Patient- and clinician-reported outcomes in the phase III FAST-Forward trial nodal sub-study

Published in 2020, the FAST-Forward trial established 26 Gy in five daily fractions (Fr) as standard of care for breast or chest wall adjuvant therapy for early breast cancer. The recently published FAST‑Forward nodal sub‑study investigated whether a 1-week radiotherapy schedule to axillary levels I to IV delivers similar patient-reported outcomes to the standard 3‑week regimen for people with invasive breast cancer requiring irradiation of axillary/supraclavicular nodes after surgery. Across 50 UK centres, the study randomized 469 patients to 40 Gy/15 Fr (control), 26 Gy/5 Fr, or 27 Gy/5 Fr (the 27‑Gy arm closed early).

The primary endpoint was patient‑reported moderate/marked arm or hand swelling at 5 years on the EORTC QLQ‑BR23 questionnaire, a proxy for arm lymphoedema. Among patients returning 5‑year questionnaires, moderate/marked swelling was reported by 10% (11/107) after 40 Gy/15 Fr and 11% (13/116) after 26 Gy/5 Fr - an absolute difference of 1%, meeting the pre‑specified non‑inferiority criterion, although the underpowered 27 Gy/5‑Fr group showed higher 5‑year patient‑reported arm swelling (19%). Time-to-event analyses likewise found no evidence that 26 Gy/5 Fr increased side-effects, and other patient‑reported arm/shoulder symptoms at 5 years were similar between the two arms. About 20% of patients in both arms reported mild (‘a little’) arm swelling. Clinician assessments aligned, showing comparable rates of arm lymphoedema and breast/chest wall effects.

The results suggest that the 1-week radiotherapy schedule could safely be extended to patients requiring axillary radiotherapy without irradiation of the internal mammary nodes. Pending publication of the 10-year efficacy data, and assuming similarly low recurrence rates as in the FAST-Forward main trial, in future 26 Gy /5 Fr could be offered to patients requiring adjuvant axillary radiotherapy along with the breast or chest wall. The study also provides data on the incidence of long-term arm swelling from radiotherapy, which can be used to inform patients of their risk of side-effects in the present era of axillary surgery de-escalation.

Summary Author: Mr Tim Rattay, Associate Professor in Breast Surgery and Honorary Consultant Breast Surgeon, University Hospitals of Leicester.