ASTRO: Radiation Boost Lowers Breast Cancer Relapse Risk

LOS ANGELES, Oct. 31 -- Two factors increase the risk of relapse after lumpectomy for early-stage breast cancer, but a boost of radiation aimed at the tumor bed lowers that risk, researchers reported here. A high-grade invasive tumor or a high-grade ductal carcinoma in situ (DCIS) in the margins of the resected tumor both increase the risk of later relapse, according to Heather Jones, M.D., of the University of Pittsburgh, and colleagues.
But they've found that a boost of radiation aimed at the tumor bed lowers the risk of relapse even for high-risk women, Dr. Jones said at the American Society for Therapeutic Radiation and Oncology meeting.
The findings come from a secondary analysis of the European Boost-No Boost trial, a long-term randomized controlled trial that showed that an extra dose of radiation significantly reduces the risk of local relapse.
The original study, published earlier this year in the Journal of Clinical Oncology, showed that the risk of relapse was 7% after 10 years if women got the extra dose, compared with 12% without the boost.
It was confirmation that the widely used practice of boosting standard 50-Gray whole-breast radiation with 16 Gray aimed at the tumor bed actually offers a significant benefit, Dr. Jones said.
But to find out which women benefited most from the extra dose, the researchers analyzed tissue from a third of the 5,318 women in the larger randomized trial, said Dr. Jones, who became involved in the study during a fellowship at the Netherlands Cancer Institute in Amsterdam.
The study found that if the margin of the tumor was involved, the 10-year risk of relapse was 4% for women who got the boost, compared with 13% for those who did not, a difference that was significant at P=0.0001.
On the other hand, when the margin was not involved there was no significant difference in the risk of relapse, Dr. Jones said.
But more important on a multivariate analysis was the type of tumor resected and the type of tissue remaining in the margins. Specifically:
If the excised tumor proved to be high-grade invasive, the 10-year risk of relapse was 7% for those who were boosted and 19% for those who weren't, which was significant at P=0.002.
If the margin included DCIS, the relapse risk was 5% for boosted women and 17% for unboosted, which was significant at P<0.0001.
Also, women 40 or younger who were boosted had the largest absolute risk reduction -- 23.9% versus 13.5% -- which was significant at P=0.0014, Dr. Jones said.
"The boost dose reduces the effect of margin involvement and it substantially reduces the risk of local recurrence in our high-risk patients," she said.
The Netherlands Cancer Institute has changed its clinical practice to include an extra 16 Gray of radiation aimed at the tumor bed in the wake of the trial, said Harry Bartelink, Ph.D., a radiation oncologist there.
But Dr. Bartelink, the study's senior author, said he and colleagues have re-arranged the protocol to include the extra dose during the same time period as the standard 50-Gray whole-breast irradiation.
The study "confirms our existing practice, which I think is important," said Shiv Khandelwal, M.D., of the University of Virginia in Charlottesville, who was not part of the study.
Dr. Khandelwal said radiation oncologists in the U.S. tend to use a slightly lower radiation dose for the boost -- 10 Gray versus 16 in the European study -- and it may be that physicians here will now start using the higher dose.
On the other hand, he said, his practice is to use the higher dose in cases where the surgical margin around the tumor is close, defined as two millimeters or less.
One area that remains unclear is how to treat patients who undergo re-excision because the original surgical margin includes cancerous tissue, he said. If the re-excised tissue is free of cancer -- a common finding, Dr. Khandelwal said -- it's not clear if the radiation boost is needed.
The study was supported by the European Organization for Research and Treatment of Cancer. Dr. Jones said she had no conflicts.Primary source: International Journal of Radiation Oncology * Biology * PhysicsSource reference: Jones H, et al "The Impact of Boost Dose and Margins on the Local Recurrence Rate in Breast Conserving Therapy: Results From the EORTC Boost-No Boost Trial" Int J Rad Onc 2007; 69(3) Supplement S: S2.