Ten-year follow-up results from the U.K. Standardization of Breast Radiotherapy Trials (START), presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held in San Antonio, Texas, December 4-8, shows that appropriately dosed hypofractionated radiotherapy was gentle on healthy tissues and effective in controlling local-regional early breast cancer.

?Long-term follow-up 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,? said John Yarnold, M.B.B.S., professor of clinical oncology at The Institute of Cancer Research in London and honorary consultant at The Royal Marsden NHSFoundation Trust. ?The risk of breast cancer recurring continues beyond five years, and side-effects of radiotherapy can often develop many years after treatment, so these long-term results provide a very important reassurance that the shorter treatment course is definitely the best option for patients. Some doctors may have been hesitant to change their practice on the basis of five-year results, but these long-term findings should convert those sceptics,” Yarnold noted.

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

Data revealed 139 local-regional tumor relapses among the 2,236 women in START A who were followed for an average of 9.3 years and 95 local-regional relapses in the 2,215 women in START B, followed for an average of 9.9 years. The 10-year local-regional 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 local-regional relapse rate was 5.5% after 50 Gy and 4.3% after 40 Gy.

?We have shown conclusively that less can be more in breast cancer radiotherapy. Three weeks of radiotherapy is as good as five weeks ? as well as being more convenient and less tiring for patients and cheaper for the health service.?

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Sensitive to Radiation
Low radiotherapy doses had traditionally been used as scientists had originally believed that normal healthy breast tissue was more sensitive than tumour cells to the effects of radiotherapy, and that therefore small daily doses of radiotherapy were gentler on healthy tissues than cancer. But the trial has confirmed that cancer cells are just as sensitive to radiotherapy dose as healthy tissue ? meaning that giving lower doses spared the cancer as much as the healthy tissue, and a higher dose could be more effective.

?These long-term data from the START A trial confirm the findings of our earlier results that breast cancer is, on average, as sensitive to the radiation dose of each fraction as the dose-limiting normal tissues of the breast area and that this effect persists for at least 10 years,? Yarnold said.

However, a five-week, 13-fraction schedule does not offer shortened overall treatment times. ?Hence, we also designed the START B trial, a pragmatic comparison of three-week and standard five-week schedules, testing for noninferiority,? said Yarnold. ?The 15-fraction schedule is definitely gentler on the healthy tissues, and these long-term data confirm our earlier findings that it appears noninferior in terms of tumor control ? a very favorable result.?

Standard of care
The three-week, 15-fraction schedule is now the standard of care in the United Kingdom and is becoming increasingly more common in other countries, according to Yarnold. Future research is focused on the molecular mechanisms that determine fraction size sensitivity, which may lead to individualization of fraction size.

?It is likely that some breast cancers are more or less sensitive than others,? Yarnold said. ?We are also testing a one-week schedule of whole breast radiotherapy against our new three-week standard in the U.K. FAST-Forward Trial.?

Jo Haviland, a senior statistician at The Institute of Cancer Research (ICR),presented the new START trial results at the CTRC-AACR San Antonio Breast Cancer Symposium today. Commenting on the trial results, she said: ?The START trial had a huge impact on changing the standard of care for women with breast cancer in the UK, and increasingly around the world. Recruitment is already underway for a major new 15-year-long UK trial we are co-ordinating, to see if we can further improve treatment and spare both women and the health system the burden of extra treatments.?.

The START trials were funded by Cancer Research U.K., the U.K. Medical Research Council and the U.K. Department of Health.

For more information:
NCT00005588– Standardisation of breast radiotherapy (START) trial

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