Abstract
IntroductionThe phase 3 FAST-Forward trial reported outcomes for 26 and 27 Gy schedules delivered in 5 fractions over 1 week versus 40 Gy in 15 fractions over 3 weeks in 4000 patients. We discuss concerns raised by the radiotherapy community in relation to implementing this schedule. Ipsilateral Breast Tumour Relapse (IBTR)Published estimated 5-year IBTR with 95% CI after 40 Gy in 15 fractions was 2.1% (95% CI 1.4–3.1), 1.7% (1.2–1.6) after 27 Gy and 1.4% (0.2–2.2) after 26 Gy, emphatically showing non-inferiority of the 5-fraction regimens. Subgroup analyses comparing IBTR in 26 Gy versus 40 Gy show no evidence of differential effect regarding age, grade, pathological tumour size, nodal status, tumour bed boost, adjuvant chemotherapy, HER2 status and triple negative status. The number of events in these analyses is small and results should be interpreted with caution. There was only 1 IBTR event post-mastectomy. Normal tissue effectsThe 26 Gy schedule, on the basis of similar NTE to 40 Gy in 15 fractions, is the recommended regimen for clinical implementation. There is a low absolute rate of moderate/marked NTE, these are predominantly moderate not severe change. Subgroup analyses comparing clinician-assessed moderate or marked adverse effect for 26 Gy versus 40 Gy show no evidence of differential effects according to age, breast size, surgical deficit, tumour bed boost, or adjuvant chemotherapy. Radiobiological considerationsThe design of the FAST-Forward trial does not control for time-related effects, and the ability to interpret clinical outcomes in terms of underlying biology is limited. There could conceivably be a time-effect for tumour control. A slight reduction in α/β estimate for the late normal tissue effects of test regimens might be a chance effect, but if real could reflect fewer consequential late effects due to lower rates of moist desquamation. ConclusionThe 26 Gy 5-fraction daily regimen for breast radiotherapy can be implemented now.
Highlights
The phase 3 FAST-Forward trial reported outcomes for 26 and 27 Gy schedules delivered in 5 fractions over 1 week versus 40 Gy in 15 fractions over 3 weeks in 4000 patients
In FAST-Forward, retrospective subgroup analyses comparing the time to first clinician-assessed moderate or marked adverse effect in the breast or chest wall for 26 Gy versus 40 Gy provided no evidence of a differential effect of the five-fraction schedule according to age, breast size, surgical deficit, tumour bed boost or adjuvant chemotherapy, as confidence intervals for subgroups overlapped, the power for these retrospective subgroup analyses was low (Figure 2)
We conclude that 26 Gy in five daily fractions for breast radiotherapy is an effective regimen for tumour control
Summary
The phase 3 FAST-Forward trial reported outcomes for 26 and 27 Gy schedules delivered in 5 fractions over 1 week versus 40 Gy in 15 fractions over 3 weeks in 4000 patients. The phase III randomised FAST-Forward trial [4] reported outcomes, in relation to both tumour control and normal tissue effects (NTE), for 26 and 27 Gy in five fractions over 1 week versus 40 Gy in 15 fractions over 3 weeks in more than 4000 patients.
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