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

The whole breast clinical target volume, including the soft tissues from 5 mm below the skin surface to the deep fascia, was either established from field-based tangential fields or the volume was contoured prospectively. Post-mastectomy chest wall clinical target volume encompassed post-surgical skin flaps and underlying soft tissues to the deep fascia; both excluded underlying muscle and rib cage. Surgeons were strongly encouraged to mark the tumour cavity walls with titanium clips or gold seeds at the time of breast conservation surgery in order to aid placement of tangential fields and delineation of tumour bed. A typical margin of 10 mm was added around the breast or chest wall clinical target volume accounting for set-up error, breast swelling, and breathing to create a planning target volume (PTV). For all patients, a full 3D CT set of outlines covering the whole breast and organs at risk was collected with a slice separation up to 5 mm, and organs at risk were outlined prospectively. A tangential opposing pair beam arrangement encompassed the whole breast or chest wall PTV, minimising the ipsilateral lung and heart exposure. The treatment plan was optimised with 3D dose compensation to achieve the following PTV dose distribution: more than 95% of PTV received 95% of prescribed dose, less than 5% of PTV received 105% or more, less than 2% of PTV received 107% or more, and a global maximum of less than 110%. Dose constraints for the control group were as follows: volume of ipsilateral lung receiving 12 Gy less than 15%, and volume of heart receiving 2 Gy less than 30% and that receiving 10 Gy less than 5%. Dose constraints for the five-fraction schedules were as follows: volume of ipsilateral lung receiving 8 Gy less than 15%, and volume of heart receiving 1·5 Gy less than 30% and that receiving 7 Gy less than 5%. X-ray beam energies for treatment were 6 MV or 10 MV, but a mixture of energies—eg, 6 MV and 10–15 MV—was allowed for larger patients, assessed on a case-by-case basis. Tumour bed boost was delivered via electrons or photons. Verification was done using electronic portal imaging using MV or kV x-rays. Control group treatment verification was required for at least three fractions in the first week with correction for any systematic error and then once weekly with a tolerance of 5 mm. The five-fraction schedules required verification imaging for each fraction with recommendations to correct all measured displacements. A comprehensive quality assurance programme involved every radiotherapy centre before trial activation and continued throughout trial accrual; this was coordinated by the UK Radiotherapy Trials Quality Assurance team based at Mount Vernon Hospital, Northwood, UK. The radiotherapy planning pack is in the appendix (pp 79–103).

Patients were assessed by clinicians for ipsilateral breast tumour relapse and late normal tissue effects at annual follow-up visits. Starting 12 months after trial entry, late-onset normal tissue effects in ipsilateral breast or chest wall (breast distortion, shrinkage, induration and telangiectasia; and breast or chest wall oedema and discomfort) were graded by clinicians on a four-point scale (none, a little, quite a bit, or very much), interpreted as none, mild, moderate, or marked. Symptomatic rib fracture, symptomatic lung fibrosis, and ischaemic heart disease were recorded. Clinical assessments of acute skin toxicity have been previously reported.