SummaryBackgroundLocal cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy.MethodsIMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1–3, with a tumour size of 3 cm or less (pT1–2), none to three positive axillary nodes (pN0–1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase [non-inferiority margin] at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio [HR] was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634.FindingsBetween May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7–83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5–2·3) of patients in the control group, 0·2% (0·02–1·2) in the reduced-dose group, and 0·5% (0·2–1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were −0·73% (−0·99 to 0·22) for the reduced-dose and −0·38% (−0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the ...

PURPOSE Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHODS Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 fr of 6.0 or 5.7 Gy (1 week). The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULTS A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

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Background Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer. MethodsSUPREMO is an open-label, international, parallel-group, randomised, controlled trial. Women aged 18 years or older with intermediate-risk breast cancer (defined as pT1-2N1; pT3N0; or pT2N0 if also grade III or with lymphovascular invasion) who had undergone mastectomy and, if node positive, axillary surgery, were randomly assigned (1:1) to receive chest wall radiotherapy (50 Gy in 25 fractions or a radiobiologically equivalent dose of 45 Gy in 20 fractions or 40 Gy in 15 fractions) or no radiotherapy. Randomisation was done with permuted blocks of varying block length, and stratified by centre, without masking of patients or investigators. The primary endpoint is 10-year overall survival. Here, we present 2-year results of QOL (a prespecified secondary endpoint). The QOL substudy, open to all UK patients, consists of questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23, Body Image Scale, Hospital Anxiety and Depression Scale [HADS], and EQ-5D-3L) completed before randomisation, and at 1, 2, 5, and 10 years. The prespecified primary outcomes within this QOL substudy were global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, and anxiety and depression. Data were analysed by intention to treat, using repeated mixed-effects methods. This trial is registered with the ISRCTN registry, number ISRCTN61145589.Findings Between Aug 4, 2006, and April 29, 2013, 1688 patients were enrolled internationally and randomly assigned to receive chest wall radiotherapy (n=853) or not (n=835). 989 (79%) of 1258 patients from 111 UK centres consented to participate in the QOL substudy (487 in the radiotherapy group and 502 in the no radiotherapy group), of whom 947 (96%) returned the baseline questionnaires and were included in the analysis (radiotherapy, n=471; no radiotherapy, n=476). At up to 2 years, chest wall symptoms were worse in the radiotherapy group than in the no radiotherapy group (mean score 14·1 [SD 15·8] in the radiotherapy group vs 11·6 [14·6] in the no radiotherapy group; effect estimate 2·17, 95% CI 0·40-3·94; p=0·016); however, there was an improvement in both groups between years 1 and 2 (visit effect -1·34, 95% CI -2·36 to -0·31; p=0·010). No differences were seen between treatment groups in arm and shoulder symptoms, body image, fatigue, overall QOL, physical function, or anxiety or depression scores.Interpretation Postmastectomy radiotherapy led to more local (chest wall) symptoms up to 2 years postrandomisation compared with no radiotherapy, but the difference between groups was small. These data will inform shared decision making while we await survival (trial primary endpoint) results.

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