TARGIT-A (targeted intraoperative radiotherapy)

TARGIT-A randomised 2,298 women aged 45 or over with invasive ductal carcinoma up to 3.5 cm at 32 centres in ten countries between 2000 and 2012, before lumpectomy, to risk-adapted targeted intraoperative radiotherapy or to external beam radiotherapy. Intraoperative treatment was delivered immediately after the lumpectomy under the same anaesthetic and was the only radiotherapy about 80 percent of those patients received; the remaining fifth had external beam treatment added when postoperative pathology found unsuspected higher-risk features.

The trial met its non-inferiority margin of 2.5 percent: local recurrence risk at five years with complete follow-up was 2.11 percent with intraoperative treatment against 0.95 percent with external beam, a difference of 1.16 percent (90 percent confidence interval 0.32 to 1.99). In the first five years there were thirteen more local recurrences (24 of 1,140 against 11 of 1,158) and fourteen fewer deaths (42 against 56).

At a median 8.6 years, nothing separated the arms on local recurrence-free survival (hazard ratio 1.13, 95 percent confidence interval 0.91 to 1.41, p=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, p=0.74), distant disease-free survival (0.88, 0.69 to 1.12, p=0.30), overall survival (0.82, 0.63 to 1.05, p=0.13) or breast cancer mortality (1.12, 0.78 to 1.60, p=0.54). One endpoint did separate them: mortality from other causes was lower with intraoperative treatment (0.59, 0.40 to 0.86, p=0.005), which the investigators attribute to sparing the heart and lung.

England did not adopt it. NICE TA501, published on 31 January 2018, recommends that the Intrabeam system is not used for routine commissioning, and permits it only on machines already installed and under NHS England clinical governance and data collection arrangements. The record is marked mixed because the trial met its own margin while the regulator that read it declined to fund the device.