Rates of moderate or severe long-term effects to normal tissue were low across all treatment groups. Severe effects were observed in 13 of the 774 women (1.7 percent) with follow-up data at five years, and nine of the 392 women (2.3 percent) with follow-up data at 10 years. No changes or minor changes in normal tissue were observed in 88 and 86 percent of women at the five- and 10-year marks, respectively.

Late normal tissue effects were not statistically different between the conventional therapy group and the five-fraction 28.5 Gy group at five years or 10 years following treatment. Moderate/severe late effects to normal breast tissue were higher, however, for patients who received the five-fraction, 30-Gy regimen. These patients were two to three times more likely to experience moderate/severe instances of breast shrinkage (p<0.001), hardness (p=0.004), fluid build-up (p<0.001) and spider veins (p=0.02).


Among patients on the conventional, daily-fraction arm, physicians observed normal tissue effects in 7.5 percent at five years and 9.1 percent at 10 years. By comparison, rates for the five-fraction 30-Gy arm were 18.0 percent at five years (p<0.001) and 18.4 percent at 10 years (p=0.04).

“The profile of adverse effects to normal breast tissue was similar between the 28.5 Gy and 50 Gy groups, but rates were higher after 30 Gy given in five fractions over five weeks,” said Prof. Brunt. “This disparity is rooted in differences between the two regimens in fractionation sensitivity. The sensitivity of 30 Gy delivered in five fractions over five weeks was equivalent to a total radiation dose of 57.3 Gy in 2 Gy fractions, while 28.5 Gy delivered in five fractions over five weeks was roughly the same as 52.5 Gy in 2 Gy fractions.” Calculation suggests that 27.75 Gy delivered in five fractions over five weeks would be equivalent to 50 Gy in 25 fractions over five weeks.

Researchers also assessed how the early-stage invasive breast tumors responded to surgery and radiation. The 10-year local relapse rate for all patients in the trial was 1.3 percent (95% CI 0.7, 2.3), with only 10 events reported in total, balanced between the treatment groups. The trial was not designed to test differences in relapse rates between treatment groups.

Following these results, the research team is now investigating radiation therapy with five fractions delivered over five consecutive days. “As a next step, we want to investigate shortening the radiation therapy schedule to one week,” explained Prof. Brunt. “A schedule like this would have significant clinical and practical implications, such as allowing radiation therapy to be integrated more closely with surgery and other therapies.”

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