Abstract
PURPOSEPrevious 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.METHODSWomen ≥ 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 once-weekly fr of 6.0 or 5.7 Gy. 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.RESULTSA 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.CONCLUSIONAt 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.
Highlights
At 10 years, there was no significant difference in normal tissue effects (NTE) rates after 28.5 Gy Schedulea (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 onceweekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen
Fifteen- or 16-fraction regimens are unlikely to represent the clinical limits of hypofractionation, and 3-year adverse effects of 5-fraction schedules in the UK FAST trial were reported in 2011.9 In FAST, 5.7 or 6.0 Gy once weekly were tested against 50 Gy in 25 fractions, the standard of care at the time
Summary
Ten-year results of 4 randomized trials totaling . 7,000 patients confirm the safety and efficacy of hypofractionated radiotherapy after primary surgery for early breast cancer.[1,2,3,4] The UK START-B and Ontario trials established 15- and 16-fraction schedules as new standards of care delivered over 21-22 days.[5,6,7] Sensitivity to fraction size was tested in the START pilot and START-A trials by controlling for treatment time, generating an a/b estimate of 3.5 Gy (95% CI, 1.2 to 5.7) for tumor control, comparable to that for late adverse effects.[2,4,8] Fifteen- or 16-fraction regimens are unlikely to represent the clinical limits of hypofractionation, and 3-year adverse effects of 5-fraction schedules in the UK FAST trial were reported in 2011.9 In FAST, 5.7 or 6.0 Gy once weekly were tested against 50 Gy in 25 fractions, the standard of care at the time. The explanatory trial design allowed interpolation between 2 5-fraction schedules that suggested a schedule equivalent to 50 Gy in 25 fractions in terms of late adverse effects. Five fractions of 5.7 and 6.0 Gy were predicted to be radiobiologically equivalent to 25 fractions of 2.0 Gy, assuming a/b values of 3.0 and 4.0 Gy for late normal tissue responses and tumor control, respectively.[10] At a median follow-up of 3 years, 28.5 Gy in 5 fractions was comparable to 50 Gy in 25 fractions and milder than 30 Gy in 5 fractions in terms of adverse effects in the breast.[9] This manuscript presents the 5-year results for change in photographic breast appearance and physician assessments of breast normal tissue effects (NTE) up to 10 years after radiotherapy, as well as breast cancer disease events
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