August 19, 2020
2 min read
Brunt reports consultant/advisory roles with Genomic Health and Roche; speakers bureau roles for Bristol-Myers Squibb, Genomic Health, Novartis and Roche; and research funding from Novartis and Roche. Please see the study for all authors’ relevant financial disclosures. Whelan reports no relevant financial disclosures.
Adjuvant whole-breast radiotherapy delivered in a five-fraction, once-weekly schedule appeared safe and effective for women with early breast cancer, according to 10-year results of the FAST trial published in Journal of Clinical Oncology.
“The FAST trial identifies a five-fraction schedule estimated to be radiobiologically equivalent to the 25-fraction standard in terms of late normal tissue effects,” Adrian Murray Brunt, FRCR, researcher in the Clinical Trials and Statistics Unit at The Institute of Cancer Research in London, and colleagues wrote. “[While] not powered for tumor control, the FAST Trial suggests that for patients at low risk for relapse and for whom daily visits over 3 to 5 weeks are not possible because of frailty or comorbidities, 28 Gy in five fractions as a once-weekly schedule may be an appropriate alternative to no treatment.”
Brunt and colleagues assessed this whole-breast radiotherapy schedule against the standard regimen of 50 Gy in 25 fractions among 915 women aged 50 years and older (mean age, 62.9 years) with lower-risk invasive breast carcinoma.
Participants in the phase 3 FAST trial were recruited from 18 centers in the U.K. between 2004 and 2007 and randomly assigned to one of three whole-breast radiotherapy schedules: 50 Gy in 25 fractions over 5 weeks, 30 Gy in five fractions over 5 weeks or 28.5 Gy in five fractions over 5 weeks.
Change in photographic breast appearance at 2 years and 5 years served as the primary endpoint. Physician assessments of normal tissue effects and local tumor control served as secondary endpoints.
Researchers obtained 5-year photographs for 71% of eligible women.
Results showed ORs for change in photographic breast appearance, compared with 50 Gy, of 1.64 (95% CI, 1.08-2.49) for 30 Gy and 1.1 (95% CI, 0.7-1.71) for 28.5 Gy.
The alpha/beta estimate for photographic endpoint was 2.7 Gy (95% CI, 1.5-3.9), and using this estimate, a five-fraction schedule of 28 Gy (95% CI, 26-30) was estimated to be isoeffective with 50 Gy/25 fractions, according to the researchers.
Compared with 50 Gy, ORs for moderate or marked physician-assessed breast normal tissue effects were 2.12 (95% CI, 1.55-2.89) for 30 Gy and 1.22 (95% CI, 0.87-1.72) for 28.5 Gy.
At median follow-up of 9.9 years (interquartile range, 8.3-10.1), researchers reported 96 deaths (30 at 50 Gy, 33 at 30 Gy and 33 at 28.5 Gy) and 11 ipsilateral breast cancer events (three at 50 Gy, four at 30 Gy and four at 28.5 Gy).
The FAST Trial was not powered for formal statistical comparison of local tumor control, the researchers noted.
“Results conrm the published 3-year ndings that a once-weekly, five-fraction schedule of whole-breast radiotherapy can be identied that appears to be radiobiologically comparable for normal tissue effects to a conventionally fractionated regimen,” the researchers wrote.
The study had a number of limitations, including being underpowered, according to an accompanying editorial by Timothy Whelan, BM, BCh, of the Juravinski Cancer Center in Canada, and colleagues. However, they noted that the results appeared promising.
“The potential benefits of hypofractionation, including patient convenience, improved quality of life and lower health care costs, are considerable,” the editorial authors wrote. “The investigators in the United Kingdom are to be commended on their excellent work in developing and evaluating more extensive hypofractionation.”