LOS ANGELES—A boost of radiation aimed at the tumor bed lowers the risk of ipsilateral breast tumor recurrence in early-stage breast cancer patients at high risk for local relapse due to high-grade tumors, positive surgical margins, or younger age, researchers reported here at the American Society for Therapeutic Radiology and Oncology Annual Meeting.
The radiation boost had its greatest effect in lowering the risk of local relapse in women age 40 and under, who are at greatest risk for ipsilateral breast tumor recurrence, said lead author Heather A. Jones, MD, Assistant Professor of Radiation Oncology at the University of Pittsburgh Cancer Center.
The study also showed that a high grade of invasive tumor or a high grade of ductal carcinoma in situ (DCIS) are more significant risk factors for ipsilateral breast tumor recurrence than margin status.
What this means, Dr. Jones said, is that women with high-grade tumors benefited even more from the boost then those whose cancer cells extended into the surgical margins.
“A boost dose of 16 Gy ameliorates the effects of involved margins and substantially lowers the risk of local recurrence in patients with high-risk features,” she said.
Boost vs No Boost
The new findings come from a substudy analysis of the European Organization for Research and Treatment of Cancer's (EORTC) landmark “Boost-No Boost Trial,” which lent credibility to the common practice of giving a boost of radiation to the tumor bed following standard 50-Gy whole-breast radiation.
The 10-year results of the trial, published earlier this year in the Journal of Clinical Oncology (Bartelink H et al: JCO 2007;25:3259–3265) showed that a 16-Gy boost dose of radiation to the tumor bed significantly improves local control in patients with early-stage breast cancer who undergo breast-conserving therapy.
The study involved 5,318 women who had been treated with microscopically complete excision followed by whole-breast irradiation of 50 Gy. They were then randomized to receive either a 16 Gy boost to the tumor bed or no boost.
The cumulative incidence of local recurrence at 10 years was 6.2% in the boost group vs 10.2% in the no-boost group, translating to a relative risk reduction of 41% in favor of the boost group.
However, severe fibrosis increased with the boost: 4.4% compared with 1.6% for no boost.
There was no significant difference in the 10-year overall survival rates among the two groups.
Dr. Jones said that radiation oncologists “use boosts quite a lot, even though there had never been a randomized controlled trial asking the question of whether a boost to the tumor bed works and is safe in the breast.
“We did know from other sites such as the head and neck that a boost to the bed works. Now we have the data to say it improves local control in early-breast cancer patients as well,” said Dr. Jones, who started working on the study while at the Netherlands Cancer Institute.
The new analysis was designed to tease out risk factors for local recurrence and determine which women benefited most from the extra dose, Dr. Jones explained.
For the substudy, the researchers analyzed tissue samples from 1,724 patients who participated in the EORTC trial. All had a central pathology review by one expert, and all had invasive tumor with or without accompanying DCIS evaluated.
The results showed that that if the margin of the tumor was involved, the risk of relapse at 10 years was 4% for women with invasive tumor who got the boost, compared with 13% for those who did not get the boost, a highly significant difference.
Among women with DCIS and margin involvement, the risk of relapse at 10 years was also significantly reduced by the boost: 6% vs 15% for those who did not get the boost.
If the margin was not involved, however, there was no significant difference in the risk of relapse between the boost and no-boost groups in women with either type of tumor, the study showed.
Dr. Jones said further analysis showed that tumor grade was a more important prognostic marker than margin status.
Among women with high-grade invasive excised tumors, the 10-year risk of local recurrence was 7% for those who got a boost, compared with 19% for those who didn't, a significant difference, she reported.
If the margin involved high-grade DCIS, the relapse risk at 10 years was 5% for boosted women vs 17% for women who didn't get a boost, again a significant difference.
The greatest reduction in the local recurrence rate, from 23.9% to 13.5%, was seen in patients age 40 or younger.
‘Confirms and Justifies’
Commenting on the findings, Shiv R. Khandelwal, MD, Assistant Professor in the Department of Radiation Oncology at the University of Virginia, said, “This confirms and justifies our existing practice patterns.”
The big issue now is the boost dose, he said. In the United States, radiation oncologists typically use a 10 Gy boost, compared with the 16 Gy used in the European study, he noted.
“These findings may result in some change in practice, with more physicians using the higher dose routinely, which means an extra one and a half weeks of treatment.”
The higher boost may also cause slightly more scarring, he noted.
Dr. Khandelwal said that in his view, the bigger dose should be used when the surgical margin is close, 2 mm or less.
“I consider ideal margins to be 5 mm or greater—and then I typically stop with a total of 60 Gy, or a 10 Gy boost,” he said.
Harry Bartelink, MD, PhD, Head of the Division of Radiotherapy at the Netherlands Cancer Institute, the lead author of the original EORTC trial, said that based on the findings, the Netherlands Cancer Institute has changed its protocol for the treatment of women with early-stage breast cancer who undergo breast-conserving surgery to include a 16 Gy boost of radiation to the tumor bed.
But, he added, they have altered the protocol so that the boost is integrated into the same time period as when they give the whole-breast irradiation.
Dr. Khandelwal said that one subset of women for whom the benefits of a boost are still unclear are patients who have undergone a successful reexcision to remove cancerous tissue from the margin left after the original excision.
“That was not looked at, and it's actually quite common,” he said, estimating that he sees a patient who fits that profile at least once a month.