Shorter hypofractionated radiotherapy regimen safe, effective in early-stage breast cancer
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Adjuvant radiotherapy delivered in five fractions over 1 week appeared to be as effective as the standard 15-fraction, 3-week regimen following primary surgery for early-stage breast cancer, according to results of the randomized phase 3 FAST-Forward study published in The Lancet.
A 1-week schedule also appeared as safe as the longer regimen in terms of normal tissue effects up to 5 years, according to researchers.
“FAST-Forward was informed by the FAST trial that tested two dose levels of five once-weekly fractions,” Adrian Murray Brunt, MBBS, FRCR, professor and lead researcher at Clinical Research Network West Midlands in the United Kingdom, and colleagues wrote. “FAST trial results to 10-year follow-up are to be published soon. The trial design used dose levels estimated to be the upper and lower bounds that are isoeffective with the control schedule in terms of tumor control and normal tissue effects.”
The standard adjuvant radiotherapy schedule for patients with early-stage breast cancer was 25 fractions of 2 Gy delivered over 5 weeks until randomized trials confirmed the safety and efficacy of fewer, larger fractions for a lower total dose. Now, an international standard, adopted in the U.K. in 2009, is 15 fractions of 2.7 Gy over 3 weeks, for a total of 42.5 Gy.
Researchers in the FAST-Forward trial sought to determine whether an even shorter schedule of five once-weekly fractions would be noninferior to the standard 3-week regimen.
They randomly assigned 4,096 adults with invasive carcinoma of the breast following mastectomy or breast conservation surgery to a radiotherapy schedule of 40 Gy in 15 fractions over 3 weeks (n = 1,361; median age, 60 years), 27 Gy in five fractions over 1 week (n = 1,367; median age, 61 years) or 26 Gy in 5 fractions over 1 week (n = 1,368; median age, 61 years) to the whole breast or chest wall.
Ipsilateral breast tumor relapse served as the primary endpoint. Researchers assumed a 2% 5-year incidence for 40 Gy, and noninferiority was predefined as 1.6% or less excess for five-fraction schedules.
Median follow-up was 71.5 months (interquartile range, 71.3-71.7).
Results showed ipsilateral breast tumor relapse occurred in 31 patients in the 40 Gy group compared with 27 patients in the 27 Gy group (HR = 0.86; 95% CI, 0.51-1.44) and 21 patients in the 26 Gy group (HR = 0.67; 95% CI, 0.38-1.16).
Researchers observed 5-year incidence of ipsilateral breast tumor relapse of 2.1% (range, 1.4-3.1) after 40 Gy. Estimated absolute differences in cumulative incidence vs. 40 Gy in 15 fractions were 0.3% (95% CI, 1 to 0.9) for 27 Gy in five fractions and 0.7% (95% CI, 1.3 to 0.3) for 26 Gy in five fractions.
Moderate or marked clinician-assessed normal tissue effects in the breast or chest wall at 5 years occurred in 98 (9.9%) of 986 patients in the 40 Gy group, 155 (15.4%) of 1,005 patients in the 27 Gy group, and 121 (11.9%) of 1,020 patients in the 26 Gy group.
Across clinician assessments from 1 year to 5 years, results showed significantly higher risk for any moderate or marked effect in the chest or breast wall in the 27 Gy group (OR = 1.55; 95% CI, 1.32-1.83), but no significant difference in the 26 Gy group (OR = 1.12; 95% CI, 0.94-1.34), compared with the 40 Gy group.
Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy vs. 40 Gy, but not for 26 Gy vs. 40 Gy.
The small sample size served as a limitation to this study.
“The consistency of FAST-Forward results with earlier hypofractionation trials supports the adoption of 26 Gy in five daily fractions as a new standard for women with operable breast cancer requiring adjuvant radiotherapy to partial or whole breast,” Brunt and colleagues wrote. – by John DeRosier
Disclosures: Brunt reports research funding from Cancer Research UK, Health Technology Assessment and National Institute for Health Research during the conduct of the study, as well as research funding from AstraZeneca, Clovis Oncology, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Puma Biotechnology, Pfizer and Roche outside this study. Please see the study for all other authors’ relevant financial disclosures.
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