KEY POINTS
- The review evaluates ultrahypofractionated breast RT across accelerated partial-breast irradiation, whole-breast irradiation, regional nodal irradiation, and postmastectomy RT, with particular emphasis on regimens delivering approximately five fractions.
- For external-beam APBI, 30 Gy in 5 fractions is favored over twice-daily 38.5 Gy in 10 fractions. In the Florence randomized trial, 10-year ipsilateral breast recurrence was 3.7% with APBI versus 2.5% with WBI (HR 1.56, 90% CI 0.55–4.37), with significantly less grade ≥2 acute and late toxicity after APBI.
- For whole-breast irradiation, FAST and FAST-Forward established that five-fraction schedules can preserve tumor control in appropriately selected early breast cancer patients, supporting routine use of 26 Gy in 5 fractions over one week in contemporary practice.
- The FAST-Forward nodal substudy provides the strongest randomized RNI evidence: among 469 patients, moderate/marked arm or hand swelling at five years was 11% with 26 Gy/5 fractions versus 10% with 40 Gy/15 fractions.
- In the nodal substudy, five-year ipsilateral breast recurrence was 1.2% versus 1.8% and locoregional recurrence 4.2% versus 4.1% with 26 Gy and 40 Gy, respectively. However, the substudy was not powered for efficacy endpoints.
- Evidence becomes thinner when internal mammary nodes, postmastectomy treatment, reconstruction, or more complex systemic-therapy scenarios are included. The review specifically cautions that long-term cardiac data after ultrahypofractionated IMN irradiation remain insufficient.
- Intraoperative RT is treated separately from modern external-beam APBI; long-term randomized evidence, particularly from ELIOT, shows substantially higher local recurrence than standard external-beam WBI and does not support considering these approaches interchangeable.
CLINICAL TAKEAWAY
Five-fraction RT has moved from experimental to routine treatment for selected whole-breast and partial-breast indications. Extending the same confidence to comprehensive RNI or PMRT is less straightforward, especially when internal mammary nodes or reconstruction are involved, because mature toxicity and efficacy data remain limited.