FAST-Forward 10-year outcomes support 26 Gy as international standard for 1-week breast radiotherapy.

Evidence before this study

In the context of radiotherapy after primary surgery for breast cancer, to the best of our knowledge, there have been four large, randomised, phase 3 clinical trials with 10-year follow-up (totalling 7000 participants across the four trials) that have shown that delivering radiotherapy daily over 3 weeks (in 15 or 16 daily treatments or fractions) is as effective at reducing risk of recurrence as the traditional 5-week schedules (25 fractions). In 2008, Bentzen and colleagues showed that a schedule of 40 Gy in 15 fractions over 3 weeks reduced adverse effects on normal tissues than a schedule of 50 Gy in 25 fractions over 5 weeks and became an international standard of care from 2009. Outcomes from a five-fraction schedule delivered over 5 weeks (FAST trial) suggested further scope for reducing the burden of curative radiotherapy for people with early breast cancer. Evidence to inform the FAST-Forward trial design was based on a PubMed search done in 2009 using the search terms breast cancer, radiotherapy, fractionation, and trials, as well as direct communication with international researchers; no formal meta-analysis was done. The trial was designed to compare two 1-week schedules (26 Gy in five fractions over 1 week and 27 Gy in five fractions over 1 week) against the standard of care 40 Gy in 15 fractions over 3 weeks schedule for adjuvant radiotherapy to the breast or chest wall after primary breast surgery (breast conservation or mastectomy).

Added value of this study

The 10-year outcomes from the FAST-Forward trial support that both 1-week schedules (26 Gy in five fractions over 1 week and 27 Gy in five fractions over 1 week) are as effective as a 40 Gy in 15 fractions over 3 weeks schedule in terms of 10-year cumulative incidence of ipsilateral breast recurrence. At 10 years, incidence of moderate or marked patient-reported and clinician-reported breast or chest wall side-effects were similar for the 40 Gy in 15 fractions and 26 Gy in five fractions. As seen in the primary analysis, incidences of these effects were slightly higher with 27 Gy in five fractions over 1 week, suggesting this schedule is suboptimal. Although not powered for efficacy outcomes, 5-year data from the nodal substudy reported here show that, for those receiving axillary radiotherapy, incidence of locoregional recurrence was low with both 26 Gy in five fractions over 1 week and 40 Gy in 15 fractions over 3 weeks schedules, consistent with main trial results.

Implications of all the available evidence

The 10-year outcomes from FAST-Forward support a 26 Gy in five fractions over 1 week schedule as the international standard of care for adjuvant radiotherapy to the breast or chest wall in early breast cancer. 5-year results from the axillary nodal substudy show the 26 Gy schedule is safe and efficacy data are reassuringly consistent with the main trial. However, sample size limits the precision of efficacy estimates for this subgroup on its own. This uncertainty should be part of shared decision making for those patients considering 26 Gy axillary radiotherapy. Shorter radiotherapy schedules reduce the burden of breast cancer treatment on patients, health services, and the environment.

Source: The Lancet Oncology