- 作者：Umberto Veronesi ; Roberto Orecchia ; Patrick Maisonneuve ; Giuseppe Viale ; Nicole Rotmensz ; Claudia Sangalli ; Alberto Luini ; Paolo Veronesi ; Viviana Galimberti ; Stefano Zurrida ; Maria Cristina Leonardi ; Roberta Lazzari ; Federica Cattani ; Oreste Gentilini ; Mattia Intra ; Pietro Caldarella ; Bettina Ballardini
- 刊名：Lancet Oncology
- 出版年：December, 2013
- 年：2013
- 卷：14
- 期：13
- 页码：1269-1277
- 全文大小：223 K
Summary
Background
Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery. However, its ability to control for recurrence of local disease required confirmation in a randomised controlled trial.Methods
This study was done at the European Institute of Oncology (Milan, Italy). Women aged 48-75 years with early breast cancer, a maximum tumour diameter of up to 2路5 cm, and suitable for breast-conserving surgery were randomly assigned in a 1:1 ratio (using a random permuted block design, stratified for clinical tumour size [<1路0 cm vs 1路0-1路4 cm vs 鈮?路5 cm]) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons. Study coordinators, clinicians, and patients were aware of the assignment. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery. Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy, followed by a boost of 10 Gy in five fractions. This was an equivalence trial; the prespecified equivalence margin was local recurrence of 7路5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumour recurrences (IBTR); overall survival was a secondary outcome. The main analysis was by intention to treat. This trial is registered with , number .
Findings
1305 patients were randomised (654 to external radiotherapy and 651 to intraoperative radiotherapy) between Nov 20, 2000, and Dec 27, 2007. After a medium follow-up of 5路8 years (IQR 4路1-7路7), 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR (p<0路0001). The 5-year event rate for IBRT was 4路4% (95% CI 2路7-6路1) in the intraoperative radiotherapy group and 0路4% (0路0-1路0) in the external radiotherapy group (hazard ratio 9路3 [95% CI 3路3-26路3]). During the same period, 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died (p=0路59). 5-year overall survival was 96路8% (95% CI 95路3-98路3) in the intraoperative radiotherapy group and 96路9% (95路5-98路3) in the external radiotherapy group. In patients with data available (n=464 for intraoperative radiotherapy; n=412 for external radiotherapy) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group (p=0路0002).
Interpretation
Although the rate of IBTR 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 IBTR with intraoperative radiotherapy with electrons.
Funding
Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, and Umberto Veronesi Foundation.