SAN ANTONIO – , suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.
At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.
Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.
“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
Implications for practice and research
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.
“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”
Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”
It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.
The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”