The international standard radiotherapy schedule for early breast cancer delivers 50 Gy of radiation in 25 fractions of 2.0 Gy over 5 weeks. However, cancer specialists in the United Kingdom believe that a lower total dose delivered in fewer, larger fractions can be at least as safe and effective as this standard schedule. Professor John Yarnold, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK; Professor Judith Bliss, Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK; and colleagues from the START trials collaborative group, comprising researchers from 35 UK cancer centres, carried out both START trials to test this hypothesis. Their conclusions come after 10 years of work on these trials. The studies were jointly funded by Cancer Research UK, the UK Medical Research Council, and the UK Department of Health.

START A included 2,236 women with early breast cancer from 17 centres in the United Kingdom. After primary surgery, the women were randomly assigned to receive 50 Gy in 25 fractions of 2.0 Gy (n = 749) versus 41.6 Gy in 13 fractions of 3.2 Gy (n = 750) or 39 Gy in 13 fractions of 3.0 Gy (n = 737). All regimens were given over 5 weeks, and women were eligible if they were aged over 18 years, did not have immediate surgical reconstruction, and were available for follow-up. The endpoints of the trial were tumour relapse, defined as the reappearance of cancer at irradiated sites; the effect of the regimen on normal or "cancer-free" tissues; and quality of life for the patient.

The researchers found that after a median follow-up of 5.1 years, the rate of tumour relapse at 5 years was 3.6% after 50 Gy, 3.5% after 41.6 Gy, and 5.2% after 39 Gy. Neither late adverse effects nor local tumour relapse after 41.6 Gy were different compared with 50 Gy, ie, the absolute difference in local tumour relapse could be up to 1.3% better and at most 2.6% worse after 41.6 Gy. Both photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy. The authors concluded that "a lower total dose (41.6 Gy) in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions."

START B included 2,215 women with early breast cancer from 23 centres in the UK. After primary surgery, they were randomly assigned to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks (n = 1,105) and 40 Gy in 15 fractions of 2.67 Gy over 3 weeks (n = 1,110). The eligibility for the trial and its measured endpoints were the same as for Start A.

The researchers found that after a median follow-up of 6.0 years, the rate of tumour relapse at 5 years was 2.2% in the 40-Gy group and 3.3% in the 50-Gy group, which translated into an absolute difference of between -1.7% and +0.9% in the 40-Gy group, ie, the absolute difference in tumour relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Again, both photographic and patient self-assessments suggested lower rates of late adverse effects after 40 Gy compared with 50 Gy.

The authors concluded that "after surgery for early breast cancer, a radiotherapy schedule delivering 40 Gy in 15 fractions over 3 weeks seems to offer local regional tumour control and rates of late normal tissue effects at least as good as the accepted international standard of 50 Gy in 25 fractions over 5 weeks."

In an accompanying Comment, Harry Bartelink, MD, Netherlands Cancer Institute, Amsterdam, Netherlands, and Rodrigo Arriagada, MD, Institut Gustave Roussy, Villejuif, France, said, "We realise that hypofractionation is convenient for patients, because it reduces the number of visits to radiotherapy departments and waiting lists in several cancer centres. Nevertheless we have to wait for data on longer follow-up before final conclusions can be drawn from the START trials."


SOURCE: The Lancet

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