Appropriately dosed hypofractionated radiotherapy was gentle on healthy tissues and effective in controlling local-regional early breast cancer, according to 10-year follow-up results from the UK Standardization of Breast Radiotherapy Trials (START).

“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 5-week schedules of curative radiotherapy in women with early breast cancer,” said John Yarnold, MBBS, professor of clinical oncology at The Institute of Cancer Research in London and honorary consultant at The Royal Marsden NHS Foundation Trust.

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, 50 Gy of postsurgery radiotherapy given in 25 fractions for 5 weeks was compared with 41.6 Gy or 39 Gy in 13 fractions for 5 weeks. In START B, 50 Gy in 25 fractions for 5 weeks was compared to 40 Gy in 15 fractions for 3 weeks.

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The 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 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. Previously published data from START B reported that the 10-year local-regional relapse rate was 5.5% after 50 Gy and 4.3% after 40 Gy.

“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 5-week, 13-fraction schedule does not offer shortened overall treatment times. “Hence, we also designed the START B trial, a pragmatic comparison of 3-week and standard 5-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.”

Now, the 3-week, 15-fraction schedule is the standard of care in the United Kingdom, and Yarnold stated that it is becoming increasingly more common in other countries. 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 1-week schedule of whole breast radiotherapy against our new 3-week standard in the UK FAST-Forward Trial.”

This study was presented at the San Antonio Breast Cancer Symposium held December 4-8, 2012.