Patient- and clinician-assessed five-year normal tissue effects following one-week versus three-week axillary radiotherapy for breast cancer: Results from the phase III FAST-Forward trial randomised nodal sub-study

BACKGROUND AND PURPOSE: FAST-Forward showed that 26 Gray (Gy) in 5 fractions (Fr) over one week adjuvant radiotherapy to breast or chest wall was as safe and effective as a three-week schedule (40 Gy/15Fr) for early breast cancer. The nodal sub-study investigated whether a one-week schedule is safe for adjuvant axillary radiotherapy. MATERIALS AND METHODS: In this randomised, non-inferiority, non-blinded sub-study (ISRCTN19906132), patients with invasive breast cancer (pT1-3, pN1-3a, M0) following surgery requiring axillary radiotherapy (any or all levels 1-4) were randomised to 40 Gy/15Fr (three weeks, control), 26 Gy/5Fr or 27 Gy/5Fr (one week) atlas-based radiotherapy planning, including quality assurance. The 27 Gy/5Fr group closed early due to three-year main trial normal tissue effects suggesting 26 Gy/5Fr would be optimal; this analysis focusses on comparison between 26 Gy/5Fr and control. Primary endpoint was five-year patient-reported moderate or marked arm or hand swelling, aiming to exclude a 10 % increase (assuming 10 % incidence with control; 90 % power, one-sided α = 0.05, n = 172 per group). RESULTS: 469 patients were randomised from 50 UK centres (182 40 Gy/15Fr, 183 26 Gy/5Fr, 104 27 Gy/5Fr). Median age 61 years; 250 (54 %) and 182 (39 %) had grade 2 and 3 tumours respectively; 261 (56 %) had axillary dissection. Of those who completed a five-year questionnaire, 11/107 (10 %) 40 Gy/15Fr and 13/116 (11 %) 26 Gy/5Fr reported moderate or marked arm or hand swelling, difference 1 % (90 % confidence interval -6%, 8 %, p = 0.49). Other arm and shoulder symptoms were similar between groups with no cases of brachial plexopathy. CONCLUSION: Five-year patient-reported normal tissue effects suggest 26 Gy/5Fr/1-week hypofractionation is safe for breast cancer patients requiring adjuvant axillary radiotherapy.