Intraoperative Radiotherapy Inferior to External Radiotherapy in Preventing Local Recurrence in Early Breast Cancer
A single session of intraoperative radiotherapy with electrons permits delivery of a radiotherapy dose equivalent to that of conventional postoperative whole-breast irradiation. In the ELIOT trial reported in The Lancet Oncology, Umberto Veronesi, MD, of the European Institute of Oncology, and colleagues investigated whether intraoperative radiotherapy could meet a local recurrence equivalence margin of 7.5% in patients with early breast cancer. Although the treatment was associated with a local recurrence rate within the equivalence margin, the rate was significantly greater than that with whole-breast external radiotherapy.
Study Details
In this unblinded study, 1,305 women aged 48 to 75 years with early breast cancer and a maximum tumor diameter of ≤ 2.5 cm who were candidates for breast-conserving surgery were randomly assigned to intraoperative radiotherapy (n = 651) or external radiotherapy (n = 654) between November 2000 and December 2007. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumor bed during surgery and patients in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy followed by a boost of 10 Gy in five fractions.
The prespecified equivalence margin was local recurrence rate of 7.5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumor recurrences. Overall, 96% of patients received adjuvant therapy, with 75% receiving endocrine therapy alone, 8% chemotherapy alone, and 14% both.
Recurrence Rates
After a median follow-up of 5.8 years, 35 patients in the intraoperative radiotherapy group and 4 patients in the external radiotherapy group had an ipsilateral breast tumor recurrence, yielding 5-year event rates of 4.4% vs 0.4% (hazard ratio = 9.3, P < .0001). Thus, although the rate of local recurrence in the intraoperative radiotherapy group was within the equivalence margin, it was significantly greater than the rate in the external radiotherapy group.
The intraoperative radiotherapy group also had significantly greater 5-year rates of local recurrence in the index quadrant (2.5% vs 0.4%, P = .0003), new ipsilateral breast tumors (1.9% vs 0%, P = .0001), axillary or other regional lymph node metastases (1.0% vs 0.3%, P = .03), and locoregional tumor recurrence (5.4% vs 0.8%, P < .0001). Rates of distant metastasis (5.1% vs 4.8%) and other primary cancers (2.5% vs 3.2%) did not significantly differ between the two groups.
There were no significant differences between the intraoperative radiotherapy and external radiotherapy groups in 5-year overall survival (96.8% vs 96.9%, P = .59), rate of death from breast cancer (2.1% vs 2.0%, P = .56), or rate of death from other causes (1.1% vs 1.1%, P = .93).
Skin Toxicity
Among patients with data available, any skin toxicity occurred in 8.0% of the external radiation group vs 2.7% of the intraoperative radiotherapy group (P = .0002). Erythema, dryness, hyperpigmentation, and pruritus were significantly more common in the external radiotherapy group, and fat necrosis was significantly more common in the intraoperative radiotherapy group.
The investigators concluded: “Although the rate of [ipsilateral breast tumor recurrence] in the intraoperative radiotherapy group was within the prespecified equivalence margin, the rate was significantly greater than with external radiotherapy, and overall survival did not differ between groups. Improved selection of patients could reduce the rate of [ipsilateral breast tumor recurrence] with intraoperative radiotherapy with electrons.”
The study was funded by the Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, and Umberto Veronesi Foundation.
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