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.

Brachytherapy Department Centrum Onkologii Instytut im Marii Skłodowskiej Warsaw Poland

Brachytherapy Department Centrum Onkologii Instytut im Marii Skłodowskiej Warsaw Poland; Podkarpacki Hospital Cancer Center Brzozów Brzozów Poland

Center of Radiotherapy National Institute of Oncology Budapest Hungary

Department of Medical Informatics Biometry and Epidemiology University Erlangen Nuremberg Erlangen Germany

Department of Radiation Oncology Catalan Institute of Oncology Barcelona Spain

Department of Radiation Oncology Clemens Hospital Münster Germany

Department of Radiation Oncology Hospital Barmherzige Brüder Regensburg Germany

Department of Radiation Oncology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Radiation Oncology University Hospital AKH Wien Vienna Austria

Department of Radiation Oncology University Hospital Bern Inselspital Switzerland

Department of Radiation Oncology University Hospital Erlangen Erlangen Germany

Department of Radiation Oncology University Hospital Erlangen Erlangen Germany; Department of Radiation Oncology University Hospital Rostock Rostock Germany

Department of Radiation Oncology University Hospital Kiel Kiel Germany

Department of Radiation Oncology University Hospital Kiel Kiel Germany; Department of Radiotherapy Sana Hospital Offenbach Offenbach Germany

Department of Radiation Oncology University Hospital Leipzig Leipzig Germany

Department of Radiation Oncology University Hospital Leipzig Leipzig Germany; Department of Radiation Oncology University Hospital Rostock Rostock Germany

Department of Radiation Oncology University Hospital Rostock Rostock Germany

Department of Radiation Oncology University Hospital Würzburg Würzburg Germany

Department of Radiation Oncology Valencian Institute of Oncology Valencia Spain

Interdisciplinary Brachytherapy Unit University of Lübeck Universitätsklinikum Schleswig Holstein Campus Lübeck Lübeck Germany

Lancet Oncol. 2017 Feb;18(2):168-169. doi: 10.1016/S1470-2045(17)30001-3. PubMed

References provided by Crossref.org

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Toxicity of external beam accelerated partial-breast irradiation (APBI) in adjuvant therapy of early-stage breast cancer: prospective randomized study

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ClinicalTrials.gov
NCT00402519