Background and purpose:Clinical trials on ultrahypofractionated (UHF) whole‑breast radiotherapy demonstrated non‑inferiority to moderate hypofractionation (HF). However, real-world evidence using modern treatment techniques, captured by fully automated electronic patient-reported outcome measures (ePROM), remains limited. This study prospectively evaluated the clinical implementation of UHF whole-breast radiotherapy using intensity-modulated/volumetric arc radiotherapy (IMRT/VMAT) with ePROM-based adverse event monitoring. Materials and methods:In this single-centre prospective cohort, consecutive non-metastatic breast cancer patients (breast conserving surgery, no nodal and no boost irradiation) received either HF (15 × 2.67  Gy) or UHF (5 × 5.2  Gy). Acute and late side effects were assessed using PRO‑CTCAE items (itching, radiation skin reaction, skin darkening, pain and breast tenderness) via an automated ePROM platform at the first and last fraction, and at 3, 6, 9, 12, and 24  months. Longitudinal adverse event grades were modelled using population-averaged ordinal generalised estimating equations adjusted for age, surgery, and hormone therapy. Results:The patient cohort of 308 patients included 177 UHF and 131 HF patients. ePROM completion adherence was high (30% drop-out at 24 months). No clinically meaningful differences in adverse event severity were observed between both regimens, except for higher radiation skin reactions at the last fraction in HF (odd ratio (OR) = 2.70). At 24 months, only pain severity differed, with higher odds for HF (OR = 3.08). Other endpoints showed no significant between-group differences. Conclusion:UHF whole-breast radiotherapy delivered with contemporary IMRT/VMAT showed no increase in acute or late patient-reported adverse events compared with HF, confirming its safe integration into clinical routine.

Purpose: Male breast cancer (maleBC) is an orphan disease. Aside from age, risk factors include genetic mutations and conditions like Klinefelter syndrome or other reasons of hypogonadism. Treatment is based on standards in women, but biological differences may exist, with maleBC exhibiting higher rates of hormone-receptor expression. Limiting data exists regarding the rate of low/ultralow HER2 expression, a predictive biomarker for the antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in HER2-negative disease in women. Materials and Methods: We conducted a retrospective single-center analysis of clinicopathological features of maleBC at a tertiary cancer center. We identified a cohort of 57 maleBC patients, described demographic, pathological, prognostic and surgical and systemic treatment data and evaluated frequencies of low and ultralow HER2 expression. Results: The mean age was 64.3 (SE ± 1.79) years; 94.7% (n = 54) of patients presented with early/nonmetastatic breast cancer and 40.7% (22 of 54) of patients exhibited nodal involvement. Most patients (92.6%, 50 of 54 patients) had luminal disease and approximately one third of patients received chemotherapy. Endocrine therapy was administered in 87.7% (n = 50/57) of cases. For 52 of the patients included, full receptor status data including HER2 IHC scoring and/or histological specimens were available. IHC slides of tumor specimens from 24 patients with either historically reported “HER2 negative” or “HER2 0” expression were available for reassessment; 79.2% (n = 19 of 24) of these tumors exhibited either HER2-low or -ultralow expression. In the whole cohort, rates of HER2-low and -ultralow expression were 75.0% (39 of 52) and 5.8% (3 of 52 patients), respectively. The median follow-up was 7 years. Six deaths occurred in the total population (n = 57). The median event-free survival (EFS) was 8.39 years (95% CI 7.36–11.35). No statistically significant associations were observed between HER2 expression categories and clinicopathological variables including grade, ER status, nodal status, genetic variant status, age, Ki67 index, or overall survival events. Conclusions: In this cohort of maleBC patients, high rates of combined HER2-low and -ultralow expression were observed upon reassessment of tumors with historically negative HER2 status, shedding light on potential ADC eligibility in male breast cancer.

Radiotherapy is an integral part of multidisciplinary adjuvant treatment for early breast cancer and is recommended in a high percentage of patients following breast-conserving surgery or mastectomy, particularly those with specific risk factors. Due to diagnostic and clinical developments, tumour characteristics and the risk of relapse can now be assessed more precisely, putting the era of ‘one-size-fits-all’ radiotherapy treatments behind us. Consideration of all the advantages and disadvantages of breast radiotherapy, including acute and long-term side effects, makes risk-adapted and tailored treatment necessary. Continuous technical improvements allow better dose distribution in the target and better sparing of organs at risk with a possible de-escalation in treatment time with moderate and ultrahypofractionation. Incorporating molecular markers for better estimation of the local recurrence risk facilitates decision-making for the use of partial breast irradiation or even the complete omission of irradiation. In this short review, modern strategies of de-escalation in early breast radiotherapy are discussed without a claim of completeness and reflects the personal choice of the author.

Purpose: To investigate the sensitivity of patient-reported outcome measures (PROMs) to detect treatment-related side effects in patients with breast cancer undergoing external beam photon radiotherapy.Methods: As part of daily clinical care, an in-house developed PROM tool was used to assess side effects in patients during a) whole-breast irradiation (WBI) to 40 Gy, b) WBI with a sequential boost of 10 Gy, and c) partialbreast irradiation (PBI) to 40 Gy.Results: 414 patients participated in this prospective study between October 2020 and January 2022, with 128 patients (31 %) receiving WBI, 241 (58 %) receiving WBI followed by a sequential boost, and 50 patients (12 %) receiving PBI. Significant differences in the reported toxicities (itching, radiation skin reaction, skin darkening, and tenderness and swelling) were reported between the WBI cohorts with and without boost (p < 0.001, p < 0.001, p < 0.001, and p = 0.002, respectively). The comparison of PBI with WBI (no-boost) yielded significant differences for radiation skin reaction (p < 0.001). Conclusion: The results highlight the high sensitivity of PROMs to detect treatment-related side effects in patients with breast cancer. Thus, PROMs may be a valuable tool for quality control and may support evidence-based learning from real-world data originating from daily routine care.

Purpose To investigate the feasibility of a thermo-optical surface imaging (SGRT) system combined with room-based stereoscopic X‑ray image guidance (IGRT) in a dedicated breast deep inspiration breath-hold (DIBH) irradiation workflow. In this context, benchmarking of portal imaging (EPID) and cone-beam CT (CBCT) against stereoscopic X‑rays was performed. Methods SGRT + IGRT data of 30 left-sided DIBH breast patients (1 patient with bilateral cancer) treated in 351 fractions using thermo-optical surface imaging and X-ray IGRT were retrospectively analysed. Patients were prepositioned based on a free-breathing surface reference derived from a CT scan. Once the DIBH was reached using visual feedback, two stereoscopic X‑ray images were acquired and registered to the digitally reconstructed radiographs derived from the DIBH CT. Based on this registration, a couch correction was performed. Positioning and monitoring by surface and X-ray imaging were verified by protocol-based EPID or CBCT imaging at selected fractions and the calculation of residual geometric deviations. Results The median X‑ray-derived couch correction vector was 4.9 (interquartile range [IQR] 3.3–7.1) mm long. Verification imaging was performed for 134 fractions (216 RT field verifications) with EPID and for 37 fractions with CBCT, respectively. The median 2D/3D deviation vector length over all verification images was 2.5 (IQR 1.6–3.9) mm/3.4 (IQR 2.2–4.8) mm for EPID/CBCT, both being well within the planning target volume (PTV) margins (7 mm). A moderate correlation (0.49–0.65) was observed between the surface signal and X-ray position in DIBH. Conclusion DIBH treatments using thermo-optical SGRT and X-ray IGRT were feasible for breast cancer patients. Stereoscopic X‑ray positioning was successfully verified by standard IGRT techniques.

Purpose To evaluate efficacy results of the GEC-ESTRO phase III non-inferiority trial in subgroups of patients defined by the ASTRO criteria for patient selection for APBI. Methods Patients aged ≥40 years with low risk invasive breast cancer or ductal carcinoma in-situ after breast conserving surgery were randomized to receive either 50 Gy WBI with tumor bed boost of 10 Gy or APBI using multicatheter brachytherapy. 633/1184 patients were randomized to APBI using multicatheter brachytherapy. In the context of the current available complete results after 10 years follow-up, we report results of an additional sub-analysis of these latter 633 patients regarding 10-year local control rates, disease-free and overall survival results comparing sub-groups categorized according to ASTRO criteria for patient selection for APBI. The trial is registered with ClinicalTrials.gov, NCT00402519. Results We recorded the 10-year local recurrence rate in the APBI arm in the value of 3.5%, which is one of lowest 10y.-local recurrence rates among all other published phase 3 trials. Among 633 patients treated with sole multicatheter brachytherapy for APBI, according to ASTRO criteria altogether 423 patients (66.8%) were classified as "suitable", 195 (30.8%) as "cautionary" and 11 (1.7%) as "unsuitable"; in 4 cases no ASTRO categorization was possible. In the "suitable" and "cautionary" groups, resp., the cumulative incidence (95% CI) of local recurrence at 10 years was 3.29% (1.44-5.13%) and 5.03% (1.8-8.27%), respectively (p=0.612). 10-year disease-free survival was 81.91% (78.1-85.9%) and 83.63% (78.31-89.32%), respectively (p=0.63). 10-year overall survival was 88.26% (85.07-91.57%) and 95.04% (91.92-98.27%), respectively (p=0.02). Conclusion The 10-year results are comparable in patients treated with breast conserving surgery followed by APBI using multicatheter brachytherapy in "suitable" and "cautionary" risk groups' according to ASTRO criteria. As a consequence we believe that in due time, a careful retrial of current ASTRO selection criteria for APBI should be considered. To evaluate efficacy results of the GEC-ESTRO phase III non-inferiority trial in subgroups of patients defined by the ASTRO criteria for patient selection for APBI. Patients aged ≥40 years with low risk invasive breast cancer or ductal carcinoma in-situ after breast conserving surgery were randomized to receive either 50 Gy WBI with tumor bed boost of 10 Gy or APBI using multicatheter brachytherapy. 633/1184 patients were randomized to APBI using multicatheter brachytherapy. In the context of the current available complete results after 10 years follow-up, we report results of an additional sub-analysis of these latter 633 patients regarding 10-year local control rates, disease-free and overall survival results comparing sub-groups categorized according to ASTRO criteria for patient selection for APBI. The trial is registered with ClinicalTrials.gov, NCT00402519. We recorded the 10-year local recurrence rate in the APBI arm in the value of 3.5%, which is one of lowest 10y.-local recurrence rates among all other published phase 3 trials. Among 633 patients treated with sole multicatheter brachytherapy for APBI, according to ASTRO criteria altogether 423 patients (66.8%) were classified as "suitable", 195 (30.8%) as "cautionary" and 11 (1.7%) as "unsuitable"; in 4 cases no ASTRO categorization was possible. In the "suitable" and "cautionary" groups, resp., the cumulative incidence (95% CI) of local recurrence at 10 years was 3.29% (1.44-5.13%) and 5.03% (1.8-8.27%), respectively (p=0.612). 10-year disease-free survival was 81.91% (78.1-85.9%) and 83.63% (78.31-89.32%), respectively (p=0.63). 10-year overall survival was 88.26% (85.07-91.57%) and 95.04% (91.92-98.27%), respectively (p=0.02). The 10-year results are comparable in patients treated with breast conserving surgery followed by APBI using multicatheter brachytherapy in "suitable" and "cautionary" risk groups' according to ASTRO criteria. As a consequence we believe that in due time, a careful retrial of current ASTRO selection criteria for APBI should be considered.

BACKGROUND: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. METHODS: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. FINDINGS: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. INTERPRETATION: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. FUNDING:German Cancer Aid, Germany.

AIM:Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario.METHODS:A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology.RESULTS:The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR.CONCLUSIONS:The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.

BackgroundPrevious results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life.MethodsWe did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0–IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking …

Background Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was noninferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. Methods We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins >= 2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials. gov, number NCT00402519. Findings Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up.Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65.5 (SD 20.6) versus whole-breast irradiation group 64.6 (19.6), p=0.37; at 5 years, APBI group 66.2 (22.2) versus whole-breast irradiation group 66.0 (21.8), p=0.94.The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale.Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13.6, 95% CI 9.7-17.5; p<0.0001) and at 3-month follow-up (difference of means 12.7, 95% CI 9.8-15.6; p<0.0001). Interpretation APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation.This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. Copyright (c) 2018 Elsevier Ltd.All rights reserved.

Radiotherapy plays an important part in the management of breast cancer. Especially after breast-conserving surgery, external whole breast irradiation, occasionally with an additional local boost, is an integral part of breast conservation. Besides external radiation techniques, brachytherapy (BT) has long been among the treatment options, especially with regard to local boost application. With the emerging implementation of accelerated partial breast irradiation (APBI), BT in general and interstitial multi-catheter BT in particular, are gaining an increasing role in the management of a selected group of early breast cancer patients. APBI is an approach to reduce the irradiated area to the former tumor bed rather than treating the whole breast tissue in patients with a low baseline local recurrence risk. After a variety of phase I-III clinical studies, it is clearly evident that APBI will play a role in the treatment of this selected patient group. In this review, we focus on the clinical development and different available techniques of breast BT and provide a preview of prospects for its use. (C) 2018 S. Karger GmbH, Freiburg

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

Background and purposeTo compare early side effects and patient compliance of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy to external beam whole breast irradiation (WBI) in a low-risk group of patients with breast cancer.Material and methodsBetween April 2004 and July 2009, 1328 patients with UICC stage 0–IIA breast cancer were randomized to receive WBI with 50Gy and a boost of 10Gy or APBI with either 32.0Gy/8 fractions, or 30.1Gy/7 fractions (HDR-brachytherapy), or 50Gy/0.60–0.80Gy per pulse (PDR-brachytherapy). This report focuses on early side-effects and patient compliance observed in 1186 analyzable patients. ClinicalTrials.gov identifier: NCT00402519.ResultsPatient compliance was excellent in both arms. Both WBI and APBI were well tolerated with moderate early side-effects. No grade 4 toxicity had been observed. Grade 3 side effects were exclusively seen for early skin toxicity (radiation dermatitis) with 7% vs. 0.2% (p<0.0001), and breast infection with 0% vs. 0.2% (p=n.s.) for patients treated with WBI and APBI. The incidence of grades 1–2 early side effects for WBI and APBI was 86% vs. 21% (p<0.0001) for skin toxicity, 2% vs. 20% (p<0.0001) for mild hematoma, and 2% vs. 5% (p=0.01) for mild breast infection rates, respectively. No differences had been found regarding grades 1–2 early breast pain (26% vs. 29%, p=0.23).ConclusionsAPBI with interstitial multicatheter brachytherapy was tolerated very well and dramatically reduced early skin toxicity in comparison to standard WBI.

To evaluate efficacy results of the GEC-ESTRO phase III non-inferiority trial in subgroups of patients defined by the ASTRO and GEC-ESTRO criteria for patient selection for APBI. Patients aged ≥40 years with low risk invasive breast cancer and ductal carcinoma in-situ after BCS were randomized to receive either 50 Gy WBI with tumor bed boost of 10 Gy or APBI using multicatheter brachytherapy. 633/1083 patients were randomized to APBI using multicatheter brachytherapy. We report a sub-analysis of these latter 633 patients regarding 5-year local control rates, disease-free and overall survival results comparing subgroups categorized according to ASTRO and GEC-ESTRO criteria for patient selection for APBI. The trial is registered with ClinicalTrials.gov, NCT00402519. Among 633 patients treated with sole multicatheter brachytherapy for APBI, 430 patients (68%) were classified according to GEC-ESTRO criteria as good candidates for APBI - "low risk group", 203 (32%) as possible candidates for APBI - "intermediate risk group" and no patient was in the "high risk group". According to ASTRO criteria, 247 patients (39%) classified as "suitable", 287 (45%) as "cautionary" and 98 (16%) as "unsuitable". Using ESTRO criteria for subgrouping of patients, the cumulative incidence of local recurrence at 5 years was 1.18% versus 2% (p=0.42) in the "low risk group" and "intermediate risk group", respectively. Furthermore 5-year disease-free survival was 94.6% versus 96% (p = 0.49) and 5-year overall survival was 96.7% versus 98.5% (p = 0.25) in the "low risk group" and "intermediate risk group", respectively. Using ASTRO criteria for subgrouping of patients, the cumulative incidence of local recurrence at 5 years was 2.04%, 1.05% and 1.05% in the "suitable", "cautionary" and "unsuitable" groups (p=0.6), respectively. 5-year disease-free survival was 94.3%, 95.1% and 96.8% in the "suitable", "cautionary" and "unsuitable" groups (p=0.63), respectively. 5-year overall survival was 96.7%, 97.2% and 99.0% in the "suitable", "cautionary" and "unsuitable" groups (p = 0.53), respectively. However, it should be pointed out that due to the hitherto low number of events, statistical power and precision, respectively, to identify differences between subgroups is limited. The 5-year results are similar in patients treated with breast conserving surgery followed by APBI using multicatheter brachytherapy in "low risk group" and "intermediate risk group" according to GEC-ESTRO criteria and in all risk groups' according to ASTRO criteria. As a consequence, we believe that in due time, a careful revision of current ASTRO and ESTRO selection criteria for APBI should be discussed.

The 5-year survival results of the GEC-ESTRO APBI trial have been reported recently. In this analysis we report the 5-year incidences of late toxicities and cosmetic results of patients treated with APBI using multi-catheter brachytherapy (BT) compared to those who underwent whole breast irradiation (WBI). Between 2004 and 2009, 1184 eligible patients aged ≥40 years with stage 0-IIA breast cancer who underwent breast conserving surgery (BCS) were randomly assigned to receive either 50 Gy WBI with tumor bed boost of 10 Gy or APBI using HDR/PDR multi-catheter BT. Among these, 5-year follow-up records (with a time window between 4 and 6 years) on late toxicities and cosmetic results were available for 942 patients (80%). Five-year incidences of late toxicities scored by the RTOG/EORTC scheme were compared using Fisher’s exact test. Five-year rates of skin and soft tissue toxicities were estimated in terms of cumulative incidences. Cosmetic results were scored by both patients and treating radiation oncologists before RT and annually thereafter. The prevalence of grade (G) 2-3 late skin toxicity at 5 years was 3.7% in the APBI group vs. 6.1% in the WBI group (p=0.06). The 5-year rate of ≥G2 skin toxicity was 6.71% (95%CI: 4.67-8.75%) after APBI, and 10.5% (95%CI: 7.78-13.1%) after WBI. The frequency of any (G1-3) skin pigmentation was 5.7% vs. 10.0%, respectively (p=0.009). The 5-year rate of ≥G2 skin pigmentation was 2.94% (95%CI: 1.60-4.28%) after APBI, and 7.33% (95%CI: 5.08-9.57%) after WBI. Concerning G2-3 late subcutaneous tissue side effects, the prevalence was 6.2% in the APBI group vs. 5.4% in the WBI group (p=0.33). The 5-year rate of ≥G2 soft tissue toxicity was 11.4% (95%CI: 8.82-14.0%) after APBI, and 9.60% (95%CI: 7.01-12.2%) after WBI. The respective frequency of symptomatic fat necrosis was 1.2% vs. 0.9% (p=0.49). Neither APBI nor WBI deteriorated baseline cosmetic appearance over time. The prevalence of G2-3 breast pain was low in both arms (0.6% after APBI; 1.6% after WBI; p=0.11).The rate of excellent/good cosmetic results judged by the patients was 92.2% vs. 91.1% (p=0.57) in the APBI and WBI group, and 92.7% vs. 90.0% (p=0.14) scored by the physicians. However, more patients experienced excellent cosmetic results after APBI compared to WBI either rated by the patients (43.6% vs. 30.9%; p=0.00002) or the physicians (39.7% vs. 30.7%; p<0.002). The 5-year toxicity profile and cosmetic results are similar in patients treated with BCS followed by either APBI using multi-catheter BT or WBI. Significantly less late skin side effects and a trend towards better cosmetic results have been observed in the APBI arm.

BACKGROUND:In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results.METHODS:We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519.FINDINGS:Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1.44% (95% CI 0.51-2.38) with APBI and 0.92% (0.12-1.73) with whole-breast irradiation (difference 0.52%, 95% CI -0.72 to 1.75; p=0.42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0.08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46).INTERPRETATION:The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival.FUNDING:German Cancer Aid.

OBJECTIVE:The aim was to develop a delineation guideline for target definition for APBI or boost by consensus of the Breast Working Group of GEC-ESTRO.PROPOSED RECOMMENDATIONS:Appropriate delineation of CTV (PTV) with low inter- and intra-observer variability in clinical practice is complex and needs various steps as: (1) Detailed knowledge of primary surgical procedure, of all details of pathology, as well as of preoperative imaging. (2) Definition of tumour localization before breast conserving surgery inside the breast and translation of this information in the postoperative CT imaging data set. (3) Calculation of the size of total safety margins. The size should be at least 2 cm. (4) Definition of the target. (5) Delineation of the target according to defined rules.CONCLUSION:Providing guidelines based on the consensus of a group of experts should make it possible to achieve a reproducible and consistent definition of CTV (PTV) for Accelerated Partial Breast Irradiation (APBI) or boost irradiation after breast conserving closed cavity surgery, and helps to define it after selected cases of oncoplastic surgery.

PURPOSE: To evaluate accelerated partial breast irradiation (APBI) in patients after oncoplastic surgery for early breast cancer.METHODS AND MATERIALS: A retrospective analysis of 136 breasts of 134 patients, who received breast-conserving oncoplastic surgery for low-risk breast cancer between 2002 and 2010 in the Universities of Vienna and Luebeck followed by adjuvant APBI applying total doses of pulse dose rate of 50.4 Gy or high-dose rate (HDR) of 32 Gy over 4 days. Target volume definition was performed by the use of surgical-free margin data, related to intraoperatively fixed clip positions, pre- and postoperative imaging, and palpation.RESULTS: At the time of data acquisition, 131 of 134 patients were alive. The median follow-up time was 39 months (range, 4-106 months). After high-dose rate treatment, 3 of 89 patients showed systemic progress after a mean follow-up of 47 months (range, 19-75 months) and 2 patients had a different quadrant in-breast tumor after 27 and 35 months. One patient died 7 months after treatment of unknown causes. After pulse dose rate treatment, 1 of 45 patients had a local recurrence after 42 months and 1 patient died because of another cause after 13 months. We observed mild fibrosis in 27 breasts, telangiectasia in 6, hyperpigmentation in 14 cases, and keloid formation in 1.CONCLUSIONS: These preliminary results suggest the feasibility of multicatheter APBI after oncoplastic breast-conserving surgery in selected low-risk breast cancer patients; however, special attention to target volume definition is needed. Further prospective investigations with long followup are needed to define the real value of the procedure. (C) 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.