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Background: The effectiveness and safety of moderately hypofractionated radiotherapy (HFRT) in patients undergoing breast-conserving surgery (BCS) has been demonstrated in several pivotal randomized trials. However, the feasibility of applying simultaneous integrated boost (SIB) to the tumor bed and regional node irradiation (RNI) using modern radiotherapy techniques with HFRT needs further evaluation. Methods: This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to determine the non-inferiority of HFRT combined with SIB (HFRTsib) compared with conventional fractionated radiotherapy with sequential boost (CFRTseq) in terms of five-year locoregional control rate in breast cancer patients undergoing upfront BCS. A total of 2904 participants will be recruited and randomized in a 1:1 ratio into the HFRTsib and CFRTseq groups. All patients will receive whole breast irradiation, and those with positive axillary nodes will receive additional RNI, including internal mammary irradiation. The prescribed dose for the HFRTsib group will be 40 Gy in 15 fractions, combined with a SIB of 48 Gy in 15 fractions to the tumor bed. The CFRTseq group will receive 50 Gy in 25 fractions, with a sequential boost of 10 Gy in 5 fractions to the tumor bed. Discussion: This trial intends to assess the effectiveness and safety of SIB combined with HFRT in early breast cancer patients following BCS. The primary endpoint is locoregional control, and the results of this trial are expected to offer crucial evidence for utilizing HFRT in breast cancer patients after BCS. Trial registration: This trial was registered at ClincalTrials.gov (NCT04025164) on July 18, 2019. [ABSTRACT FROM AUTHOR]

The addition of a boost to the lumpectomy bed after whole-breast (WB) radiotherapy plays a key role in the treatment of patients with breast cancer (BC). The clinical benefits of a boost with high-dose-rate brachytherapy (HDR-BT) after conventional fractionation is supported by a large body of evidence. However, few studies have described its outcomes after a hypofractionated scheme. We included all patients treated with adjuvant WB-IMRT in 15 sessions followed by a single-session HDR-BT boost with local anesthesia on an outpatient basis. Between 2009 and 2017, 638 patients with early-stage BC were treated according to the aforementioned protocol after breast-conserving surgery. Median follow-up was 6 years (4–11). Despite the low incidence of side effects and their slightness, we did identify an impact of breast volume on the risk of acute radiodermatitis, fibrosis, pain and edema. However, we did not identify any relationship between the volume in cubic centimeters of the BT-implant with acute or long-term side effects. 2.2% patients had an actual local relapse, 2.4% a 2nd primary in the same breast and 2.39% were diagnosed with contralateral BC. Event-free survival at 11 years was 85.5% with an overall survival of 95.7%. Adjuvant hypofractionated whole-breast IMRT followed by a single dose HDR-BT boost has a low incidence of acute and chronic toxicity and excellent oncological outcomes. However, it may be worthwhile to intensify self-care protocols and surveillance in women with large breasts who may be at increased risk of side effects. [ABSTRACT FROM AUTHOR]

This study investigated the cosmetic degradation and toxicity for an accelerated partial breast irradiation (APBI) prescription delivered in 5 fractions over 1 week and compared the outcomes with those of whole breast irradiation (WBI). The trial was a multicenter, single-arm, phase 2 prospective cohort study. Eligible women 50 years of age or older with estrogen receptor–positive and human epidermal growth factor receptor 2–negative invasive ductal carcinoma or ductal carcinoma in situ after breast-conserving surgery received 27 Gy in 5 daily fractions of APBI. The primary endpoint was noninferiority of 2-year cosmesis using the RAPID trial's WBI arm as the control arm. A global consensus cosmetic score using a European Organisation for Research and Treatment of Cancer rating scale score of excellent, good, fair, or poor for each patient at baseline and 2 years was generated by a panel of 5 radiation oncologists using photographs of treated and untreated breasts. From 2016 to 2019, 298 eligible women were enrolled. By the 2-year follow-up, 76 patients had been lost or withdrawn and 3 had died, resulting in 219 patients available for complete, 2-year photographic cosmetic evaluation. The median follow-up for all participants was 4.7 years (IQR, 3.8-5.5 years). No patient had a fair or poor cosmetic score at the 2-year evaluation. Cosmesis was better or unchanged for 97% of patients and worse for 3% (excellent to good), and no cosmetic failures occurred. The confidence intervals were 0.88 (0.86-0.90) and 1.00 (0.99-1.00) for the RAPID and ACCEL trials, respectively. Cosmetic degradation with 5 daily treatments of the ACCEL trial's APBI intervention is noninferior to the WBI arm of the RAPID trial. [ABSTRACT FROM AUTHOR]

Whole breast irradiation after breast‐conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery. Accelerated partial breast irradiation (APBI) as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research. APBI is characterised by simple high‐dose local irradiation of the tumour bed in a short time, thus improving convenience for patients and saving costs. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI. [ABSTRACT FROM AUTHOR]

Background: This study investigated the differences in target volumes between preoperative magnetic resonance imaging (MRIpre) and postoperative MRI (MRIpost) for breast radiotherapy after breast‐conserving surgery (BCS) using deformable image registration (DIR). Methods and Materials: Seventeen eligible patients who underwent whole‐breast irradiation in the prone position after BCS were enrolled. On MRIpre, the gross tumor volume (GTV) was delineated as GTVpre, which was then expanded by 10 mm to represent the preoperative lumpectomy cavity (LC), denoted as LCpre. The LC was expanded to the clinical target volume (CTV) and planning target volume (PTV) on the MRIpre and MRIpost, denoted as CTVpre, CTVpost, PTVpre, and PTVpost, respectively. The MIM software system was used to register the MRIpre and MRIpost using DIR. Differences were evaluated regarding target volume, distance between the centers of mass (dCOM), conformity index (CI), and degree of inclusion (DI). The relationship between CILC/CIPTV and the clinical factors was also assessed. Results: Significant differences were observed in LC and PTV volumes between MRIpre and MRIpost (p < 0.0001). LCpre was 0.85 cm3 larger than LCpost, while PTVpre was 29.38 cm3 smaller than PTVpost. The dCOM between LCpre and LCpost was 1.371 cm, while that between PTVpre and PTVpost reduced to 1.348 cm. There were statistically significant increases in CI and DI for LCpost–LCpre and PTVpost–PTVpre (CI = 0.221, 0.470; DI = 0.472, 0.635). No obvious linear correlations (p > 0.05) were found between CI and GTV, primary tumor volume‐to‐breast volume ratio, distance from the primary tumor to the nipple and chest wall, and body mass index. Conclusions: Despite using DIR technology, the spatial correspondence of target volumes between MRIpre and MRIpost was suboptimal. Therefore, relying solely on preoperative diagnostic MRI with DIR for postoperative LC delineation is not recommended. [ABSTRACT FROM AUTHOR]

Assess the local recurrence rate and global survival rate among women diagnosed with breast cancer who underwent intraoperative electron radiotherapy (IOERT) between 2007 and 2017, in a single private healthcare setting in Belo Horizonte, Brazil. This is a retrospective study based on medical records about the outcomes of patients submitted to breast-conserving surgery followed by IOERT. The collected variables included the patient's profile and tumor features, IOERT isodose, and outcomes. The quantitative data were presented in tables of frequency. The survival curves were created with the Kaplan-Meier method. In all tests, the adopted relevance level was 5%. The analyses were carried out with SPSS version 25.0. The samples consisted of 78 patients, among which a total of 14 (17.9%) recurrences were observed. The median time of recurrence was 49 months after the IOERT was performed. Of the 78 patients analyzed, 13 (16.7%) died, 5 (6.4%) of which were due to breast cancer. The global survival rate in 5 years was 94.9% and 90.4% in 10 years. The local recurrence rate in 5 years was 89.7% and 86.4% in 10 years. Our findings revealed a higher local recurrence rate than the literature data. However, our results also showed that patients classified as low-risk had an overall survival of 5 and 10 years similar to other studies in the literature, reaffirming that low-risk women can benefit from IOERT. Given this finding, it is reaffirmed that rigorous eligibility criteria for IOERT are critical to reducing local recurrence. [ABSTRACT FROM AUTHOR]

For second ipsilateral breast tumor event (2nd IBTE), second conservative treatment (2nd CT) combining lumpectomy plus accelerated partial breast reirradiation (APBrI) represents a curative option. The aim of this study was to analyze oncological prognostic factors for patients with a 2nd IBTE treated with 2nd CT. An analysis of clinical practices was conducted across 7 academic hospitals/cancer centers in 6 European countries based on the GEC-ESTRO database. Patients presenting a 2nd IBTE occurring after conservative surgery (lumpectomy + axillary evaluation) and irradiation performed for the primary tumor underwent a 2nd CT with brachytherapy-based APBrI. The main outcome was 5-year cumulative incidence (CI) rate of second local relapse. All analyzed patients were classified according to risk groups for Groupe Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) accelerated partial breast irradiation (APBI) and molecular classification and time interval between first and second breast surgery (TI S1S2). Finally, we combined GEC-ESTRO APBI, molecular, and TI S1S2 risk groups, leading to the definition of a new score (named TAM: score based on the combination of time interval [T] between first and second surgery and APBI [A] and molecular [M] classifications) specifically designed for 2nd IBTE oncological outcome analysis. From July 1994 to January 2021, a total of 508 patients received a 2nd CT. At the time of 2nd IBTE, median age was 64.6 years (range, 56.2-72.6). With a median follow-up of 60.9 months (56.2-72.6), the 5-year second local relapse CI rate was 4% (95% confidence interval [95% CI], 2%-6%). The 5-year distant metastasis disease CI rate was 7% (95% CI, 4%-10%). Five-year disease-free and overall survival rates were 89% (95% CI, 86%-93%) and 91% (95% CI, 88%-94%), respectively. In multivariate analysis, TAM score was an independent prognostic factor for all the oncological items (P <.001) except disease-specific survival (P =.07) and overall survival (P =.09). The grade ≥3 late toxicity rate was 12.1%. This analysis of 2nd CT combining lumpectomy with APBrI for 2nd IBTE confirmed the excellent oncological results obtained after 2nd CT. Furthermore, the GEC-ESTRO TAM score appears to be an important prognostic factor, assisting patients and physicians in the decision-making process. [ABSTRACT FROM AUTHOR]

Background: Radiation pneumonitis (RP) is one of the common side effects after adjuvant radiotherapy in breast cancer. Irradiation dose to normal lung was related to RP. We aimed to propose an organ features based on deep learning (DL) model and to evaluate the correlation between normal lung dose and organ features. Methods: Patients with pathology-confirmed invasive breast cancer treated with adjuvant radiotherapy following breast-conserving surgery in four centers were included. From 2019 to 2020, a total of 230 patients from four nationwide centers in China were screened, of whom 208 were enrolled for DL modeling, and 22 patients from another three centers formed the external testing cohort. The subset of the internal testing cohort (n = 42) formed the internal correlation testing cohort for correlation analysis. The outline of the ipsilateral breast was marked with a lead wire before the scanning. Then, a DL model based on the High-Resolution Net was developed to detect the lead wire marker in each slice of the CT images automatically, and an in-house model was applied to segment the ipsilateral lung region. The mean and standard deviation of the distance error, the average precision, and average recall were used to measure the performance of the lead wire marker detection model. Based on these DL model results, we proposed an organ feature, and the Pearson correlation coefficient was calculated between the proposed organ feature and ipsilateral lung volume receiving 20 Gray (Gy) or more (V20). Results: For the lead wire marker detection model, the mean and standard deviation of the distance error, AP (5 mm) and AR (5 mm) reached 3.415 ± 4.529, 0.860, 0.883, and 4.189 ± 8.390, 0.848, 0.830 in the internal testing cohort and external testing cohort, respectively. The proposed organ feature calculated from the detected marker correlated with ipsilateral lung V20 (Pearson correlation coefficient, 0.542 with p < 0.001 in the internal correlation testing cohort and 0.554 with p = 0.008 in the external testing cohort). Conclusions: The proposed artificial Intelligence-based CT organ feature was correlated with normal lung dose in adjuvant radiotherapy following breast-conserving surgery in patients with invasive breast cancer. Trial registration: NCT05609058 (08/11/2022). [ABSTRACT FROM AUTHOR]

Purpose/objective: Adjuvant whole breast radiotherapy and systemic therapy are part of the current evidence-based treatment protocols for early breast cancer, after breast-conserving surgery. Numerous randomized trials have investigated the therapeutic effects of partial breast irradiation (PBI) compared to whole breast irradiation (WBI), limiting the treated breast tissue. These trials were designed to achieve equal control of the disease with possible reduction in adverse events, improvements in cosmesis and quality of life (QoL). In this meta-analysis, we aimed to investigate the differences between PBI and WBI in side effects and QoL. Material/methods: We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect-sizes for available acute and late adverse events. Additionally, we evaluated cosmetic outcomes as well as general and breast-specific QoL using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Results: Sixteen studies were identified (n = 19,085 patients). PBI was associated with a lower prevalence in any grade 1 + acute toxicity and grade 2 + skin toxicity (OR = 0.12; 95% CI 0.09–0.18; p < 0.001); (OR = 0.16; 95% CI 0.07–0.41; p < 0.001). There was neither a significant difference in late adverse events between the two treatments, nor in any unfavorable cosmetic outcomes, rated by either medical professionals or patients. PBI-technique using EBRT with twice-daily fractionation schedules resulted in worse cosmesis rated by patients (n = 3215; OR = 2.08; 95% CI 1.22–3.54; p = 0.007) compared to WBI. Maximum once-daily EBRT schedules (n = 2071; OR = 0.60; 95% CI 0.45–0.79; p < 0.001) and IORT (p = 0.042) resulted in better cosmetic results grade by medical professionals. Functional- and symptom-based QoL in the C30-scale was not different between PBI and WBI. Breast-specific QoL was superior after PBI in the subdomains of "systemic therapy side effects" as well as "breast-" and "arm symptoms". Conclusion: The analysis of multiple randomized trials demonstrate a superiority of PBI in acute toxicity as well breast-specific quality of life, when compared with WBI. Overall, late toxicities and cosmetic results were similar. PBI-technique with a fractionation of twice-daily schedules resulted in worse cosmesis rated by patients. [ABSTRACT FROM AUTHOR]

Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. STROBE-compliant protocol ascertained CWPF outcomes between March 2011–March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. Across 15 centres, 507 patients with median age (54 years, IQR; 48–62), body mass index (25.4 kg/m2, IQR; 22.5–29), tumour size (26 mm, IQR; 18–35), and specimen weight (62 g, IQR; 40–92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11–39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes. This is the analysis of the largest aggregated cohort of patients (n=507, 2011-2021, 15 UK centres) undergoing partial breast reconstruction with a pedicled chest wall perforator flap to avoid deformity following breast conservation. Data demonstrates its applicability in T1-T2 tumours (median size,26 mm, IQR;18-35) with re-excision rates of 15.9 (7.5% during the planned second stage) and 1.8% completion mastectomy. Postoperative complication rates were 4.3% haematoma, 4.3% wound infection, 2.8% delayed wound healing, and 0.2% total flap loss. This study demonstrates that CWPF is a valuable option for patients with a higher tumour-to-breast volume ratio who wish to pursue breast-conserving surgery. [Display omitted] • PartBreCon study : A retrospective cohort study of partial breast reconstruction. • 15 centres, n = 507; T2 (26 mm), Breast conservation in 73.4% A-C cups, BMI (25.4). • Chest Wall Perforator Flaps - LiCAP (54%), AiCAP (19%), LiCAP-LTAP (20%), TDAP (2%). • Shows acceptable complications (12%) - re-operations (2.6%), flap loss (0.6%). • Low Mastectomy (2%) & Low Symmetrisation (1%); FU (23 m), local recurrence (1%). [ABSTRACT FROM AUTHOR]

The study explored the relationship between breast density, compressed breast thickness (CBT) in mammography (MMG) before surgery, and setup errors of the tumor bed after breast-conserving surgery (BCS). The objective was to determine which patients are likely to experience large setup errors under partial breast irradiation (PBI) for early-stage breast cancer. This study included 66 patients who underwent whole breast irradiation (42.56 Gy/16 Fr) using a general Linac with a six-axial moving couch from April to December 2023. Additionally, these cases had MMG taken preoperatively. Two qualified radiographers classified MMG as dense (extremely dense and heterogeneously dense) and non-dense (scattered and fatty). CBT cases of ≥43.5 mm and <43.5 mm were classified as high (H) and low (L), respectively. The position of each clip placed at the surgical cavity wall (2–6 for each patient, 255 clips for all patients) was determined relative to the rib using cone beam computed tomography (a total of 262 data sets of 1, 2, 9, and 16 Fr), and the vector lengths were calculated. The root mean square (RMS) of all clips in each Fr (RMSfr) was calculated, and the course of the variation between each Fr was assessed. Furthermore, the RMS of RMSfr (RMSall) was calculated for all cases. Cases were categorized as dense or non-dense and CBT-H or CBT-L; multiple comparison tests for the median RMSfr and RMSall were conducted using Bonferroni's correction. The median RMSalls of the dense_CBT-L, dense_CBT-H, non-dense_CBT-L, and non-dense_CBT-H groups were 3.6, 4.0, 3.3, and 5.0 mm, respectively. The median RMSall difference between the CBT-H and CBT-L groups was 0.6 mm, whereas non-dense_CBH_H, including the distinction of breast density, increased to >1.0 mm compared with the other groups. Multiple comparison tests revealed a significant difference in the median RMSalls among the four groups (p -value = 0.0065). The table shows the number of cases and the statistics of the four RMSfr for groups in each fraction. The p -values of the combination of CBT and breast density for 1, 2, 9, and 16 Fr were 0.98, 0.71, 0.15, and 0.06, respectively. The median RMSfr in the non-dense_CBT-H group was larger than that in the other groups, which increased from 3.0 to 5.4 mm with increasing fractions. Additionally, the median RMSfr in 16 Fr was the highest at 5.4 mm, which is 1.6 mm higher than the other groups. Errors in the tumor bed setup for PBI after BCS are more pronounced in large and non-dense breasts on MMG. [ABSTRACT FROM AUTHOR]

Accelerated Partial Breast Irradiation (APBI) with external beam IMRT has emerged as an excellent treatment strategy for select early-stage breast cancer patients. Our institutional preference for APBI consists of 3000cGy in 5 non-consecutive fractions with IMRT per the Florence protocol. At our institution, this has recently evolved to include deep-inspiration breath-hold (DIBH) for motion management, along with the preferred use of radiopaque filament marker (FM) for target delineation and daily CBCT-based image guidance. The CTV to PTV margin has been reduced from 10-mm to 5-mm for such patients, in light of reduction in uncertainty of target localization and uncertainty of motion. We hypothesize a reduction in CTV-to-PTV margins from 10 mm to 5 mm with implementation of DIBH and filament marker for IMRT-based APBI will result in non-inferior local control compared to recently published contemporary data. This study was conducted through a retrospective chart review of 16 stage 0 and 57 stage 1 breast cancer patients including 60 "acceptable" and 13 "cautionary" patients per ASTRO APBI consensus guidelines treated at our institution from March 2021 through June 2023 with 5-fraction IMRT APBI, using DIBH for motion management and lumpectomy cavity delineation using a FM. Standard 10-mm margin was used to expand from lumpectomy cavity to CTV for all patients. A reduced 5-mm expansion from CTV to PTV was utilized (compared to 10-mm CTV to PTV expansion in Florence protocol) in light of motion management and target localization techniques described above. Cropping of PTV from skin surface and/or chest wall followed Florence guidelines. With a median follow up of 23.1 months, local control was 100% for patients treated with reduced 5-mm CTV to PTV margins. There were no cases of subacute radiation pneumonitis. Compared to the results of "standard" 10-mm CTV to PTV expansion, the use of 5-mm CTV to PTV margin reduced the mean PTV for these patients by approximately 112 cc (> 80% absolute volume reduction). For patients treated with 5-fraction external beam APBI, the use of DIBH for motion management and filament marker for target localization appears to allow for safe reduction in CTV-to-PTV expansion without reduction in local control. Absolute reduction in PTV with this approach is substantial, with potential implications for cosmetic outcome or other late effects. Longer term follow up will be needed to confirm the durability of these local control and toxicity results and may offer potential for improved cosmesis results. [ABSTRACT FROM AUTHOR]

To evaluate the risk factors associated with the long-term adverse cosmesis, cosmetic deterioration and breast induration in the patients after breast-conserving surgery (BCS) and whole breast irradiation (WBI). This post hoc analysis was performed using data of 614 patients from a phase III, randomized controlled trial comparing hypofractionated radiotherapy (HFRT, WBI at 43.5 Gy in 15 fractions followed by a tumor-bed boost at 8.7 Gy in 3 fractions over 3.5 weeks) with conventional fractionated radiotherapy (CFRT, 50 Gy in 25 fractions followed by 10 Gy in 5 fractions over 6 weeks) after BCS. The patients who had cosmesis results at both baseline and the most recent follow-up were eligible. The endpoints included adverse cosmesis, deterioration of cosmesis and induration. The adverse cosmesis was defined as fair or poor cosmesis based on Harvard 4-scale system. The breast size (CTV volume), boost size and dosimetric parameters of heterogeneity (PTV V 105% , V 107% , V 110% and D 2cc) were collected, and their relative and absolute subjects were both recorded. Logistic regression models were used to assess the relationship between risk factors and these outcomes. The optimal cut-off values of dosimetric parameters were determined using receiver operating characteristic curve (ROC) analyses combined with the optimum Youden index. The clinicopathologic characteristics and dosimetric parameters were comparable between HFRT (n = 311) and CFRT (n = 303) groups. All patients received a tumor-bed boost after WBI; 21 (3.4%) received supra/infraclavicular nodal irradiation, and one of them received axillary nodal irradiation. With the median follow-up of 110.1 months (IQR: 97.5-127.1 months), 68 (11.7%) patients developed adverse cosmesis, 65 (10.6%) had cosmetic deterioration and 50 (8.1%) had breast induration. The incidence of breast adverse effects was similar in HFRT and CFRT groups. The variables including BMI, diabetes, hormonal therapy, adjuvant chemotherapy, surgery to radiotherapy interval, adverse baseline cosmesis, CTV volume, relative PTV V 105% , absolute PTV V 107% , relative boost size, and absolute boost size were included in the multivariable analysis. The results showed that the factors associated with adverse cosmesis were adverse baseline cosmesis and relative boost size ≥ 17.2%; the factors associated with cosmetic deterioration was larger relative boost size; and the factors associated with induration was larger absolute boost size. However, the CTV volume, PTV V 105% , PTV V 107% were not independently associated with the adverse effects. For the patients receiving WBI and tumor-bed boost, the relative or absolute boost size was associated with adverse cosmesis, cosmetic deterioration and breast induration. However, the breast size and dosimetric parameters of dose heterogeneity were not identified to be independently associated with the adverse effects in this study. [ABSTRACT FROM AUTHOR]

Adjuvant radiotherapy after breast-conserving surgery has become an integral part of the treatment of breast cancer. In recent years, the development of radiotherapy technology has made great progress in this field, including the comparison of the curative effects of various radiotherapy techniques and the performance of the segmentation times. The choice of radiotherapy technology needs to be co-determined by clinical evidence practice and evaluated for each individual patient to achieve precision radiotherapy. This article discusses the treatment effects of different radiotherapy, techniques, the risk of second cancers and short-range radiation therapy techniques after breast-conserving surgery such as hypo fractionated whole breast irradiation and accelerated partial breast irradiation. The choice of radiotherapy regimen needs to be based on the individual condition of the patient, and the general principle is to focus on the target area and reduce the irradiation of the normal tissues and organs. Short-range radiotherapy and hypofractionated are superior to conventional radiotherapy and are expected to become the mainstream treatment after breast-conserving surgery. [ABSTRACT FROM AUTHOR]

Introduction: Partial breast irradiation (PBI) has increased in utilization, with the postoperative lumpectomy cavity and clips used to guide target volumes. The ideal timing to perform computed tomography (CT)-based treatment planning for this technique is unclear. Prior studies have examined change in volume over time from surgery but not the effect of patient characteristics on lumpectomy cavity volume. We sought to investigate patient and clinical factors that may contribute to larger postsurgical lumpectomy cavities and therefore predict for larger PBI volumes. Methods: A total of 351 consecutive women with invasive or in situ breast cancer underwent planning CT after breast-conserving surgery at a single institution during 2019 and 2020. Lumpectomy cavities were contoured, and volume was retrospectively computed using the treatment planning system. Univariate and multivariate analyses were performed to evaluate the associations between lumpectomy cavity volume and patient and clinical factors. Results: Median age was 61.0 years (range, 30-91), 23.9% of patients were Black people, 52.1% had hypertension, the median body mass index (BMI) was 30.4 kg/m², 11.4% received neoadjuvant chemotherapy, 32.5% were treated prone, mean interval from surgery to CT simulation was 54.1 days ± 45.9, and mean lumpectomy cavity volume was 42.2 cm3 ± 52.0. Longer interval from surgery was significantly associated with smaller lumpectomy cavity volume on univariate analysis, p = 0.048. Race, hypertension, BMI, the receipt of neoadjuvant chemotherapy, and prone position remained significant on multivariate analysis (p < 0.05 for all). Prone position vs. supine, higher BMI, the receipt of neoadjuvant chemotherapy, the presence of hypertension, and race (Black people vs. White people) were associated with larger mean lumpectomy cavity volume. Discussion: These data may be used to select patients for which longer time to simulation may result in smaller lumpectomy cavity volumes and therefore smaller PBI target volumes. Racial disparity in cavity size is not explained by known confounders and may reflect unmeasured systemic determinants of health. Larger datasets and prospective evaluation would be ideal to confirm these hypotheses. [ABSTRACT FROM AUTHOR]

Background: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. Methods: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. Discussion: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. Trial registration: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Intra‑operative radiotherapy (IORT) is a new alternative way to give radiation therapy. During surgery to remove breast cancer, radiation is given as a single dose directly to the area where the tumor used to be. The aim of the study was to compare the results of IORT as partial breast irradiation and external whole breast irradiation (EBRT) for early breast cancer in elderly patients after breast‑conserving surgery. The results were retrospectively analyzed from a single institution. We report 7‑year results for local control. Settings and Design: Cross‑sectional study. Methods and Material: Between November 2012 and December 2019, 21 Gy partial breast irradiation was applied intra‑operatively to 40 selected patients. Two of these patients were excluded from the study, and 38 patients were evaluated. Also, 38 patients who had EBRT and had similar properties to that of IORT patients were selected to compare the treatment results in terms of local control. Statistical Analysis Used: SPSS version 21 was used for statistical analysis. Patient groups undergoing IORT and EBRT were analyzed with the Kolmogorov–Smirnov test. The groups were examined in terms of demographic features using t‑test, and P < 0.05 was considered as statistically significant. Local recurrence rates were calculated by Kaplan–Meier analysis. Results: The median follow‑up time was 58 months (range 20–95 months). The local control was 100% in both groups, and no local recurrences were observed. Conclusion: IORT seems to be a safe and effective alternative to EBRT for early breast cancer in elderly patients. [ABSTRACT FROM AUTHOR]

Several randomised, phase 3 trials have investigated the value of different techniques of accelerated partial breast irradiation (APBI) for patients with early breast cancer after breast-conserving surgery compared with whole-breast irradiation. In a phase 3 randomised trial, we evaluated whether APBI using multicatheter brachytherapy is non-inferior compared with whole-breast irradiation. Here, we present the 10-year follow-up results. We did a randomised, phase 3, non-inferiority trial at 16 hospitals and medical centres in Austria, Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland. Patients aged 40 years or older with early invasive breast cancer or ductal carcinoma in situ treated with breast-conserving surgery were centrally randomly assigned (1:1) to receive either whole-breast irradiation or APBI using multicatheter brachytherapy. Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with a supplemental boost of 10 Gy to the tumour bed, and APBI was delivered as 30·1 Gy (seven fractions) and 32·0 Gy (eight fractions) of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was ipsilateral local recurrence, analysed in the as-treated population; the non-inferiority margin for the recurrence rate difference (defined for 5-year results) was 3 percentage points. The trial is registered with ClinicalTrials.gov , NCT00402519 ; the trial is complete. Between April 20, 2004, and July 30, 2009, 1328 female patients were randomly assigned to whole breast irradiation (n=673) or APBI (n=655), of whom 551 in the whole-breast irradiation group and 633 in the APBI group were eligible for analysis. At a median follow-up of 10·36 years (IQR 9·12–11·28), the 10-year local recurrence rates were 1·58% (95% CI 0·37 to 2·8) in the whole-breast irradiation group and 3·51% (1·99 to 5·03) in the APBI group. The difference in 10-year rates between the groups was 1·93% (95% CI –0·018 to 3·87; p=0·074). Adverse events were mostly grade 1 and 2, in 234 (60%) of 393 participants in the whole-breast irradiation group and 314 (67%) of 470 participants in the APBI group, at 7·5-year or 10-year follow-up, or both. Patients in the APBI group had a significantly lower incidence of treatment-related grade 3 late side-effects than those in the whole-breast irradiation group (17 [4%] of 393 for whole-breast irradiation vs seven [1%] of 470 for APBI; p=0·021; at 7·5-year or 10-year follow-up, or both). At 10 years, the most common type of grade 3 adverse event in both treatment groups was fibrosis (six [2%] of 313 patients for whole-breast irradiation and three [1%] of 375 patients for APBI, p=0·56). No grade 4 adverse events or treatment-related deaths have been observed. Postoperative APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is a valuable alternative to whole-breast irradiation in terms of treatment efficacy and is associated with fewer late side-effects. German Cancer Aid, Germany. [ABSTRACT FROM AUTHOR]

To report the 10-year late side-effects and cosmetic results of the GEC-ESTRO multicentric phase 3 accelerated partial breast irradiation (APBI) trial. Women aged 40 years or older with stage 0-IIA breast cancer who underwent breast-conserving surgery (BCS) with clear resection margins were randomly assigned to receive either whole-breast irradiation (WBI) of 50 Gy with a tumor-bed boost of 10 Gy or APBI with interstitial brachytherapy. The non-inferiority of APBI in terms of local tumor control as primary end-point has been confirmed. Here, we report the secondary endpoints of late side-effects and cosmesis at 7.5 and 10 years of follow-up. This trial is registered with ClinicalTrials.gov number NCT00402519. Between 2004, and 2009, we randomly assigned 1328 women to receive either WBI (n=673) or APBI with interstitial brachytherapy (n=655); 1184 patients comprised the as-treated population and among these 10-year data on late side-effects and cosmetic results were available in 688 patients (313 in the WBI group and 375 in the APBI group). At 7.5 and 10 years 10 (2.7%) and 4 (1.3%) patients in the WBI group and 2 (0.4%) and 1 (0.3%) patients in the APBI group had grade 3 skin teleangiectasia (p=0.02 at 7.5 years and p=0.18 at 10 years). At 7.5 and 10 years 2 (0.5%) and 5 patients (1.6%) in the WBI group and 2 (0.4%) and 3 (0.8%) in the APBI group developed grade 3 late subcutaneous tissue toxicity (p=0.62 at 7.5 years and p=0.53 at 10 years). The incidence of grade 2-3 breast pain at 7.5 and 10 years was 1.6% and 1.0% after WBI versus 1.1% and 0.8% after APBI (p=0.39 at 7.5 years and p=0.93 at 10 years). At 7.5 years brachial lymphoedema occurred more frequently after WBI compared to APBI (5.4% vs 2.2%; p=0.03). At 7.5 and 10 years' follow-up, according to the patients' view, 31.9% and 33.8% of patients had excellent cosmetic results in the WBI group versus 44.3% and 45.0% of patients in the APBI group (p=0.001 at 7.5 years and p=0.002 at 10 years); when judged by the physicians, 31.7% and 33.2% of patients in the WBI group versus 40.0% and 40.0% of patients in the APBI group, had excellent cosmetic results, respectively (p=0.05 at 7.5 years and p=0.2 at 10 years). Long-term toxicity profiles and cosmetic results were similar in patients treated with BCS followed by either APBI with interstitial brachytherapy or conventional WBI, with significantly fewer skin teleangiectasia and brachial lymphoedema accompanied with a slightly better cosmetic results after APBI with interstitial brachytherapy. These findings provide further clinical evidence for the routine use of sole interstitial multicatheter brachytherapy after BCS. [ABSTRACT FROM AUTHOR]

Our prospective mono-institutional non-randomized open-label study (NTC05142202) evaluates the impact of adjuvant accelerated partial breast irradiation with HDR brachytherapy on health-related quality of life (QOL) of patients with low-risk early-stage breast cancer after breast-conserving surgery. It is to report an interim analysis of a novel fractionation scheme's influence on patients' QOL. 147 patients were enrolled in a prospective study during recruitment between October 2021 and December 2023. Treatment was performed using postoperative interstitial HDR brachytherapy and was given for three days in 5 fractions of 5,4 Gy up to a total dose of 27,0 Gy. Health-related QOL was assessed using the QLQ-C30 questionnaire and breast cancer-specific HRQL module (EORTC QLQ-BR23) before APBI, one month, three months, six months after treatment, and every six months after that. Both questionnaires contain functional scales (a higher score represents better functioning) and symptom scales (a higher score represents a higher level of symptoms). This analysis presents a preliminary report of the short-term (6 months) QOL of 111 patients who completed six months of follow-up (FU). Repeated measures ANOVA was used to compare HRQL scores between time points. A p-value below 0.05 was considered statistically significant. There was a statistically significant increase in the mean of social functioning scale (SF, Fig. 1A; p=0.019) and an increase in the constipation symptoms scale (CO, Fig. 1B; p=0.004) assessed in EORTC QLQ-C30 scale. The analysis of EORTC QLQ-BR23 module scales showed an increase in body image functional scale (BRBI, Fig. 1C, p=0.004) and future perspective functional scale (BRFU, Fig.1D; p<0.001). In symptoms scales, there was an increase in the systemic therapy side effects scale (BRST, Fig. 1E; p=0.001) and a decrease in breast symptoms (BRBS, Fig. 1F; p=0.006). There were no other statistically significant changes in the functional or symptom scales of the QLQ-C30 and BR23 questionnaires. There is no deterioration of short-time health-related quality of life of patients treated with 5 × 5,4 Gy HDR APBI. We observed increased symptoms only in scales linked with adjuvant systemic therapy. After six months of FU, an increase in body image functional scale and a decrease in breast symptoms after the treatment are worth noticing the most promising observations. [ABSTRACT FROM AUTHOR]

A prospective mono-institutional non-randomized open-label study (NTC05142202) is being carried out to establish the role of adjuvant multicatheter interstitial high-dose-rate brachytherapy (HDR-BT) in doubly accelerated and radiobiologically equivalent irradiation scheme of 5 × 5,4 Gy delivered in 3 days of treatment (High Five, HiFi-APBI) compared to the adopted long-term standard of APBI realized in 4-5 days (7-8 × 4-4,3 Gy) in selected women with low-risk invasive breast cancer or carcinoma in-situ. It is to report an interim analysis on the first 1- and 3-month early toxicity profiles and 1- and 3-month early cosmetic outcome results of a novel fractionation scheme adjuvant to breast-conserving surgery. Early low-risk breast cancer patients (pT is-2 N 0) were recruited between October 2021 and December 2023 (recruitment closed on 12/31/2024 according to protocol). Postoperative adjuvant treatment with interstitial HDR-BT was given for three days (5 fractions of 5,4 Gy; 6 hours apart; total dose 27,0 Gy) on an outpatient basis. Follow-up (FU) is continued one-month post-treatment, then three months up to 2 years, and six months up to 5 years. Early toxicity incidence (radiodermatitis, hematoma, breast infection, intraoperative breast damage, breast pain) is being assessed according to Common Terminology Criteria for Adverse Events v5.0 (CTCAE) up to 3 months FU. We also assess early 1- and 3-month Harvard scale-based cosmetic outcomes and record patients' feedback on a four-grade subjective breast appearance scale (excellent, good, satisfying, poor). Photographic documentation is being secured. One hundred forty-seven women aged 65 (51-85) were enrolled. At the time of analysis, all patients reached 1-month FU, and 132 (89,9%) reached 3-month FU. Early toxicities at one-month FU were: radiodermatitis G1 - 4 (2.7%); hematoma G1 - 21 (14.3%); breast pain G1 - 24 (16.3%), G2 - 2 (1.4%). Early toxicities at three-month FU were: radiodermatitis G1 - 2 (1.5%); hematoma G1 - 4 (3%); breast pain G1 - 18 (13.6%), G2 - 1 (0.8%). No breast infections occurred. Patients subjectively assessed their cosmetic outcome after one-month post-treatment as excellent at 57.8%, good at 36.1%, satisfying at 5.4%, and poor at 0.7%; after three months, excellent at 61.4%, good at 31.1%, satisfying at 7.1%, and poor at 0.0%. Clinicians assessed cosmesis on the Harvard scale after one month as grade I - 9.5%, II - 81.6%, III - 8.9%, IV - none; after three months as grade I - 21.2%, II - 74.2%, III - 4.6%, IV - none. The incidence of early 1- and 3-month toxicity events is low and improves quickly. Hematomas heal quickly and spontaneously. Rare local and slight painful sensations are more persistent but do not disturb patients' daily activity. Patients assess their cosmesis much better subjectively than clinicians do according to the Harvard scale. Cosmesis seems to improve over time. In an interim analysis, the HiFi-APBI regimen appears to be very well tolerated regarding early toxicity. [ABSTRACT FROM AUTHOR]

As an alternative to the standard 4 to 6 weeks of breast-conserving surgery with whole breast irradiation, a two-day short course accelerated partial breast irradiation (APBI) is available proposed in Triumph-T trial. We present the 2-year follow-up results from a single institution of a 3-fraction APBI delivered using the Strut-Adjusted Volume Implant (SAVI) brachytherapy. Retrospective analysis was conducted to evaluate the efficacy of an ultra-hypofractionated 2-day APBI schedule [22.5 Gy in 3 fractions, Bi-daily, ∼6 hours apart]. Women aged 40 years or older with early-stage breast cancer with diagnosis pTis or pT1-2 underwent breast-conserving surgery and received APBI using high-dose-rate Ir-192 SAVI-brachytherapy. The SAVI applicator is offered in four sizes, each designed to accommodate different cavity volumes: 6-1 mini, 6-1, 8-1, and 10-1. During follow-up (2019-2021), data was gathered on patient and tumor characteristics, treatment summary, oncologic outcomes, and both acute and late treatment-related toxicities, using the Common Terminology Criteria for Adverse Events (CTCAE) v5. Adverse events occurring within 90 days following the completion of APBI were defined as acute, whereas those thereafter were considered late. A total of 103 female patients (median age, 67 years [range (R), 40-92 years] mainly with pT1 tumors (77.7%) underwent APBI using SAVI-brachytherapy. Seventy-seven percent of the patient had invasive carcinoma histology and 22.3% were Ductal carcinoma in situ (DCIS). Median tumor size was 10 mm [R, 1.0-30.0 mm]. There were 91.3% estrogen positive and 84.5% progesterone receptors positive tumors, while Her2neu was positive in 1.9% of cases. Post-APBI, 88.3% of patients received adjuvant hormonal therapy and 7.8% received adjuvant chemotherapy. With a median follow-up of 36.4 months [R, 2.3-53.0 months], the most commonly reported toxicities were hyperpigmentation (47.6%) followed by skin induration (32.0%). Acute grade 1 toxicities were seen in 35.0% of cases, including 27.2% hyperpigmentation, 7.8% skin induration, 6.8% breast pain, 2.9% fatigue, 1.9% moist desquamation, and 1.0% erythema. Late grade 1 toxicities were seen in 53.4% of cases, including 28.2% skin induration, 24.3% hyperpigmentation, 17.5% breast pain, 4.9% fatigue, 1.9% telangiectasia, and 1.0% moist desquamation. No acute or late grade 2+ toxicities were observed. Fifteen patients developed late grade 1 fat necrosis within a median 17.3 months [R, 4.2-38.2 months], 12 were asymptomatic and 3 were symptomatic. Six patients developed breast tissue fibrosis. There were 2 (1.9%) local recurrences. Two-year overall survival following APBI was 98.1%. Retrospective analysis of 2-year follow-up of 103 patients treated at our center using 3-fraction APBI with SAVI- brachytherapy, after breast-conserving surgery demonstrates feasibility and shows excellent oncologic and cosmetic outcomes. APBI presents a viable alternative to WBI in terms of treatment efficacy and is well tolerated by patients. [ABSTRACT FROM AUTHOR]

The study aims to present the long-term results of 508 cases of early breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial multicatheter high-dose-rate brachytherapy (HDR-BT) following breast-conserving surgery (BCS) in a single institution. Between July 2006 and December 2020, a total of 514 cases of low-risk invasive and in situ carcinoma after BCS were treated with APBI using interstitial multicatheter HDR brachytherapy (MIB) at our department and 508 who met the inclusion criteria were analyzed. The inclusion criteria were: ZUBROD 0 or 1, age ≥50 years, pT1-2aN0 cM0, tumor size ≤3 cm, unifocal, invasive carcinoma without neuroinvasion or angioinvasion, with a minimal surgical margin of 2 mm or DCIS with a minimal margin of 5 mm, without extensive intraductal components, positive estrogen receptors. A total dose of 32 Gy in 8 fractions was delivered twice daily with a minimum 6-hour interval. The recommended dose constraints from the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC ESTRO) were followed. The primary endpoint was local recurrence. The median age was 65 years (range 46-86 years). The median follow-up was 101 months (range 5-209 months). No serious complications occurred during the procedure and all patients completed the treatment without interruptions. The treatment was well tolerated. In the first 40 cases the 2D treatment planning was used, while in the subsequent cases - 3D treatment planning. The recommended dose-volume limits for the implant, planning target volume (PTV) and organs at risk (OARs) were met. The mean volume of the PTV was 74 cc, with the average coverage with the prescribed dose (PTV ref) of 94%. The mean conformity index (COIN) was 0.69, while the mean dose homogeneity index (DHI) was 0.67. There were no grade ≥ 3 complications. In the whole group, a total of 10 local recurrences (1.96%) were observed. In 3 cases distant metastases (0.6%) and ipsilateral breast tumor recurrence in 8 cases (1.57%) were observed. The 5- and 10-year overall survival (OS) was 97.5% and 96.6%, respectively. The 5- and 10-year disease-free survival (DFS) was 95.6% and 91.3%, respectively. APBI with interstitial multicatheterhigh-dose-rate brachytherapy is a safe and effective treatment, associated with a good toxicity profile and low relapse rates. We believe that patient selection criteria should be revised and possibly expanded. However, further studies are required to validate this approach. [ABSTRACT FROM AUTHOR]

• Single-fraction partial breast irradiation, followed by surgery after 3 months, leads to a high rate of pathologic response. • A single dose of 20 Gy to the breast tumor is acutely well tolerated. • The 3-month preoperative interval is suboptimal for late toxicities and cosmesis. A novel approach using single-fraction preoperative partial breast irradiation (PBI) for low-risk breast cancer is under study. We sought to investigate the rate of pathologic response (pR), toxicities and cosmetic results related to this new treatment strategy. Women of 65 years or older with stage I unifocal luminal A breast cancer were eligible for inclusion in this phase I prospective trial. Patients received a single 20 Gy dose of PBI followed by breast-conserving surgery (BCS) 3 months later. The primary endpoint was the pR rate, and the secondary endpoints were radiation therapy-related toxicity and cosmetic results. Thirteen patients were treated, with a median age of 71. Eleven patients (84.6 %) had pR with a median residual cellularity of 1 % (range: 0–10 %). At median follow-up of 48.5 months, no recurrences or cancer-related deaths were recorded. Acute radiation therapy-related toxicity were limited to grade 1 dermatitis and breast pain. At the 1-year follow-up, there were one grade 2 fat necrosis and two grade 3 toxicities (wound infection and hematoma). Only grade 1 toxicities remained at 2 years, but one grade 2 toxicity (fibrosis/induration) developed by the 3-year follow-up. Three-year patient-reported cosmetic outcomes were good or excellent in 60 % of patients. Single-fraction preoperative PBI preceding BCS for low-risk breast cancer is feasible, relatively well tolerated and leads to a high level of pR. The 3-month interval after PBI seems to place surgery in a post-radiation inflammatory phase. Further delay between PBI and surgery could improve pR and cosmetic outcome. NCT03917498. [ABSTRACT FROM AUTHOR]

• Preoperative single-fraction partial breast irradiation is safe and feasible for elderly patients with low-risk breast cancer • The risk of recurrence is low in single fraction pre-operative breast radiation therapy • Preoperative single-fraction partial breast irradiation is associated with very low rates of surgical complications and of acute and late radiation toxicity • Preoperative single-fraction partial breast irradiation is associated with high rates of excellent cosmetic outcome Preoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI. In this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1–2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence. Twenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences. Preoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population. [ABSTRACT FROM AUTHOR]

Accelerated partial breast irradiation (APBI) has been shown to be equivalent to whole breast irradiation in multiple randomized clinical trials though fractionation, technique, and patient position varies widely between trials. Building on our institutional experience of prone APBI delivered in 5 fractions, we designed a randomized trial hypothesizing that 3-fraction APBI would be non-inferior to 5-fraction APBI with respect to fibrosis. Post-menopausal women who had undergone breast-conserving surgery for invasive disease ≤ 2 cm (any grade) or for screen-detected ductal carcinoma in-situ ≤ 2.5 cm (grade 1-2), negative margins, and clinically or pathologically node negative were enrolled on this randomized, controlled, non-inferiority trial. Patients were randomly assigned (1:1) to receive APBI delivered prone 30 Gy in 5 fractions (5F) daily (control) or 24Gy in 3 fractions (3F) every other day. Standard tangential beams were used to deliver radiation using field-in-field or intensity modulated radiation therapy. The primary endpoint was that the rate of post-treatment radiation fibrosis (grades 2+) on the 3F arm is not more than 10% worse than the expected rate on the 5F arm by 2 years with one sided alpha of 0.025 and power of 80%. Secondary endpoints included local recurrence (LR), regional recurrence (RR) distant metastasis (DM), contralateral breast cancer, and physician and patient rated cosmesis. This trial is registered with ClinicalTrials.gov, NCT02276885. Between October 2014 and May 2021, we obtained consent from 320 patients of whom 308 were randomized (12 screen-failures), 155 to 5 F arm and 153 to 3 F arm. After excluding 2 additional screen failures and 22 patients who withdrew consent, 284 patients were treated, 144 patients in the 5F arm and 140 in the 3F arm. Within 2 years, grade 2+ fibrosis occurred in 18.3% (25/137) of patients in the 5F arm and 12.3% (17/138) in the 3 F arm meeting criteria for non-inferiority (lower edge of 95% CI -0.025). At a median follow up of 54 months (range = 1-108) the rate of RFS including LR, RR or DM was 95% (3 deaths, 1 LR and 2 DM) (95% CI = 88%-98%) in the 5 F arm and 93% (5 LR, 1 RR, 4DM, and 5 deaths including 2 of the DM) (95% CI = 86%-96%) in the 3F arm. Within 2 years, 93.4% (128/137) patients were recorded as having good/excellent physician-rated cosmesis in the 5F arm and 97.8% (135/138) in the 3F arm. Within 2 years, 83.6% (112/134) of patients rated their own cosmesis as good/excellent in the 5 F arm and 78.1% (107/137) in the 3 F arm. APBI delivered prone with 24 Gy in 3 fractions is non-inferior to 30 Gy in 5 fractions with respect to fibrosis. Both groups demonstrate low rates of LR. This trial supports the use of APBI in this low-risk patient population and provides novelty with regard to an alternative fractionation scheme and the use of mini-tangents in the prone position. [ABSTRACT FROM AUTHOR]

Moderate hypofractionation in the management of localized breast cancer is considered standard of care. Data suggests its use in the setting of regional nodal irradiation (RNI) yields equivalent oncologic and cosmetic outcomes but has not yet achieved universal acceptance into practice. The risk of lymphedema (LA) has not been the focus of study in this setting and therefore, we sought to evaluate the risk and establish the rate of moderate or marked LA for patients treated with hypofractionated RNI utilizing an established and commonly used hypofractionation treatment scheme with standardized treatment volumes for patients with node-positive breast cancer. Women with node positive breast cancer who underwent definitive surgical resection were eligible for enrollment. Breast surgery may have been lumpectomy (Lp), mastectomy without reconstruction (M-R), or mastectomy with reconstruction (M+R). Nodal staging by sentinel lymph node (SLN) or by axillary lymph node (ALN) dissection were included. Patients could undergo neoadjuvant or adjuvant chemotherapy at the discretion of the treating medical oncologist. Breast and RNI was administered to 42.56 Gy in 16 daily fractions. The dissected axilla was excluded as a target volume in patients who underwent ALN dissection. Primary endpoint was rate of LA at 3 years following RNI for two cohorts, SLN (cohort A) and ALN (cohort B). Lymphedema was defined as ≥ 10% increase in arm circumference over baseline circumference as compared to the contralateral arm measured every 6 months for the first 3 years. Per protocol-defined to declare moderate hypofractionation non-inferior to recent historical controls cohorts A and B rate of lymphedema were estimated to be 6% and 10% respectively, a non-inferiority margin of +/- 7% was used. Secondary objectives included 5-year oncologic outcomes, grade 3 or higher toxicities, cosmesis and patient reported outcomes. Between September 2015 and July 2021, a total of 134 women were enrolled, 84 underwent SLN only and 50 completed ALN dissection. Mean age was 58.1 years for cohort A and 62.5 years for cohort B. Lp, M+R, and M-R was performed in 58.2%, 19.4, and 30% respectively. LA was observed in 11 patients (13.1%) with SLN only (P = 0.5897) and 9 patients (18%) who underwent ALN dissection (P = 0.65971). Only 2 patients developed grade 2 LA (limiting instrumental activities of daily living) and no grade 3 (limiting self-care activities of daily living) was observed. At 36 month follow up 85.5% in the lumpectomy group and 75.9% in the mastectomy with reconstruction group had excellent or good cosmesis. Moderate hypofractionation did not meet the criteria defined by the protocol for non-inferiority. However, the absolute rates of LA remain low and predominantly grade 1. Cosmetic outcomes in this advanced disease group of patients are favorable. This data does not appear to support the argument that the risk of LA is a reason to avoid moderate hypofractionated regional nodal irradiation. [ABSTRACT FROM AUTHOR]

Purpose: Finding a better treatment position (prone or supine) for wholebreast irradiation for Chinese female patients diagnosed with breast cancer by identify the associations between predictive somatotype parameters and dosimetric gains. Materials and methods: Two volumetric-modulated arc therapy (VMAT) plans were deployed for whole-breast irradiation in supine and prone position with a total dose of 50 Gy in 25 fractions. Dose-volume parameters were compared and analysed both in the target volume and organs at risk, and equivalent uniform dose-based figure-of-merit (fEUD) models were further used to quantitatively evaluate the overall merits of the two plans. Body shape parameters, including body mass index (BMI), body surface area (BSA), breast shape, cup size, bust size and chest size, were collected. Anatomic features such as the central heart distance (CHD) were measured on supine CT. Spearman's correlation analysis, receiver operating characteristic (ROC) curve analysis, and the linear regression models were conducted. Results: Doses to the heart and left anterior descending coronary artery (LADCA) are greater in left-sided breast cancer (BC) patients in the prone position than in the supine position, and the opposite was true for right-sided BC patients (p<0.001). 19 of 63 patients (5 left-sided and 14 right-sided BC) achieved greater benefit from the prone position according to the fEUD score. Right-sided BC patients with a bust size ≥92.25 cm, drop-type breasts and cup size ≥B are very likely to benefit from prone-position radiotherapy. The CHD is significantly positively associated with △fEUD among right-sided BC patients (rho=0.506, p=0.004). Using a cut-off point of 2.215, the CHD had 71.4% sensitivity and 81.2% specificity in predicting a successful prone plan. Conclusions: Right-sided BC patients had better dosimetric gain in the prone position than left-sided BC patients. The CHD is an especially good and novel predictor that could help to select prone-benefitting right-sided BC patients. [ABSTRACT FROM AUTHOR]

We report on the early clinical outcomes of a prospective series of early breast cancer (EBC) patients treated with ultra-hypofractionated post-operative whole-breast irradiation (WBI) after breast-conserving surgery (BCS) and axillary management. Primary endpoints were patient's compliance and acute toxicity. Secondary endpoints included physician-rated cosmesis and ipsilateral breast tumour recurrence (IBTR). Acute toxicity was evaluated at the end of WBI, 3 weeks and 6 months thereafter, according to the Common Terminology Criteria for Adverse Events (v. 5.0). Patients were treated between September 2021 and May 2022. The treatment schedule for WBI consisted of either 26 Gy in 5 fractions over one week (standard approach) or 28.5 Gy in 5 fractions over 5 weeks (reserved to elders). Inverse planned intensity-modulated radiation therapy (IMRT) was used employing a static technique. A total of 70 patients were treated. Fifty-nine were treated with the 26 Gy/5 fr/1 w and 11 with the 28.5 Gy/5 fr/5 ws schedule. Median age was 67 and 70 in the two groups. Most of the patients had left-sided tumours (53.2%) in the 26 Gy/5 fr/1 w or right-sided lesions (63.6%) in the 28.5 Gy/5 fr/5 ws group. Most of the patients had a clinical T1N0 disease and a pathological pT1pN0(sn) after surgery. Ductal invasive carcinoma was the most frequent histology. Luminal A intrinsic subtyping was most frequent. Most of the patients underwent BCS and sentinel lymph node biopsy and adjuvant endocrine therapy. All patients completed the treatment program as planned. Maximum detected acute skin toxicities were grade 2 erythema (6.7%), grade 2 induration (4.4%), and grade 2 skin colour changes. No early IBTR was observed. Ultra-hypofractionated WBI provides favourable compliance and early clinical outcomes in EBC after BCS in a real-world setting. [ABSTRACT FROM AUTHOR]

To analyze long-term results of two multicenter prospective single-arm trials (ARO-2010-01 and ARO-2013-04) investigating adjuvant hypofractionated radiotherapy (HF) with simultaneous integrated boost (SIB) after breast-conserving surgery (BCS). Eligible patients had histopathologically confirmed unifocal breast cancer planned for whole breast irradiation plus boost radiotherapy to the tumor bed. In both studies, a total dose of 40 Gy was applied to the whole breast and of 48 Gy to the tumor bed in 16 fractions of 2.5 and 3.0 Gy. Radiotherapy could be given either as three-dimensional conformal radiotherapy (3D-CRT) or as intensity-modulated radiotherapy (IMRT). The primary study objectives were feasibility and security within an observation period of six months. The current investigation focuses on long-term efficacy and toxicities. Between 2011 and 2014, both trials enrolled 300 patients in total. Data from 274 of these patients could be used for the current analysis. The median follow-up time was 60 months and the 5-year disease-free survival 92.1%. Three patients suffered a local recurrence (after 36–72 months) while a regional recurrence occurred in one patient (after 17 months). The 5-year local control rate in the breast was 99.6%. 63.5% of all patients did not report any late radiation-related toxicity, 28.5% reported grade 1 and 7.3% grade 2 toxicities. The highest late toxicity was grade 3 in 2 women (0.7%, telangiectasia and lymphedema of the breast). Our analysis demonstrates favorable efficacy and low rates of long-term side effects of HF with SIB after BCS. Randomized controlled phase III trials are ongoing. • Hypofractionated breast radiotherapy with SIB was safe and feasible. • The local control rate at 5 years was 99.6%. • The rate of late grade 3 toxicity was 0.7%. [ABSTRACT FROM AUTHOR]

Breast fibrosis (BF) is one of the most reported late toxicities following whole breast radiotherapy (WBRT). This study aims to find out biomarkers that can be used in individual risk assessment of BF. The correlation of surgical and dosimetric parameters with BF was also analyzed. Two hundred twenty-three invasive breast carcinoma patients who underwent breast conserving surgery and adjuvant WBRT +/- regional nodal irradiation were included in the study. Age, lumpectomy size, microscopic tumor size, systemic treatment status, the time from surgery to WBRT were the clinicopathological features evaluated. The volume of the whole breast and boost volume and their ratio, the maximum and mean dose of the breast, the dose of 95% of breast volume, the percent of the breast volume that had 50Gy and more (V50), V55, and V60 were the parameters evaluated. Neutrophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte, systemic immune-inflammation index, hemoglobin, and C-reactive protein (CRP) levels before WBRT, the ratio of hemoglobin and CRP levels before and after WBRT were the biomarkers that investigated for prediction of BF. The median follow-up time was 22.5 (6-85.29) months. Grade 1 fibrosis was observed in 107 (47%), and grade 2 fibrosis in 7 (3.1%) patients. In the grade 1-2 fibrosis group lymphatics irradiation rate was higher (51.8% vs 35.8%, p= 0.016) and the treated breast in this group were mostly left-sided (left side percentages: 38.5% vs 56.1%; p= 0.008). CRP-Ratio was the only parameter that had statistically significant ROC curve (Area under the curve: 0.412, p= 0.024). The CRP-Ratio value of 0.544 was found to have the best sensitivity (35.65%) and specificity (84.25%). [ABSTRACT FROM AUTHOR]

To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ≤3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9–75.4 cc), and the external-V 100 was 43.1 cc (12.87–107 cc), representing 5% of the breast tissue irradiated with a median CTV D 90 of 6.2 Gy (5.6–6.28 Gy). The entire local treatment (BCS& MITBI-4f-AMBI) was completed at a median of 8 days (4–10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11–51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes. [ABSTRACT FROM AUTHOR]

Adjuvant whole breast irradiation (AWBI) improves local control and survival in breast cancer patients after breast-conserving surgery. Between 2010 and 2017, 823 patients ≥ 60 years with ER-positive, Her-2 negative, clinically N0 breast cancer underwent breast-conserving surgery (BCS) at the West Pomeranian Oncology Center. Intraoperative radiotherapy (IORT) with kV photons was applied to 199 (24.2%) patients according to the IORT protocol, and AWBI only was applied to 624 (75.8%). IORT patients in cases with lymph node metastasis, lobular type presence, extensive in situ components, lymphatic vessel invasion, or resection margin < 2 mm, additionally underwent AWBI. Median follow-up was 74 months. There were two (1%) breast relapses in the IORT protocol group and one (0.2%) in the AWBI-only group. In each group, one axillary lymph node relapse was diagnosed (0.5% and 0.2%, respectively). There were two local relapses in the IORT-only group, and they were treated further with BCS and AWBI. Although locoregional relapse-free survival differed between the AWBI-only and IORT protocol groups (98.5% vs. 99.7%, p = 0.048), the local control, distant metastasis-free survival, and breast cancer-specific survival were similar. IORT is a reasonable option to avoid AWBI in ER-positive, Her-2 negative, cN0 women with breast cancer aged ≥ 60 years. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) in patients with breast cancer. Materials and Methods: A total of 27 patients after breast-conserving surgery were included in this study. Patients were planned on a four-dimensional computerized tomogram, and contouring was done using RTOG guidelines. The dose was 34 Gy/10#/2 week to the breast and 40 Gy/10#/2 week to the tumor bed as SIB with volumetric modulated arc technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs-at-risk were calculated. Toxicities and cosmesis were assessed using RTOG/LENT/SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier curves. Results: The mean age of the patients was 42 years. Left and right breast cancers were seen in 17 (63%) and 10 (37%) patients, respectively. The mean values of ipsilateral lung V16 and contralateral lung V5 were 16.01% and 3.74%, respectively. The mean heart doses from the left and right breast were 7.25 Gy and 4.37 Gy, respectively. The mean doses to the contralateral breast, oesophagus, and Dmax to brachial plexus were 2.64 Gy, 3.69 Gy, and 26.95 Gy, respectively. The mean value of thyroid V25 was 19.69%. Grade 1 and 2 acute skin toxicities were observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema, and induration were observed in 1 (3.7%), 2 (7.4%), and 4 (14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient. The median follow-up was 51 months (range, 12 to 61 months). At four years, breast induration, edema, and fibrosis were observed in 1 (3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred in 1 (3.7%) and 2 (7.4%) patients, respectively. DFS and OS at four years were 88% and 92%, respectively. Conclusion: With this radiotherapy schedule, acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS, and OS were good. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer in the female population. Adjuvant radiotherapy has become increasingly important as conservative treatment. Muticatheter interstitial brachytherapy is a type of radiation technique wherein the radioactive sources are directly implanted into or close to the target tissue and may be considered an extremely precise, versatile, and variable radiation technique. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy, with particular focus on the implant description, limits, and advantages of the technique. Breast cancer represents the second leading cause of cancer-related death in the female population, despite continuing advances in treatment options that have significantly accelerated in recent years. Conservative treatments have radically changed the concept of healing, also focusing on the psychological aspect of oncological treatments. In this scenario, radiotherapy plays a key role. Brachytherapy is an extremely versatile radiation technique that can be used in various settings for breast cancer treatment. Although it is invasive, technically complex, and requires a long learning curve, the dosimetric advantages and sparing of organs at risk are unequivocal. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy, with longer follow-up than new, emerging radiation techniques, whose effectiveness is proven by over 20 years of experience. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy to perform breast lumpectomy boost, breast-conserving accelerated partial breast irradiation, and salvage reirradiation for ipsilateral breast recurrence, with particular focus on the implant description, limits, and advantages of the technique. [ABSTRACT FROM AUTHOR]

Introduction: Oncoplastic breast-conserving surgery (OBCS) can cause breast asymmetry. Although contralateral breast surgery to achieve symmetry was offered to these patients, the uptake of symmetrisation was variable. We aimed to determine the factors that deter patients with breast cancer undergoing OBCS from opting for symmetrisation.Methods: All patients with breast cancer who underwent OBCS of displacement type with no symmetrisation were prospectively surveyed to explore the social, economic, psychological and physical reasons against symmetrisation.Results: A total of 28 patients participated in a survey administered at a mean 21.6 (range 2-47) months after OBCS. A combination of factors, such as worry and desire to treat breast cancer first (67.9%), not being overly concerned about breast cosmesis (57.1%) and fear of pain from additional operation (28.6%), deterred patients from immediate symmetrisation. Worry and desire to treat breast cancer first was the most important single factor for 50% of the patients. Reasons for no delayed symmetrisation included not being overly concerned about breast cosmesis (70.4%), fear of breast cancer recurrence (48.1%) and being happy with current breast cosmesis (33.3%), with the former two reasons equally cited as the single most important deterrent by 30% of patients each.Conclusion: A combination of factors may deter patients from symmetrisation. The most significant factors deterring OBCS among patients were worry and desire to treat breast cancer first for immediate symmetrisation, and not being overly concerned about breast cosmesis and fear of breast cancer recurrence for delayed symmetrisation. Reassuring these patients may increase their uptake of symmetrisation, thereby improving patient cosmesis and satisfaction. [ABSTRACT FROM AUTHOR]

We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients (scheme A) received 3.5 Gy/day ×10 fractions (breast/ASA) followed by two 4 Gy fractions with electrons to the affected breast quadrant within 16 days. In total, 77 patients (Scheme B) received 2.7 Gy/day for 16 consecutive fractions (breast/ASA) within 22 days, while concurrently, the affected breast quadrant received an electron booster dose of 0.8 Gy for the first 13 fractions. Amifostine was offered to 252/367 patients. Early radiation toxicity was minimal. Regarding late toxicities, symptomatic breast edema was noted in 2.2%, asymptomatic breast fibrosis in 1.9%, and arm lymphedema in 3.7% of patients. Amifostine reduced early radiation dermatitis (p = 0.001). In total, 2.2% of patients developed contralateral breast and 1.6% other carcinomas. Locoregional recurrence (LR) occurred in 3.1% of patients (0% for in situ carcinomas). Positive margins after surgery, extracapsular node invasion, and HER2-enriched/triple-negative tumors were linked with significantly worse LR-free survival. The involvement of more than three nodes and luminal type other than A were independent prognostic variables of metastasis and death events. HypoAR delivering a biological dose of 50–52 Gy to the breast/ASA is a safe and effective therapy for patients treated with conservative surgery. The risk of carcinogenesis is low. Positive surgical margins, extracapsular node invasion, and HER2-enriched/triple-negative phenotypes appear as a cluster of features linked with a higher risk for locoregional relapse. [ABSTRACT FROM AUTHOR]

Purpose: To report patients' quality of life (QoL) at 1 year in a phase 2 randomized trial comparing partial breast irradiation (PBI) with whole-breast irradiation (WBI) after breast-conserving surgery (BCS) for breast cancer. Methods: Women aged ≥ 45 years with low-risk breast cancer after BCS were randomly assigned (1:1) to receive PBI (40 Gy in 10 fractions over 2 weeks) or WBI (43.5 Gy in 15 fractions over 3 weeks). The primary endpoint—the incidence of toxicities of grade 2 or higher—will be reported when participants complete 5 years of follow-up. QoL was assessed at baseline (T0), at the end of radiotherapy (RT) (T1), 6 months (T2) and 1 year (T3) after RT by using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. We calculated the scores for all QOL subscales and differences in mean scores were compared. This study was registered at ClinicalTrials.gov (NCT03583619). Results: Between June 2017 and January 2019, 140 women were randomly assigned to receive PBI or WBI (n = 70 per group). Fifty-nine and 56 patients treated with PBI and WBI, respectively, were eligible for the QoL analysis. There were no significant differences in any subscale scores at T0, T1, T2, or T3 between the PBI and WBI arms. The scores for most QoL subscales that were influenced by RT recovered to a similar or better level relative to T0 scores within 1 year after RT, except for the scores of the dyspnea subscale. Longitudinal analysis showed that time since RT had a significant impact on physical functioning, role functioning, social functioning, fatigue, pain, dyspnea, financial difficulties, body image, and breast and arm symptoms. Conclusion: PBI using the intensity-modulated RT affords QoL comparable to that provided by WBI. Most QoL subscale scores that were influenced by RT recovered to a similar or better level relative to baseline scores within 1 year after RT. [ABSTRACT FROM AUTHOR]

Purpose: To use cone-beam computed tomography (CBCT) imaging to determine the impacts of patient characteristics on the magnitude of geometric setup errors and obtain patient-specific planning target volume (PTV) margins from the correlated patient characteristics in whole breast irradiation (WBI).Methods: Between January 2019 and December 2019, a total of 97 patients who underwent breast-conserving surgery, followed by intensity-modulated radiation therapy in WBI, were scanned with pre-treatment CBCT for the first three treatment fractions and weekly for the subsequent fractions. Setup errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions were recorded and analyzed with patient characteristics-including age, tumor location, body mass index (BMI), chest circumference (CC) and breast volume (BV)-to examine the predictors for setup errors and obtain specific PTV margins.Results: A total of 679 CBCT images from 97 patients were acquired for analysis. The mean setup errors for the whole group were 2.32 ± 1.21 mm, 3.71 ± 2.21 mm and 2.75 ± 1.56 mm in the LR, SI and AP directions, respectively. Patients' BMI, CC and BV were moderately associated with setup errors, especially in the SI directions (R = 0.40, 0.43 and 0.22, respectively). Setup errors in the SI directions for patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.56 ± 2.59 mm, 4.77 ± 2.42 mm and 4.30 ± 2.43 mm, respectively, which were significantly greater than those of patients with BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3 (P < 0.05). Correspondingly, the calculated PTV margins in patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.25/7.95/4.93 mm, 4.37/7.66/5.24 mm and 4.22/7.54/5.29 mm in the LR/SI/AP directions, respectively, compared with 3.64/4.64/5.09 mm, 3.31/4.50/4.82 mm and 3.29/5.74/4.73 mm for BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3, respectively.Conclusions: The magnitude of geometric setup errors was moderately correlated with BMI, CC and BV. It was recommended to set patient-specific PTV margins according to patient characteristics in the absence of daily image-guided treatment setup. [ABSTRACT FROM AUTHOR]

Background: Data are lacking about the benefit of adjuvant endocrine therapy (ET) in older patients with multiple comorbidities. The authors sought to determine the effect of ET on the survival of older patients who had multiple comorbidities and estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, pathologic node-negative (pN0) breast cancer.Methods: Women aged ≥70 years in the National Cancer Database (2010-2014) with Charlson/Deyo comorbidity scores of 2 or 3 who had pathologic tumor (pT1)-pT3/pN0, ER-positive/HER2-negative breast cancer were divided into 2 cohorts: adjuvant ET and no ET. Propensity scores were used to match patients based on age, comorbidity score, facility type, pT classification, chemotherapy, surgery, and radiation therapy. A Cox proportional hazards model was used to estimate the effect of ET on overall survival (OS).Results: In the nonmatched cohort (n = 3716), 72.8% of patients received ET (n = 2705), and 27.2% did not (n = 1011). The patients who received ET were younger (mean age, 76 vs 79 years; P < .001) and had higher rates of breast conservation compared with those who did not receive ET (lumpectomy plus radiation: 43.4% vs 23.8%, respectively; P < .001). In the matched cohort (n = 1972), the median OS was higher in the ET group (79.2 vs 67.7 months; P < .0001). In the adjusted analysis, ET was associated with improved survival (hazard ratio, 0.70; 95% CI, 0.59-0.83).Conclusions: In older patients who have pN0, ER-positive/HER2-negative breast cancer with comorbidities, adjuvant ET was associated with improved OS, which may have been overestimated given the confounders inherent in observational studies. To optimize outcomes in these patients, current standard recommendations should be considered stage-for-stage based on life expectancy and the level of tolerance to treatment. [ABSTRACT FROM AUTHOR]

Modern neoadjuvant systemic therapy (NST) can result in high pathologic complete response rates (pCR) in triple negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) breast cancer. The role of surgery is, therefore, being reconsidered in this rapidly evolving field. This report presents oncological outcomes of seven patients with TN or HER2+ breast cancer, with exceptional response to NST, and a post-NST image-guided vacuum assisted biopsy showing no residual disease (ypT0), who opted not to have breast surgery. The median age was 49 (IQR 36–61) years and the median tumour size at diagnosis was 50 (IQR 16–65) mm. All patients received breast radiotherapy and continued adjuvant systemic therapies as appropriate. At a median follow-up of 67 (IQR 61–77) months, all patients were alive and free of disease. This small case series supports the need for further research in 'exceptional responders' to provide safe, individualized patient-centred care. [ABSTRACT FROM AUTHOR]

Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution. Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT. A total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40–78), the median tumor size was 1.1 cm (range: 0.2–3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4–14) were used. For APBI, the median CTV and V 100 were 40.8 cc (range: 8.6–99) and 35.4 cc (range: 7.2–94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3–28 %) and the median local treatment duration was 10 days (range: 7–16). With a median follow-up of 8.8 years (range: 0.3–16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %. IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose). Methods: A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient's grade of satisfaction with cosmetic outcomes. Results: Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10–16 years). The cumulative risk of IBTR at 5–10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5–10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months' follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p < 0.05). No late complications associated with IOERT were observed. The overall cosmetic results were scored as good or excellent in physician and patient evaluations for both IOERT and EBRT. There were significantly better scores for IOERT at all time points in physician and patient evaluations with the greatest difference at the end of EBRT (p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis). Conclusion: A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years. [ABSTRACT FROM AUTHOR]

Background: Louisiana has the third highest breast cancer mortality in the US, despite ranking 30th in incidence. Whether surgical approach contributes to such a poor outcome is unknown. We compared outcomes of breast-conserving surgery plus radiation (BCT) vs mastectomy (MST) for Louisiana women with early-stage breast cancer.Study Design: Data on women diagnosed with Stage I-II breast cancer from 2004 to 2016 were analyzed from the Louisiana Tumor Registry. Overall survival (OS) and breast cancer-specific survival (CSS) were compared between BCT and MST. Kaplan-Meier method and log-rank test were used to compare survival curves, and logistic regression was used to examine the association of sociodemographic and clinical factors with the type of breast cancer surgery. Values of p < 0.05 were considered significant.Results: Of the 18,260 patients, 9,968 patients (54.6%) had BCT and 8,292 patients (45.4%) had MST. Compared with BCT, the MST group tended to be underinsured/Medicare/Medicaid, more impoverished, had higher stage 2 disease, were more likely to reside in rural regions, travel ≥25 miles to radiation treatment facility, be treated at low volume centers, and have T3, node positive, and poorly differentiated tumors. Ten-year OS and CSS were significantly better among those who had BCT (OS: 80.0%; 95% CI: 79.0%-81.1%; CSS: 92.7%; 95% CI: 92.1%-93.4%) than those having MST (OS: 69.3%; 95% CI: 68.0%-70.5%; CSS: 88.8%:95% CI: 87.9%-89.7%) (p < 0.05). Even after controlling for sociodemographic and clinical variables, MST was associated with a 28.6% increased risk of death from all causes (hazard ratio [HR]:1.286; 95% CI:1.197-1.380) and a 29.8% increased risk of breast-cancer specific death (HR:1.298; 95% CI: 1.150-1.465).Conclusions: Surgical approach, a factor that is within the control of the surgeon, has an impact on mortality for Louisiana women with early-stage breast cancer. [ABSTRACT FROM AUTHOR]

To analyze contemporary practice patterns in breast cancer radiotherapy (RT) and to assess longitudinal changes therein over 5 years in Korea. A nationwide survey was conducted among board-certified radiation oncologists in Korea by the Division for Breast Cancer of the Korean Radiation Oncology Group in March 2022. The survey consisted of 44 questions related to six domains: hypofractionated (HypoFx) whole breast RT, accelerated partial breast RT (APBI), regional nodal irradiation (RNI), RT for ductal carcinoma in situ (DCIS), postmastectomy RT (PMRT), and tumor bed boost. In total, 70 radiation oncologists from 61 of 101 (60%) institutions participated in the survey. HypoFx RT was used by 62 respondents (89%), which has significantly increased from 36% in 2017. The HypoFx RT was commonly administered at 40–42.5 Gy in 15–16 fractions. APBI was used by 12 respondents (17%), which has increased from 5% in 2017. The use of RNI did not change significantly: ≥ pN2 (6%), ≥ pN1 (33%), and ≥ pN1 with pathological risk factors (61%). However, the indications for use of internal mammary lymph node (IMN) irradiation have expanded. In particular, the rates of routine treatment of IMN (11% from 6% in 2017) and treatment in cases of ≥ pN2 (27% from 14% in 2017) have doubled; however, the rate of treatment for only IMN involvement, identified on imaging, has decreased to 31% from 47% in 2017. With regard to DCIS, the use of hypoFx RT increased to 75% from 25%, and the rate of omission on of RT after breast-conserving surgery decreased to 38% from 48% in 2017. The use of hypoFx RT for PMRT also increased to 36% from 8% in 2017. The adoption of HypoFx RT after breast-conserving surgery in invasive breast cancer and DCIS has increased significantly, whereas that for PMRT has increased moderately, compared to 2017. Further studies are required to determine the optimal use of RNI. [ABSTRACT FROM AUTHOR]

Background and Purpose: The use of external beam accelerated partial breast irradiation (APBI) using a twice-per-day regimen has raised concerns about increase rates of late toxicities. We compared toxicity outcomes of external beam APBI using a once-per-day regimen and accelerated hypofractionated whole breast irradiation (AWBI) in patients with early-stage breast cancer. Materials and Methods: This was a single-institution, retrospective cohort study. Patients aged ≥50 years with pTisN0 or pT1N0 breast cancer who underwent breast-conserving surgery and adjuvant radiotherapy were included. APBI was delivered at 38.5 Gy in 10 fractions once daily using magnetic resonance imaging (MRI)-guided radiotherapy only to patients who were strictly "suitable", according to the ASTRO-APBI guidelines. AWBI was delivered at 40.5–43.2 Gy in 15 or 16 fractions with or without a boost. Results: Between October 2015 and December 2018, 173 and 300 patients underwent APBI and AWBI, respectively. At a median follow-up of 34.9 months (range 7.1 to 55.4 months), the 3-year recurrence-free survival rates of the APBI and AWBI groups were both 99.2% (p=0.63). Acute toxicities were less frequent in the APBI than AWBI group (grade 1: 95 [54.9%] vs. 233 [77.7%] patients; grade 2: 7 [4.0%] vs. 44 [14.7%] patients; no grade ≥3 toxicities were observed in either group, p<0.001). Late toxicities were less common in the APBI than AWBI group (grade 1: 112 [64.7%] vs. 197 [65.7%] patients; grade 2: 9 [5.2%] vs. 64 [21.3%] patients; grade 3: 0 vs. 5 [1.7%] patients, p<0.001). Multivariate analysis showed that APBI was significantly associated with fewer late toxicities of grade ≥2 compared with AWBI (odds ratio 4.17, p=0.006). Conclusion: Once-per-day APBI afforded excellent locoregional control and fewer toxicities compared with AWBI. This scheme could be an attractive alternative to AWBI in patients who meet the ASTRO-APBI guidelines. [ABSTRACT FROM AUTHOR]