253 (6,294 to 6,751)Insurer paid22,751 (22,623 to 22,880)16,376 (16,196 to 16,557)6,375 (6,147 to 6,603)Patient OOP costs502 (491 to 513)363 (206 to 229)139 (119 to 160)aMultivariable generalized linear models with Gamma distribution and log link, with the adjustment for year of radiotherapy, state of beneficiary health plan, age at the time of radiotherapy, type of breast cancer diagnosis, receipt of chemotherapy, Charlson comorbidity index, community education level (% in the community with a college degree or higher), and type of insurance plan. All the differences were statistically significant with p&amp;lt;0.0001. bAll expenditures were rounded up to the nearest dollar amount in 2017 U.S. dollars after adjusting for inflation. CF-WBI: conventional fractionated whole breast irradiation therapy. HF-WBI: hypofractionated WBI. OOP: out of pocket. CI: confidence intervals. Citation Format: Loren Saulsberry, Chuanhong Liao, Dezheng Huo. Hypofractionated and conventional whole-breast radiotherapy for breast cancer patients: Financial risk and expenditures in the U.S. 2008-2017 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-07.

Partial breast irradiation versus whole breast radiotherapy for early breast cancer.

Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast-conserving therapy for early-stage breast cancer. On 27 August 2020, we searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and three trial databases. We searched for grey literature: OpenGrey (September 2020), reference lists of articles, conference proceedings and published abstracts, and applied no language restrictions. Randomised controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. Two review authors (BH and ML) performed data extraction, used Cochrane's risk of bias tool and resolved any disagreements through discussion, and assessed the certainty of the evidence for main outcomes using GRADE. Main outcomes were local recurrence-free survival, cosmesis, overall survival, toxicity (subcutaneous fibrosis), cause-specific survival, distant metastasis-free survival and subsequent mastectomy. We entered data into Review Manager 5 for analysis. We included nine RCTs that enrolled 15,187 women who had invasive breast cancer or ductal carcinoma in-situ (6.3%) with T1-2N0-1M0 Grade I or II unifocal tumours (less than 2 cm or 3 cm or less) treated with breast-conserving therapy with negative margins. This is the second update of the review and includes two new studies and 4432 more participants. Local recurrence-free survival is probably slightly reduced (by 3/1000, 95% CI 6 fewer to 0 fewer) with the use of PBI/APBI compared to WBRT (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 8 studies, 13,168 participants; moderate-certainty evidence). Cosmesis (physician/nurse-reported) is probably worse (by 63/1000, 95% CI 35 more to 92 more) with the use of PBI/APBI (odds ratio (OR) 1.57, 95% CI 1.31 to 1.87; 6 studies, 3652 participants; moderate-certainty evidence). Overall survival is similar (0/1000 fewer, 95% CI 6 fewer to 6 more) with PBI/APBI and WBRT (HR 0.99, 95% CI 0.88 to 1.12; 8 studies, 13,175 participants; high-certainty evidence). Late radiation toxicity (subcutaneous fibrosis) is probably increased (by 14/1000 more, 95% CI 102 more to 188 more) with PBI/APBI (OR 5.07, 95% CI 3.81 to 6.74; 2 studies, 3011 participants; moderate-certainty evidence). The use of PBI/APBI probably makes little difference (1/1000 less, 95% CI 6 fewer to 3 more) to cause-specific survival (HR 1.06, 95% CI 0.83 to 1.36; 7 studies, 9865 participants; moderate-certainty evidence). We found the use of PBI/APBI compared with WBRT probably makes little or no difference (1/1000 fewer (95% CI 4 fewer to 6 more)) to distant metastasis-free survival (HR 0.95, 95% CI 0.80 to 1.13; 7 studies, 11,033 participants; moderate-certainty evidence). We found the use of PBI/APBI in comparison with WBRT makes little or no difference (2/1000 fewer, 95% CI 20 fewer to 20 more) to mastectomy rates (OR 0.98, 95% CI 0.78 to 1.23; 3 studies, 3740 participants, high-certainty evidence). It appeared that local recurrence-free survival is probably worse with PBI/APBI; however, the difference was small and nearly all women remain free of local recurrence. Overall survival is similar with PBI/APBI and WBRT, and we found little to no difference in other oncological outcomes. Some late effects (subcutaneous fibrosis) may be worse with PBI/APBI and its use is probably associated with worse cosmetic outcomes. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver PBI/APBI. We await completion of ongoing trials.

Abstract GS2-04: A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01)

Abstract Background: Wholebreast irradiation (WBI) after breast conserving surgery for DCIS reduces therisk of local recurrence including invasive recurrence. The objective of BIG3-07/TROG 07.01 is to test radiation dose escalation to the tumor bed (tumorbed boost) and fractionation sensitivity of whole breast irradiation (WBI) inpatients with non-low risk DCIS treated with breast conserving therapy. Methods: BIG3-07/TROG 07.01 is an international, multicenter, randomized, controlled, phase 3 trial. Eligible women were ≥18 years ofage with completely resected non-low risk DCIS defined as age &amp;lt;50 years orage ≥50 years plus at least one of the risk factors for local recurrence (palpable tumor,multifocal disease, tumor size ≥ 1.5cm, intermediate or high nuclear grade, central necrosis, comedo histologyand/or surgical margin &amp;lt;10 mm). Patients were randomized to have tumor bedboost (16 Gy in 8 daily fractions) or no boost following conventional WBI (50Gy in 25 daily fractions) or hypofractionated WBI (42.5 Gy in 16 dailyfractions) in one of three randomization categories selected by centers priorto study activation. Randomization A was a 4-arm randomization of no boost vs. boostfollowing conventional WBI vs. hypofractionated WBI. Patients in RandomizationB and Randomization C were assigned no boost or boost following conventional WBIand hypofractionated WBI, respectively. The primary endpoint was time to localrecurrence, analyzed by intention to treat. The trial was designed to detect a3% difference in 5-year free-from- local recurrence rates between the no boostand boost groups (93% vs 96%; hazard ratio, 0.56) with 90% power and 2-sidedalpha level of 5%. The primary effect of boost was assessed on all randomizedpatients. The secondary effect of WBI dose-fractionation and the interactionbetween boost and WBI dose-fractionation were assessed on patients in RandomizationA and additionally on all patients. Results: BetweenJune 2007 and June 2014, 1608 patients were randomized to have no boost (805patients) or boost (803 patients) after WBI. Conventional WBI was given in 831 patients(no boost in 416 patients; boost in 415 patients). Hypofractionated WBI wasgiven in 777 patients (no boost in 389 patients; boost in 388 patients). Adjuvantendocrine therapy was planned in 106 patients (13%) in the no boost group and105 patients (13%) in the boost group. Median follow-up was 6.6 years. The 5-yearfree-from- local recurrence rates were 93% in the no boost group and 97% in theboost group (hazard ratio, 0.47; 95% confidence interval [CI], 0.31 to 0.72;P&amp;lt;0.001). Forty-four percent and 45% of LRs were invasive in the no boostgroup and boost group, respectively. The effect of boost did not vary significantlyby age, tumor size, nuclear grade, surgical margin or endocrine therapy. Therewere no significant differences in the 5-year free-from- local recurrence ratesbetween the conventional WBI group and hypofractionated WBI group inRandomization A (94% vs. 94%, P=0.84) and in all randomized patients (95% vs.95%, P=0.89). The test for interaction between boost and dose-fractionation wasnot significant in Randomization A or in all randomized patients (both P=0.89).The rates of grade ≥2 breastpain (12% vs. 16%, P=0.84) and skin and subcutaneous tissue fibrosis (6% vs.15%, P=0.14) did not differ significantly between the groups. Conclusions: Inwomen with non-low risk DCIS treatedwith breast conserving surgery, the addition of tumor bed boost followingconventional or hypofractionated WBI reduced local recurrence rates. There wasno difference in local recurrence rates between conventional WBI andhypofractionated WBI. (Registered with ClinicalTrials.gov, NCT00470236.) Citation Format: Boon Hui Chua, Emma Link, Ian Kunkler, Ivo Olivotto, Antonia Helen Westenberg, Timothy Whelan, Guenther Gruber, Breast International Group (BIG)-aisbl, Trans Tasman Radiation Oncology Group, Scottish Cancer Trials Breast Group, Canadian Cancer Trials Group, European Organization for Research and Treatment of Cancer, International Breast Cancer Study Group, Cancer Trials Ireland. A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-04.

Examining the Financial Impact of Altered Fractionation in Breast Cancer: An Analysis Using Time-Driven Activity-Based Costing

PurposeValue-based care is increasingly informing treatment decisions in radiation oncology. Although reimbursement differences have been examined for accelerated whole breast irradiation (AWBI) and conventional whole breast irradiation (CWBI), the cost of care delivery is poorly understood. This article describes our experience evaluating costs for altered fractionation in early-stage breast cancer using a time-driven activity-based costing (TDABC) model. Methods and MaterialsProcess maps were developed for 2 treatment regimens, AWBI (42.5 Gy in 16 fractions + 10 Gy in 4 fractions boost) and CWBI (50 Gy in 25 fractions + 10 Gy in 5 fractions boost). Cost was determined based on aggregate cost of personnel, materials, equipment, space, and utilities per unit time and based on the relative proportion of capacity used. The total reimbursement for each regimen was calculated as the aggregate of all billable events during a course of radiation therapy, based on the 2019 Centers for Medicare & Medicaid Services physician fee schedule database. ResultsThe total cost of delivering courses of AWBI and CWBI was $6965 and $9267, respectively, a difference of $2302 (25%). Eighty-six percent of this difference was related to a lower cost of delivering daily treatments. The total reimbursement for AWBI or CWBI was $9665 or $12,908, respectively, a difference of $3243 (25%). Overall, 55% to 60% of total costs were related to personnel, with the remainder related to materials, utilities, space, and equipment. ConclusionsThis analysis shows how TDABC can be used to evaluate resource requirements for different radiation therapy fractionation schedules. We found a substantially lower cost for AWBI compared with CWBI, primarily resulting from fewer daily treatments. As the emphasis in health care shifts toward value-based care, TDABC can help identify opportunities to reduce costs and increase clinical efficiency.

Accelerated Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer; ARandomized Phase III Clinical Trial

To compare the cosmetic outcome and acute cutaneous, cardiac, and pulmonary toxicity profile of accelerated hypofractionated and conventional whole breast radiotherapy (WBRT).This was a blocked randomized, clinical trial on women with early-stage node-negative invasive breast cancer after breast conservation surgery (BCS) with clear margins randomly assigned to receive WBRT either at a conventional dose of 50.0 grays (Gy) in 25 fractions (the conventional group) or at a dose of 42.5 Gy in 16 fractions (the hypofractionated group). Boost irradiation was permitted in both groups. Data were analyzed by SPSS V21.0 using Mann–Whitney U, independent-samples t- and Chi-Square/Fisher's exact tests at the level of P≤0.05.The median follows up was 16 months. Forty-one patients in the conventional WBRT arm and 45 patients in the hypofractionated WBRT group were enrolled. No significant difference was observed in terms of left and right ventricle systolic dysfunction and diastolic dysfunction. Pulmonary function tests after 6 and 12 months follow up, were comparable in both groups (P=0.2). Skin toxicity during and after treatment was acceptable in both groups. Breast size change in the conventional and the hypofractionated WBRT groups was 14.3% and 7.1%, respectively (P=0.6). Excellent or good cosmetic outcome was similar in both groups.The results of our study support the use of accelerated hypofractionated WBRT in women with invasive breast cancer less than five cm and node-negative after breast-conserving surgery, which provides a more convenient shorter course of radiotherapy with a comparable cosmetic outcome and cutaneous, cardiac, and pulmonary toxicity profile.

Fatigue following radiotherapy of low-risk early breast cancer \u2013 a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419)

BackgroundFatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients.MethodsThis trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale.DiscussionThe present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance.Trial registrationThe study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. “Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)”.Study statusOngoing study. Start of recruitment was December 2019.

Acute Toxicity and Quality of Life of Hypofractionated Radiation Therapy for Breast Cancer

To assess the acute toxicity and quality of life (QOL) of hypofractionation compared with conventional fractionation for whole breast irradiation (WBI) after breast-conserving surgery. Women with node-negative breast cancer who had undergone breast-conserving surgery with clear margins were randomly assigned to conventional WBI of 5000 cGy in 25 fractions over 35 days or hypofractionated WBI of 4256 cGy in 16 fractions over 22 days. Acute skin toxicity and QOL were assessed at baseline and 2, 4, 6, and 8 weeks from the start of treatment for a subgroup of patients. QOL was assessed at baseline and 4 weeks posttreatment for all patients. In the acute toxicity substudy, repeated measures modeling was used to investigate treatment by time interactions over the 8-week period for acute toxicity and QOL mean change score. QOL mean change score from baseline to 4 weeks posttreatment was compared for all patients. In the acute toxicity substudy, 161 patients participated. In the main trial, 1152 patients participated. Acute skin toxicity was initially similar between groups but was less with hypofractionation compared with conventional fractionation toward the end of the 8-week period (P < .001). QOL at 6 weeks from the start of treatment was improved with hypofractionation for the skin side effects, breast side effects, fatigue, attractiveness, and convenience domains (all P < .05). In the main trial, hypofractionation resulted in improved overall QOL and QOL attributed to skin side effects, breast side effects, and attractiveness (all P < .01). Hypofractionated WBI compared with conventional WBI resulted in less acute toxicity and improved QOL. This further supports the benefits of hypofractionation.

Acute radiation-induced skin toxicity in hypofractionated vs. conventional whole-breast irradiation: An objective, randomized multicenter assessment using spectrophotometry

PurposeRadiation dermatitis represents one of the most frequent side effects in breast cancer patients undergoing adjuvant whole-breast irradiation (WBI). Whether hypofractionated WBI induces comparable or less acute radiation-induced skin reactions than conventional WBI is still not fully clarified, as randomized evidence and objective assessments are limited. The aim of this study was to objectively determine frequency and severity of acute radiation-induced skin reactions during hypofractionated vs. conventionally fractionated adjuvant WBI. MethodsIn this randomized multicenter study, a total of 140 breast cancer patients underwent either hypofractionated or conventional WBI following breast-preserving surgery. Maximum radiation dermatitis severity was assessed at completion and during follow-up by physician-assessed CTCAE v4.03 and the patient-reported RISRAS scale. Additionally, photospectrometric skin readings were performed to objectify skin color differences between both treatment arms. ResultsRadiation dermatitis severity was significantly lower in patients receiving hypofractionation compared with conventional fractionation (mean 1.05 vs. 1.43, p = .024). Grade 0 radiation dermatitis occurred in 21.43% vs. 4.28%, grade ≥2 in 27.14% vs. 42.91% and grade ≥3 in 0% vs. 4.34% of patients following hypofractionated and conventional WBI, respectively. Objective photospectrometric measurements (n = 4200) showed both decreased erythema severity (p = .008) and hyperpigmentation (p = .002) in the hypofractionation arm. Patients allocated to hypofractionated WBI also reported less pain (p = .006), less hyperpigmentation (p = <0.001) and less limitations of day-to-day activities (p = <0.001). ConclusionPhysician and patient-assessed toxicity scorings as well as objective photospectrometric skin measurements revealed that hypofractionated WBI yielded lower rates and severity of acute radiation-induced skin toxicity.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast

PurposeTo assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. Materials and methodsBaseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/− TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. Results1608 women were enrolled from 11 countries between 2007 and 2014. 85–90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). ConclusionsCosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

Clinical observation of early-stage breast cancer after breast-conserving surgery with hypofractionated radiotherapy

Objective To observe the long-term effect, adverse reaction and cosmetic outcome of early-stage breast cancer with hypofractionated whole-breast irradiation (HF-WBI) after breast-conserving surgery. Methods A total of 206 patients with stage 0-Ⅱ breast cancer after breast-conserving surgery were included in Shandong Cancer Hospital Affiliated to Shandong University from May 2014 to August 2017. According to radiotherapy fraction, patients were divided into HF-WBI group and conventional whole-breast irradiation (CF-WBI) group. In HF-WBI group, 116 patients received whole-breast radiation to 42.56 Gy in 16 fractions followed by tumor bed boost of 9 Gy in 3 fractions or 10 Gy in 5 fractions. In CF-WBI group, 90 patients received whole breast radiation to 50 Gy in 25 fractions followed by tumor bed boost of 10 Gy in 5 fractions. The 2-year local recurrence rate, 2-year mortality rate, acute adverse reaction, late adverse reaction and cosmetic outcome of the two groups were analyzed. Results The 2-year local recurrence rates of HF-WBI group and CF-WBI group were 0.86% (1/116) and 2.22% (2/90) respectively, and there was no significant difference between the two groups (χ2=0.049, P=0.824). The 2-year mortality rates of the two groups were 0.86% (1/116) and 0 (0/90) respectively, and there was no significant difference (P>0.999). There were 108 cases (93.1%) in HF-WBI group and 84 cases (93.3%) in CF-WBI group with grade 0-1 acute dermatitis, and 8 cases (6.9%) and 6 cases (6.7%) with grade 2-3 respectively, with no statistically significant difference (χ2=0.004, P=0.948). There were 97 cases (83.6%) in HF-WBI group and 79 cases (87.8%) in CF-WBI group with grade 0-1 bone marrow suppression, and 19 cases (16.4%) and 11 cases (12.2%) with grade 2-4 respectively, with no statistically significant difference (χ2=0.704, P=0.401). In the two groups, there were 1 case (0.9%) and 3 cases (3.3%) with grade 1-2 radiation pneumonitis, and 115 cases (99.1%) and 87 cases (96.7%) with no radiation pneumonitis respectively, and the difference was not statistically significant (χ2=1.626, P=0.202). There was 1 case (0.9%, 1.1%) with grade 1 breast edema in each group, and 115 cases (99.1%) and 89 cases (98.9%) did not occur breast edema, with no statistically significant difference (χ2=0.033, P=0.857). In the late adverse reactions, there were 5 cases (4.3%) and 3 cases (3.3%) with skin pigmentation in HF-WBI group and CF-WBI group respectively. There were 2 cases (1.7%, 2.2%) with grade 1 subcutaneous tissue fibrosis in each group, and there were 1 case (0.8%) and 2 cases (2.2%) with grade 1 pulmonary fibrosis respectively. The differences between the two groups were not statistically significant (χ2=0.000, P>0.999; χ2=0.000, P>0.999; χ2=0.049, P=0.824). The 6-month, 1-year and 2-year cosmetic outcome good rates in HF-WBI and CF-WBI group were 96.5% (111/115) and 93.3% (84/90), 92.1% (105/114) and 90.0% (81/90), 91.4% (53/58) and 87.2% (41/47) respectively. The differences between the two groups were not statistically significant (χ2=0.526, P=0.468; χ2=0.277, P=0.599; χ2=0.476, P=0.490). The whole course of radiotherapy time in HF-WBI group was 25 days or 29 days, which was significantly shorter than the 40 days of CF-WBI group. Conclusion HF-WBI after breast-conserving surgery has the similar long-term effect, acute and late adverse reaction and cosmetic outcome compared with CF-WBI, and the treatment time is significantly shorter. It can be further promoted as the optimal adjuvant radiotherapy for early-stage breast cancer after breast-conserving surgery. Key words: Breast neoplasms; Radiotherapy; Treatment outcome

The prognosis comparison of different molecular subtypes of breast tumors after radiotherapy and the intrinsic reasons for their distinct radiosensitivity.

Radiotherapy can increase the cell cycle arrest that promotes apoptosis, reduces the risk of tumor recurrence and has become an irreplaceable component of systematic treatment for patients with breast cancer. Substantial advances in precise radiotherapy unequivocally indicate that the benefits of radiotherapy vary depending on intrinsic subtypes of the disease; luminal A breast cancer has the highest benefit whereas human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) are affected to a lesser extent irrespective of the selection of radiotherapy strategies, such as conventional whole-breast irradiation (CWBI), accelerated partial-breast irradiation (APBI), and hypofractionated whole-breast irradiation (HWBI). The benefit disparity correlates with the differential invasiveness, malignance, and radiosensitivity of the subtypes. A combination of a number of molecular mechanisms leads to the strong radioresistant profile of HER2-positive breast cancer, and sensitization to irradiation can be induced by multiple drugs or compounds in luminal disease and TNBC. In this review, we aimed to summarize the prognostic differences between various subtypes of breast tumors after CWBI, APBI, and HWBI, the potential reasons for drug-enhanced radiosensitivity in luminal breast tumors and TNBC, and the robust radioresistance of HER2-positive cancer.

Abstract GS4-04: Primary results of NSABP B-39/RTOG 0413 (NRG Oncology): A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer

Abstract Background: Conventional WBI after lumpectomy for early-stage breast cancer decreases ipsilateral breast tumor recurrence (IBTR), yielding comparable results to mastectomy. Accelerated PBI appears effective in reducing IBTR by treating only the tumor bed area. As the majority of IBTR occur at or in the vicinity of the tumor bed, we hypothesized that PBI would be as effective as WBI in controlling IBTR. The primary aim of NSABP B-39/RTOG 0413 was to determine if PBI provides equivalent local tumor control post lumpectomy compared to WBI in pts with early-stage breast cancer. The equivalency test was based on a 50% margin of increase in the hazard ratio (HR=1.5). Secondary endpoints included: overall survival (OS), recurrence-free interval (RFI), distant disease-free interval (DDFI), and toxicity. Methods: Eligible pts had lumpectomy with histologically-free margins and 0-3 positive axillary nodes. Pts were stratified by stage, menopausal status, hormone receptor status, and intent to receive chemotherapy and then randomized to PBI or WBI. PBI was 10 fractions of 3.4-3.85 Gy, given twice daily with either brachytherapy or 3D external beam radiation. WBI was 50 Gy in 2 Gy fractions given daily with a sequential boost to the surgical cavity. Follow-up was every 6 mos for 5 yrs and then annually. All analyses were by intent-to-treat. Results: From 3-21-05 to 4-16-13, 4216 pts were randomized: 2107 PBI; 2109 WBI. 61% were postmenopausal; 81% were hormone receptor-positive; 29% intended to receive chemotherapy. Stage distribution was: DCIS, 24%; invasive pN0, 65%; invasive pN1, 10%. As of 7-31-18, median follow-up was 10.2 yrs. There were 161 IBTRs as first events: 90 PBI v 71 WBI (HR 1.22; 90%CI 0.94-1.58). Per protocol-defined margin, to declare PBI and WBI equivalent regarding IBTR risk, the 90% CI for the observed HR had to lie entirely between 0.667 and 1.5. The percent of pts IBTR-free at 10 yrs was 95.2% PBI v 95.9% WBI. A statistically significant difference in the 10-yr RFI rate favored WBI (91.9% PBI v 93.4% WBI; HR 1.32; 95%CI 1.04-1.68; p=0.02). No statistically significant differences existed between PBI and WBI in DDFI (HR 1.31; 95%CI 0.91-1.91; p=0.15), OS (HR 1.10; 95%CI 0.90-1.35; p=0.35), or DFS (HR 1.12; 95%CI 0.98-1.29; p=0.11). Grade 3 toxicity was 9.6% PBI v 7.1% WBI, and grade 4-5 toxicity was 0.5% v 0.3%, respectively. Discussion: PBI did not meet the criteria for equivalence to WBI in controlling IBTR based on the upper limit of the hazard ratio confidence interval. However, the absolute difference in 10-yr rate of IBTR was &amp;lt;1% (4.8% PBI v 4.1% WBI). The risk of an RFI event was statistically significantly higher for PBI compared to WBI, but the absolute difference in 10-yr RFI rate was also small (8.1% PBI v 6.6% WBI). DDFI, OS, and DFS were not statistically different for PBI v WBI. Grade 3-5 toxicities, although low, were more common for PBI than WBI. The trial population was heterogeneous, ranging from Stage 0-2 breast cancer, and outcome by risk categories are being analyzed. Support: U10CA180868, -180822, UG1CA189867. Citation Format: Vicini FA, Cecchini RS, White JR, Julian TB, Arthur DW, Rabinovitch RA, Kuske RR, Parda DS, Ganz PA, Scheier MF, Winter KA, Paik S, Kuerer HM, Vallow LA, Pierce LJ, Mamounas EP, Costantino JP, Bear HD, Germaine I, Gustafson G, Grossheim L, Petersen IA, Hudes RS, Curran, Jr. WJ, Wolmark N. Primary results of NSABP B-39/RTOG 0413 (NRG Oncology): A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-04.

Robotic Stereotactic Boost in Early Breast Cancer, a Phase 2 Trial

To evaluate the feasibility and toxicity of a single-fraction 8-Gy stereotactic boost after whole-breast irradiation in early breast cancer. The primary aim of this phase 2 study was to evaluate cutaneous breast toxicity using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) 3months after the boost. Secondary objectives were local control, survival, and patient-reported quality of life using the European Organisation for Research and Treatment of Cancer QLQ-C30 and breast-specific European Organisation for Research and Treatment of Cancer QLQ-BR 23 questionnaires. Patients with invasive ductal or lobular pT1-2 breast cancer treated with lumpectomy with clear margins and pN0 were included. Patients requiring chemotherapy were excluded. Twenty-eight eligible patients received the planned boost, and 26 had hormonal therapy. The procedure was technically successful without procedural complications. A median of 3 fiducials were tracked, and 115 beams were used. There were 22 acute grade 1 breast skin toxicities, including fibrosis, pain, erythema, or pigmentation. There were 2 acute grade 2 erythemas. Median skin boost dose was inversely correlated with acute skin toxicity (P=.028). QLQ-C30 scores revealed acute dyspnea and arm symptoms without correlation to the boost dose. Breast symptom QLQ-BR23 scores did not deteriorate, although upset with hair loss and systemic side effects of hormonal therapy were observed. After a median follow-up of 38months, 1 patient had in-boost-field relapse, and there were 5 late grade 1 and 1 grade 2 skin toxicities. Single-fraction stereotactic boost after conventional whole-breast irradiation in early breast cancer is feasible with minor toxicities. Quality of life and specific breast items showed excellent patient acceptance.

Use of hypofractionated radiotherapy for early stage breast cancer after implementation of evidence-based clinical guidelines.

6593Background: Evidence-based guidelines have endorsed use of hypofractionated whole breast irradiation (WBI), a shorter course regimen delivered over 3-4 weeks instead of conventional WBI over 5-...

Definitive Radiotherapy With SBRT or IMRT Boost for Breast Cancer: Excellent Local Control and Cosmetic Outcome.

The gold standard for breast cancer treatment is surgery, but many women may desire to avoid surgery if possible. The purpose of this study was to evaluate whether breast cancer could be cured with modern sophisticated radiation techniques with good cosmetic outcome. We have treated 18 patients with operable breast cancer by conventional whole-breast irradiation followed by stereotactic body radiotherapy (primary tumor only) or intensity-modulated radiotherapy (tumor plus axillary nodes) boost. The planned doses were 50 Gy in 25 fractions, 18 to 25.5 Gy in 3 fractions, and 20 Gy in 8 fractions, respectively, for the 3 modalities. Stereotactic body radiotherapy was delivered with 7 to 9 coplanar and noncoplanar fixed beams, and intensity-modulated radiotherapy was given by tomotherapy. Chemotherapy and/or hormone therapy was used depending on the stage and receptor status. In 9 recent patients, hydrogen peroxide was intratumorally injected twice a week before whole-breast irradiation. All treatments were well tolerable and there were no grade ≥3 toxicities. With a median follow-up period of 35 months (range, 8-120 months), only 1 patient developed local recurrence and 2 patients developed distant metastasis. Overall survival, progression-free survival, and local control rates were 93%, 85%, and 92%, respectively, at 3 years. In 50% of the patients, the irradiated breast became better rounded, and the position of the nipple of the irradiated breast became ≥1 cm higher compared to that of the unirradiated breast. Thus, the treated breasts may be more aesthetically favorable than before irradiation in these patients. This may become a treatment option for patients with operable breast cancer.

Reconstruction of Catheter Paths for High Dose Rate Breast Brachytherapy: A Phantom Model

Accelerated partial breast irradiation (APBI) is performed in early-stage breast cancer patients after lumpectomy, and treats the surgical bed rather than the entire breast. The treatment time for APBI is one week or less compared to conventional whole-breast irradiation where the treatment time ranges from three to seven weeks. One treatment modality in APBI is multi-catheter interstitial brachytherapy (MIB); however, MIB is a technically challenging procedure because knowledge of both the positioning and the spacing of the inserted catheters is crucial for achieving adequate dosimetric coverage of the lumpectomy cavity. Conventionally, ultrasound, fluoroscopy, or computed tomography (CT) are used to determine the catheter positioning and spacing, but these are either difficult to interpret, or they expose the patient to radiation. We investigated the use of electromagnetic reconstruction (EMR) for this purpose. This study compares the catheter paths recorded with EMR with catheter paths modeled on CT. Two anthropomorphic plastic phantoms were made with simulated tumour beds that could be seen with both ultrasound and CT. In this experiment, thirteen catheters were inserted into the phantoms using ultrasound guidance. EMR was performed by pulling through each catheter an electromagnetic enabled sensor and collecting position information. The position information was then used to reconstruct the catheter path based on a least-squares polynomial fit using the free and open-source 3D Slicer (www.slicer.org) platform. The sensor transmitted position information to a navigation computer using the PLUS toolkit software. CT images were collected and aligned with the reconstructions to conduct an analysis of accuracy. The Vascular Modeling Toolkit software was used to compare the EM-generated paths to the CT generated paths. The paths were then aligned and measured at regular positions along the phantom. The aim of the study was to be accurate within 0.68mm, which is the axial resolution of the CT scanner. The thirteen catheters modeled with EMR were all aligned with the paths imaged on the CT scan. The mean distance between the catheter paths modeled on the CT scan and EMR was 0.38 +/- 0.13 mm, which is lower than the axial resolution of the CT scanner. The use of EMR was accurate and reproducible for determining the paths of the implanted catheters. The results of this phantom experiment suggest that using EMR is a promising tool that is consistent and reproducible. EMR’s ability to accurately determine catheter positioning and spacing in three dimensions may be useful in facilitating planning. Further research is being conducted to use this tool in patients and in clinical trials.

Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial

We previously confirmed the non-inferiority of accelerated partial breast irradiation (APBI) with interstitial brachytherapy in terms of local control and overall survival compared with whole-breast irradiation for patients with early-stage breast cancer who underwent breast-conserving surgery in a phase 3 randomised trial. Here, we present the 5-year late side-effects and cosmetic results of the trial. We did this randomised, controlled, phase 3 trial at 16 centres in seven European countries. Women aged 40 years or older with stage 0-IIA breast cancer who underwent breast-conserving surgery with microscopically clear resection margins of at least 2 mm were randomly assigned 1:1, via an online interface, to receive either whole-breast irradiation of 50 Gy with a tumour-bed boost of 10 Gy or APBI with interstitial brachytherapy. Randomisation was stratified by study centre, menopausal status, and tumour type (invasive carcinoma vs ductal carcinoma in situ), with a block size of ten, according to an automated dynamic algorithm. Patients and investigators were not masked to treatment allocation. The primary endpoint of our initial analysis was ipsilateral local recurrence; here, we report the secondary endpoints of late side-effects and cosmesis. We analysed physician-scored late toxicities and patient-scored and physician-scored cosmetic results from the date of breast-conserving surgery to the date of onset of event. Analysis was done according to treatment received (as-treated population). This trial is registered with ClinicalTrials.gov, number NCT00402519. Between April 20, 2004, and July 30, 2009, we randomly assigned 1328 women to receive either whole-breast irradiation (n=673) or APBI with interstitial brachytherapy (n=655); 1184 patients comprised the as-treated population (551 in the whole-breast irradiation group and 633 in the APBI group). At a median follow-up of 6·6 years (IQR 5·8-7·6), no patients had any grade 4 toxities, and three (<1%) of 484 patients in the APBI group and seven (2%) of 393 in the whole-breast irradiation group had grade 3 late skin toxicity (p=0·16). No patients in the APBI group and two (<1%) in the whole-breast irradiation group developed grade 3 late subcutaneous tissue toxicity (p=0·10). The cumulative incidence of any late side-effect of grade 2 or worse at 5 years was 27·0% (95% CI 23·0-30·9) in the whole-breast irradiation group versus 23·3% (19·9-26·8) in the APBI group (p=0·12). The cumulative incidence of grade 2-3 late skin toxicity at 5 years was 10·7% (95% CI 8·0-13·4) in the whole-breast irradiation group versus 6·9% (4·8-9·0) in the APBI group (difference -3·8%, 95% CI -7·2 to 0·4; p=0·020). The cumulative risk of grade 2-3 late subcutaneous tissue side-effects at 5 years was 9·7% (95% CI 7·1-12·3) in the whole-breast irradiation group versus 12·0% (9·4-14·7) in the APBI group (difference 2·4%; 95% CI -1·4 to 6·1; p=0·28). The cumulative incidence of grade 2-3 breast pain was 11·9% (95% CI 9·0-14·7) after whole-breast irradiation versus 8·4% (6·1-10·6) after APBI (difference -3·5%; 95% CI -7·1 to 0·1; p=0·074). At 5 years' follow-up, according to the patients' view, 413 (91%) of 454 patients had excellent to good cosmetic results in the whole-breast irradiation group versus 498 (92%) of 541 patients in the APBI group (p=0·62); when judged by the physicians, 408 (90%) of 454 patients and 503 (93%) of 542 patients, respectively, had excellent to good cosmetic results (p=0·12). No treatment-related deaths occurred, but six (15%) of 41 patients (three in each group) died from breast cancer, and 35 (85%) deaths (21 in the whole-breast irradiation group and 14 in the APBI group) were unrelated. 5-year toxicity profiles and cosmetic results were similar in patients treated with breast-conserving surgery followed by either APBI with interstitial brachytherapy or conventional whole-breast irradiation, with significantly fewer grade 2-3 late skin side-effects after APBI with interstitial brachytherapy. These findings provide further clinical evidence for the routine use of interstitial multicatheter brachytherapy-based APBI in the treatment of patients with low-risk breast cancer who opt for breast conservation. German Cancer Aid.