A 10-year study indicates that larger amounts of radiation delivered in fewer doses to early-stage breast cancer patients following surgery are just as safe in the long-term as administering multiple small doses of radiotherapy.

Researchers at the Institute of Cancer Research, London assert that decreasing total dose of radiation and administering it in five large fractions once a week to such patients results in similarly low rates of side effects in the long-run as 25 daily doses administered over the same period of time. Their claim is based on the 10-year findings of the FAST trial.

“By reducing the number of daily doses of radiotherapy required from 15 doses in 3 weeks to 5 doses in a single week, this significantly reduces the workload in all radiotherapy centers, thereby reducing waiting times not just for breast cancer patients but for all other patients requiring radiotherapy," Dr. Navita Somaiah, clinician scientist and team leader in the division of radiotherapy and imaging at the Institute of Cancer Research told HCB News. "It also releases capacity for offering more complex radiotherapy where needed. There are significant health economic benefits to the NHS, including cost savings and improved patient experience.”

Launched in 2004, the FAST trial compared radiotherapy schedules of fewer but larger fractions overall, with total dose of radiation decreased. The aim was to determine which course could reduce side-effects of radiotherapy the most. The three-year results of the trial, published in 2011, showed reducing the number of radiotherapy fractions to five was possible and safe in the short-term. The 10-year findings now confirm it to be safe in the long-term, with side effects remaining low a decade later.

The trial included 915 women with early-stage breast cancer from 19 centers across the U.K. Following breast cancer surgery, each was assigned to undergo either a regimen of daily doses or one of two courses in which five larger doses would be administered once a week. Each course was held over a period of five weeks. The standard regimen used the now outdated international standard of 50 Gy of radiation, divided into 25 daily doses of 2 Gy. One trial treatment used 30 Gy once a week in fractions of 6 Gy and the other used 28.5 Gy once a week in fractions of 5.7 Gy.

Researchers assessed the women annually for up to 10 years after their radiotherapy regimens ended, checking for side effects to healthy breast tissue such as hardening of the breast, swelling, skin reactions and changes in breast size.

Moderate or severe long-term effects were low across the treatment groups, with 86% of women experiencing no changes or minor changes in their healthy breast tissue after 10 years. The most common effect was breast shrinkage. Moderate or marked effects were two thirds more likely to occur in women on the 30 Gy regimen than those with the 50 Gy. Women on the 28.5 Gy regimen had a similar risk of moderate or marked effects to those on the 50 Gy.

Researchers concluded that using 28.5 Gy in five fractions once a week is safe in the long-term for certain patients, such as those who are frail or have chronic conditions.

“Our findings support treatment options that are more convenient for patients who cannot tolerate long courses of daily radiation, without increasing the risk of long-term side effects,” professor John Yarnold, chief investigator of the FAST trial, professor of clinical oncology at the ICR, and honorary consultant at the Royal Marsden NHS Foundation Trust, said in a statement. “The FAST trial confirms the safety of a radiotherapy course consisting of a lower total dose of radiotherapy delivered in five fractions of radiation. FAST has also laid the groundwork for the FAST-Forward trial, testing an even shorter treatment course of five fractions of breast radiotherapy delivered in a single week, which is likely to become a U.K. standard for patients with early breast cancer.”

FAST-Forward is a phase three, multicenter, randomized controlled trial that seeks to evaluate the effectiveness and safety of delivering five fractions of radiotherapy daily for one week, instead of the current U.K. standard of administering 15 fractions after primary surgery for early-stage breast cancer.

The FAST trial has already made an impact in not just the U.K. but the international stage as well, according to Somaiah. "This trial has already had a major impact both in the U.K. and internationally. Normally trials go through NICE approval before national guidelines are changed. However, the unprecedented circumstances in relation to COVID-19, have led to rapid adoption of this treatment schedule in order to safely treat breast cancer patients during the pandemic. The expectation is that this will become standard of care for early breast cancer patients in the very near future.”

The 10-year results of the FAST trial were funded by Cancer Research UK.

The results were published in the Journal of Clinical Oncology.