FAST-Forward

Design, population and eligibility

Treatment and comparator

40 Gy in 15 fractions over 3 weeks versus 27 Gy in 5 daily fractions over 1 week versus 26 Gy in 5 daily fractions over 1 week. The 26 Gy schedule is the key clinically adopted regimen.

Primary and secondary endpoints

Primary endpoint: ipsilateral breast tumour recurrence at 5 years with a prespecified non-inferiority margin. Ten-year update reports cumulative ipsilateral breast recurrence and late normal-tissue effects; axillary substudy reports 5-year efficacy.

Key efficacy results

At median follow-up 10.1 years, 10-year cumulative ipsilateral breast recurrence was 3.6% (95% CI 2.7–4.9) with 40 Gy, 2.9% (2.1–4.0) with 27 Gy, and 2.1% (1.5–3.1) with 26 Gy. The original 5-year primary analysis established non-inferiority of 26 Gy and 27 Gy to 40 Gy. The numerical 10-year differences do not establish superiority.

Ten-year clinician-reported moderate/marked breast or chest-wall effects: 13.1% with 40 Gy, 19.3% with 27 Gy and 14.4% with 26 Gy.

Source-reported outcome visualization

Ten-year ipsilateral breast recurrence and moderate/marked late effects.

The 5-fraction schedules met the original non-inferiority objective at 5 years. The 10-year numerical recurrence differences are descriptive; no superiority claim is made.

Absolute effect

At 10 years, the observed cumulative recurrence was 2.1% with 26 Gy/5 versus 3.6% with 40 Gy/15 (descriptive difference 1.5 percentage points). Because this is a non-inferiority trial and the 10-year update is not a superiority test, no NNT for recurrence prevention is assigned. Ten-year moderate/marked late effects were 14.4% with 26 Gy and 13.1% with 40 Gy.

Trial-specific toxicity and treatment burden

Ten-year clinician-reported moderate/marked breast or chest-wall effects: 13.1% (40 Gy), 19.3% (27 Gy) and 14.4% (26 Gy). The 26 Gy schedule showed late effects similar to the 3-week schedule; 27 Gy had a higher rate. These are clinician-reported late effects, not grade 3–5 toxicity rates. Five-fraction treatment reduces attendance from 15 to 5 fractions.

Quality of life and patient-reported outcomes

The main publication emphasizes clinician-reported normal-tissue effects; do not infer a QoL benefit from fewer visits alone. Reduced travel and treatment burden are clear logistical advantages, but patient-reported outcomes should be cited from the relevant dedicated analyses if quantified.

Subgroups and applicability

The 10-year main trial supports breast/chest-wall treatment. The axillary substudy enrolled 469 (466 ITT), with median follow-up 7.0 years and 32 locoregional recurrences; its sample size limits precision for nodal irradiation independently.

Current-practice context · reviewed 3 November 2026

26 Gy in 5 fractions over 1 week is supported as a standard adjuvant breast/chest-wall schedule for appropriate patients. Care is required when applying the regimen to comprehensive regional nodal irradiation; the substudy is reassuring but smaller.

Limitations and critical interpretation

The main trial was designed for non-inferiority, not superiority. The 27 Gy arm had higher late effects. The axillary cohort is smaller and ongoing follow-up is needed. Do not infer 10-year superiority from numerically lower recurrence in the 26 Gy arm.

Bottom line: FAST-Forward provides mature 10-year evidence supporting 26 Gy in five fractions for adjuvant breast/chest-wall RT, with major treatment-burden reduction. Nodal application requires attention to the smaller substudy evidence base.

Primary sources and follow-up publications

1. 10-year report, Lancet Oncology 2026
2. Primary 5-year report, Lancet 2020
3. Trial registry

Outcome values are sourced from the linked reports. Unreported values are not imputed. NNT/NNH is only stated when an explicit fixed-time absolute difference supports a defensible calculation; no NNT is derived from median survival.