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. Keywords: Breast neoplasms; Clinical trials; Lymphatic irradiation; Patient reported outcomes; Radiotherapy; Radiotherapy dose hypofractionation.

Citation

Brunt, A. M., Cafferty, F. H., Wheatley, D., Sydenham, M. A., Kirby, A. M., Coles, C. E., Patel, J., Alhasso, A., Chan, C., Cleator, S., Fleming, H., Gahir, D., Goodman, A., Griffin, C., Haviland, J. S., Kirwan, C., Nabi, Z., Poole, K., Sawyer, E., Sinclair, J., … Bliss, J. M. (2025). 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. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 207, 110915. https://doi.org/10.1016/j.radonc.2025.110915

DOI

10.1016/j.radonc.2025.110915

URI

https://hdl.handle.net/20.500.14709/401

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CC BY 4.0

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CC BY 4.0

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https://creativecommons.org/licenses/by/4.0/