The UK START (Standardisation of Breast Radiotherapy) Trials; 10-year follow-up results. On behalf of the START Trialists

Haviland, J.S., Agrawal, R., Aird, E., Barrett, J., Barrett-Lee, P., Brown, J., Dewar, J., Dobbs, J., Hopwood, P., Hoskin, P., Lawton, P., Magee, B., Mills, J., Morgan, D., Owen, R., Simmons, S., Sydenham, M., Veneables, K., Bliss, J. and Yarnold, J. (2012) The UK START (Standardisation of Breast Radiotherapy) Trials; 10-year follow-up results. On behalf of the START Trialists. Cancer Research, 72 (24), supplement 3. (doi:10.1158/0008-5472.SABCS12-S4-1).

Abstract

Background: international standard adjuvant radiotherapy regimens following primary surgery for early breast cancer have historically delivered a high total dose (50Gy) in 25 small daily doses (fractions) over 5 weeks, however randomised trials, including START, indicate that a lower total dose delivered in fewer, larger fractions (Fr) is likely to be at least as safe and effective (START Trialists' Group, Lancet 2008 & Lancet Oncol 2008). With patients remaining at risk of local relapse for many years, information on long-term outcomes is needed to provide confidence in clinical practice. Here, we report 10-year follow-up of the UK START Trials testing 13- and 15-Fr regimens in terms of local cancer control and late adverse effects.

Methods: between 1999 and 2002, 4451 women with completely excised invasive breast cancer (T1-3, N0-1, M0) were randomised after primary surgery to comparisons of 50Gy in 25Fr over 5 weeks vs 41·6Gy or 39Gy in 13Fr over 5 weeks (START A), or 50Gy in 25Fr over 5 weeks vs 40Gy in 15Fr over 3 weeks (START B). Women were eligible if aged over 18 years and did not have an immediate surgical reconstruction. Protocol-specified principal endpoints were local-regional (LR) tumour relapse and late normal tissue effects. Analysis was by intention to treat.

Findings: median follow-up in survivors is now 9.3 years in START A and 9.9 years in START B, with 139 LR relapses in START A and 95 in START B. In START A, the 10-year rate of LR relapse was 7.4% (95%CI 5.5–10.0) after 50Gy, 6.3% (95%CI 4.7–8.5) after 41·6Gy and 8.8% (95%CI 6.7–11.4) after 39Gy. In START B, the 10-year rate of LR relapse was 5.5% (95%CI 4.2–7.2) after 50Gy and 4.3% (95%CI 3.2–5.9) after 40Gy. Clinician assessments suggested lower 10-year rates of any moderate/marked late normal tissue effects after 39Gy (43.9%; 95%CI 39.3–48.7) and similar rates after 41.6Gy (49.5%; 95%CI 44.9–54.3) compared with 50Gy (50.4%; 95%CI 45.8–55.3) in START A and lower rates after 40Gy in START B (37.9%; 95%CI 34.5–41.5) compared with 50Gy (45.3%; 95%CI 41.7–49.0). From a planned meta-analysis of START A and the START pilot trial (Owen et al, Lancet Oncol 2006), the adjusted estimate of ?/? value for tumour control was 3.5Gy (95% CI 1.2–5.7) and for late change in photographic breast appearance was 3.1Gy (95% CI 2.0–4.2).

Interpretation: long-term follow-up confirms that breast cancer and the surrounding dose-limiting healthy tissues respond similarly to radiotherapy fraction size and thus that appropriately-dosed hypofractionated radiotherapy is safe and effective in treatment of patients with early breast cancer. 41·6Gy in 13Fr and 40Gy in 15Fr each appear comparable to 50Gy in 25Fr in terms of local-regional tumour control and late normal tissue effects. These results support the continued use of 40Gy in 15Fr as standard of care (UK NICE Guidance 2009) for women requiring adjuvant radiotherapy for early breast cancer

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