Similar Late AEs Observed With Different Radiation Doses in Breast Cancer

Targeted Therapies in Oncology, December 2 2018, Volume 7, Issue 13

Women who received 5 fractions of 28.5 Gy over 5 weeks experienced similar adverse events as women who received 50.0 Gy in 25 fractions over 5 weeks, according to findings presented by A. Murray Brunt, MB, BS.

1Brunt is the chief investigator of the FAST trial, a long-term study that assessed changes in healthy breast tissue following conventional radiation therapy compared with 2 shorter regimens that delivered higher doses of radiation in fewer sessions.

Specifically, FAST followed 915 women with early invasive breast cancer, pT1-2 pN0, who were randomized to receive either 50.0 Gy of radiation delivered in 25 daily 2.0-Gy fractions over 5 weeks or hypofractionated treatment with 1 of 2 doses: 30.0 Gy delivered in 5 once-weekly fractions of 6.0 Gy each or 28.5 Gy delivered in 5 once-weekly fractions of 5.7 Gy each. Brunt shared the results during the 60th Annual Meeting of the American Society for Radiation Oncology.

“The profile of adverse events to normal breast tissue was similar between the 28.5-Gy and 50.0-Gy groups, but AEs were higher after 30.0 Gy was given in 5 fractions over 5 weeks,” said Brunt.

The women received annual clinical assessments for 10 years, accompanied by a photographic assessment that included skin reactions, hardening of the breast, and changes in breast conformation at 2 and 5 years after randomization (TABLE 1). The primary endpoint of the trial was 2-year changes in photographic breast appearance that were published previously,2with secondary endpoints focusing on 5-year change in photographic breast appearance, clinical assessments of late AEs, and ipsilateral local tumor control. “What I’m able to present today are the secondary endpoints,” he said.

The assessment was based on a 4-point scale in which changes were characterized as none, mild, moderate, or marked. “When mild and severe changes were compared, nearly all the changes were considered mild,” said Brunt. “Marked changes were reported at 2% [50.0 Gy], 4% [30.0 Gy], and 2% [28.5 Gy].” Brunt noted little change in prevalence of AEs between 5 and 10 years.

Initial results of the FAST trial indicated that once-weekly, hypofractionated therapy led to low normal tissue effects similar to those of conventional therapy at 2 years following treatment. The results of the current study confirm that these similarities persisted over the long term.

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%) at 5 years and 9 of the 392 women (2.3%) at 10 years.

The investigators noted that late normal tissue effects did not approach significance when the 50.0-Gy and 28.5-Gy groups were compared at the 5-year or 10-year interval. Patients who received 30 Gy, 5 fractions, experienced moderate or severe late effects to normal breast tissue. This cohort was 2 to 3 times more likely to experience moderate/severe instances of breast shrinkage (P <.001), hardness (P = .004), fluid buildup (P <.001), and spider veins (P = .02) than either the 28.5-Gy or 50.0-Gy cohorts.

Investigators noted normal tissue effects in 7.5% of patients who received the traditional, daily fraction at 5 years. At the 10-year interval, 9.1% of patients had normal tissue effects. In comparison, rates for the 5-fraction 30-Gy arm were 18.0% at 5 years (P <.001) and 18.4% at 10 years (P = .04), Brunt said.

Brunt explained that the differences between the regimens were a result of fractionation sensitivity. He noted that delivering 30.0 Gy in 5 fractions over 5 weeks is equivalent to a total radiation dose of 57.3 Gy delivered in 2.0-Gy fractions, while 28.5 Gy delivered in 5 fractions over 5 weeks is roughly the same as 52.5 Gy in 2.0-Gy fractions. Further, calculations suggest that 27.75 Gy delivered in 5 fractions over 5 weeks would be equivalent to 50.0 Gy in 25 fractions over 5 weeks.

The response of early-stage invasive breast tumors to surgery and radiation was also assessed, said Brunt. The investigators reported that the 10-year local relapse rate for all patients in the trial was 1.3% (95% CI, 0.7-2.3). Between the 2 treatment groups, only 10 AEs were reported (50.0 Gy, 3; 30.0 Gy, 3; 28.5 Gy, 4), and 96 deaths (50.0 Gy, 30; 30.0 Gy, 33; 28.5 Gy, 33) have been reported (TABLE 2).

“We can conclude that severe changes to normal breast tissue [were] quite a rare finding in any of the arms. The late AEs for the 28.5-Gy arm [were] similar to [those of] the 50.0- Gy arm,” said Brunt. “Local tumor relapse is low in all 3 arms, so a once-weekly schedule could be considered for patients for whom the 5 weeks or, perhaps, now the 3-week schedule is an option.

“[Our research] has moved on to the UK FAST-Forward trial, which is investigating delivering 5 fractions in 1 week,” Brunt concluded.

References:

  1. Brunt Am, Haviland, J, Sydenham M, et al. FAST phase III RCT of radiation therapy hypofractionation for treatment of early breast cancer: 10-year results (CRUKE/04/015). Presented at: 60th Annual Meeting of the American Society for Radiation Oncology; October 21-24, 2018; San Antonio, TX. Abstract LBA2.
  2. Agrawal RK, Alhasso A, Barrett-Lee PJ, et al; FAST Trialists group. First results of the randomised UK FAST trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol. 2011;100(1):93-100. doi: 10.1016/j.radonc.2011.06.026.