Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial
- Study type
- Clinical trial
- Study name
- FAST-Forward
- Phase
- Phase 3
- Design
- Multicentre, randomised, non-inferiority trial (allocation not masked because of the nature of the intervention)
- Sample size
- 4096 patients
- Source
- The Lancet · 2020
In plain words
In this large study, radiotherapy after surgery for early breast cancer given over 3 weeks (15 sessions) was compared with two shorter 1-week schedules (5 sessions). After about 5 years, the 1-week schedule with a dose of 26 Gy was no less effective than the 3-week schedule at preventing the cancer coming back in the breast, and side effects on the healthy breast tissue were also similar. The 27 Gy schedule caused more side effects in healthy tissue. You should make the final decision about the type of radiotherapy with your doctor.
Key results
Treatment arms and regimens
40 Gy in 15 fractions (2.67 Gy per fraction) over 3 weeks to the whole breast or chest wall (1361 patients). A sequential tumour bed boost in the conserved breast was allowed (10 or 16 Gy in 2 Gy fractions; boost intent and dose were decided before randomisation). Nodal radiotherapy was not allowed in the main study; concurrent endocrine therapy or trastuzumab was allowed, but concurrent chemotherapy was not.
27 Gy in 5 fractions (5.4 Gy per fraction) over 1 week to the whole breast or chest wall (1367 patients). A sequential tumour bed boost in the conserved breast was allowed (10 or 16 Gy in 2 Gy fractions; boost intent and dose were decided before randomisation). Nodal radiotherapy was not allowed in the main study; concurrent endocrine therapy or trastuzumab was allowed, but concurrent chemotherapy was not.
26 Gy in 5 fractions (5.2 Gy per fraction) over 1 week to the whole breast or chest wall (1368 patients). A sequential tumour bed boost in the conserved breast was allowed (10 or 16 Gy in 2 Gy fractions; boost intent and dose were decided before randomisation). Nodal radiotherapy was not allowed in the main study; concurrent endocrine therapy or trastuzumab was allowed, but concurrent chemotherapy was not.
Source of the regimen details: Full text of the paper (PMC7262592, Participants and Randomisation and masking sections)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients aged ≥18 years (women or men) with invasive breast carcinoma (pT1-3, pN0-1, M0) after microscopically complete excision of the tumour by breast-conserving surgery or mastectomy (reconstruction allowed), at 97 hospitals in the UK (47 radiotherapy centres and 50 referring hospitals). All patients had axillary surgery (sentinel node biopsy or axillary clearance). A protocol amendment on 15 February 2013 excluded the lowest-risk patients (65 years and older, pT1, grade 1 or 2, ER-positive, HER2-negative, pN0, M0).
Endpoints
Primary endpoint: ipsilateral breast tumour relapse. Assuming a 5-year incidence of 2% with 40 Gy, non-inferiority was predefined as an increase of ≤1.6% for the five-fraction regimens (critical hazard ratio 1.81). Normal tissue effects were assessed by clinicians, by patients and from photographs.
Safety and side effects
At 5 years, moderate or marked clinician-assessed normal tissue effects in the breast or chest wall were reported in 9.9% of the 40 Gy group, 15.4% of the 27 Gy group and 11.9% of the 26 Gy group. Across all clinical assessments from year 1 to 5, the odds ratio versus 40 Gy was 1.55 (95% CI 1.32 to 1.83; P<0.0001) for 27 Gy and 1.12 (0.94 to 1.34; P=0.20) for 26 Gy. Patient and photographic assessments also showed a higher risk of normal tissue effects for 27 Gy versus 40 Gy, but not for 26 Gy versus 40 Gy.
Clinical significance and place in guidelines
According to the abstract, 26 Gy in 5 fractions over 1 week is non-inferior to 40 Gy in 15 fractions for local control and has similar normal tissue safety up to 5 years; this regimen can be a shorter option for adjuvant breast radiotherapy. The 27 Gy dose was associated with more normal tissue effects. Its adoption in clinical guidelines should be checked separately.
Limitations
Treatment allocation was not masked because of the nature of the intervention. The results of this report cover up to 5 years of follow-up, and longer-term late effects are not examined in this abstract. The study population was UK patients with early breast cancer (pT1-3, pN0-1).
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.