Hypofractionated radiotherapy is safe and effective for early breast cancer treatment at 10-years of follow-up

Appropriately dosed, hypofractionated radiotherapy does not harm healthy tissues and is effective in controlling locoregional early breast cancer, according to 10-year follow-up results from the U.K. Standardization of Breast Radiotherapy Trials (START), presented during the 2012 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS).

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 over 5 weeks, however several randomised trials indicate that a lower total dose delivered in fewer, larger fractions (Fr) is likely to be at least as safe and effective. However, with patients remaining at risk of local relapse for many years, information on long-term outcomes is needed to provide confidence in clinical practice.

Between 1999 and 2002 a total of 4,451 women with completely excised invasive breast cancer were recruited to either the START A or the START B trial. In START A, researchers compared 50 Gy of postsurgery radiotherapy given in 25 fractions for five weeks with 41.6 Gy or 39 Gy in 13 fractions for five weeks. In START B, 50 Gy in 25 fractions for five weeks was compared with 40 Gy in 15 fractions for three weeks.

Data revealed 139 locoregional tumor relapses among the 2,236 women in START A who were followed for an average of 9.3 years and 95 locoregional relapses in the 2,215 women in START B, followed for an average of 9.9 years. The 10-year locoregional relapse rates for START A were 7.4% after 50 Gy, 6.3% after 41.6 Gy and 8.8% after 39 Gy. In previously published data from START B, the 10-year locoregional relapse rate was 5.5% after 50 Gy and 4.3% after 40 Gy.

As such, the long-term data from START A confirm the findings of earlier studies indicating that breast cancer is as sensitive to the radiation dose of each fraction as the dose-limiting normal tissues of the breast area and this effect persists for at least 10 years. Nevertheless, a five-week, 13-fraction schedule does not offer shortened overall treatment times. Hence, the START B trial was designed, a pragmatic comparison of a three-week with a standard five-week schedule, testing for non-inferiority. START B showed that the 15-fraction schedule is definitely gentler on the healthy tissues, and the presented long-term data confirm earlier findings that it appears non-inferior in terms of tumor control.

In summary, long-term follow-up of START A and START B confirms that a lower total dose of radiation in fewer, slightly larger fractions delivered over a shorter treatment time is at least as safe and effective as standard five-week schedules of curative radiotherapy in women with early breast cancer.

Reference

J. Haviland, R. Agrawal, E. Aird et al. The UK START (Standardisation of Breast Radiotherapy) Trials: 10-year follow. Presented at SABCS 2012; Abstract S4-1.