A 10-year study of women with early-stage breast cancer has demonstrated that patients receiving fewer, higher radiation doses experienced similar adverse effects to healthy breast tissue as those undergoing conventional radiotherapy. The results, presented this week at the ASTRO Annual Meeting, indicate that treatments involving fewer hospital visits can be employed without increasing the risk of long-term side effects.
“This study says it’s possible to find a regimen that would allow early-stage breast cancer patients to be treated only once a week over five weeks rather than daily over the same time period,” explains lead author Murray Brunt, from University Hospitals of North Midlands and Keele University. “Findings should help doctors discuss risks and benefits with their patients for various courses of radiation therapy and inform shared decision-making between physicians and patients.”
Brunt reported the long-term results of the FAST clinical trial, led by the Institute of Cancer Research. The trial enrolled 915 women with early-stage invasive breast cancer at 18 UK centres from 2004 to 2007. Initial results indicated that hypofractionated therapy led to similarly low normal tissue effects as conventional therapy at two years following treatment (Radiother. Oncol. 10.1016/j.radonc.2011.06.026). The current study confirms that these similarities persist for an additional eight years.
Conventional versus hypofractionation
Patients in the trial underwent breast-conserving surgery and were then randomly assigned to one of three whole-breast radiotherapy schedules: 50 Gy delivered in 25 daily 2 Gy fractions over five weeks (conventional treatment); 30 Gy delivered in five once-weekly 6 Gy fractions; or 28.5 Gy in five once-weekly 5.7 Gy fractions. Patients were evaluated annually for normal tissue effects.
The research team observed low rates of moderate or severe long-term normal tissue effects for all treatment groups. They reported that severe side-effects occurred in 1.7% of 774 women with follow-up data at five years, and 2.3% of 392 women with follow-up data at 10 years.
Late normal tissue effects were similar for the conventional and the five-fraction 28.5 Gy group at five or 10 years. However, moderate/severe late effects to normal breast tissue were higher for the five-fraction 30 Gy regimen. Among patients on the conventional arm, physicians observed normal tissue effects in 7.5% and 9.1%, at five and 10 years, respectively; rates for the five-fraction 30 Gy arm were 18.0% and 18.4%, at five and 10 years.
“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,” says 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.”
The 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,” explains 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.”
