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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a b s t r a c tBackground and Purpose: Large breast size is associated with an increased risk of late adverse effects after breast conservation surgery and radiotherapy, even when 3D dosimetry is used. The purpose of this study is to test the hypothesis that residual dose inhomogeneity is sufficient to explain the association. Methods: Patients previously treated after breast conservation surgery with whole breast radiotherapy using 3D dosimetry and followed up in the UK FAST hypofractionation trial were selected for this analysis. The residual level of dose inhomogeneity across the whole breast treatment volume was used to test for association between residual dosimetry and post-treatment change in breast appearance at 2 years post-radiotherapy. Results: At 2 years, 201/279 (72%) of women had no change in photographic breast appearance, 61 (22%) had mild change and 17 (6%) had marked change. Breast size and dosimetry were both significantly associated with late effects in univariate analyses, but only breast size remained an independent significant risk factor for change in breast appearance when included in a multiple regression model together with other prognostic factors (p = 0.006 for trend). Conclusion: Large-breasted women are more likely to suffer change in breast size and shape after whole breast radiotherapy delivered using 3D dosimetry, but residual dose inhomogeneity is insufficient to explain the association.Ó 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2011) xxx-xxxThere is retrospective evidence that breast size is a risk factor for late adverse effects following breast conservation surgery and adjuvant radiotherapy for early breast cancer [1][2][3][4][5][6][7][8][9]. Body mass index, correlated to breast size and brassiere size, has also been linked to the risk of acute skin reactions and to late cosmesis [10][11][12]. Not all studies are confirmatory, but the weight of evidence suggests that the association between the size of the breast and the risk of early and late adverse effects in the breast is real [13][14][15][16]. Analyses are based on assessments of late adverse effects made in clinic or from photographs, focusing on changes in breast size and shape, breast oedema and telangiectasia. Marked acute skin reactions in the inframammary fold of heavy-breasted patients may explain part of the association via an increased risk of consequential late effects.Suboptimal dosimetry is thought to explain at least part of the association between breast size and risk of late normal tissue damage after radiotherapy delivered using 2D techniques [1,2,4,6,17]. A cause and effect relationship is supported by the 5-year results of a randomised trial (N = 306) comparing 2D and 3D radiation dosimetry [18], but not so far by the 2-year results of a larger confirmatory study [19]. Assuming dose distribution matters, it is not known if residual dose inhomogeneity in patients treated using 3D dosimetry explains a significant component of late adverse effects in large breasted w...

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