Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial

Abstract

ObjectiveTo determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.DesignProspective, open label, randomised controlled clinical trial.Setting32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.Participants2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).InterventionsRandom allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).Main outcome measuresNon-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.ResultsBetween 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% 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), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).ConclusionFor patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.Trial registrationISRCTN34086741, NCT00983684.

Intraoperative radiotherapy for breast cancer: powerful evidence to change practice

“…The TARGIT-A randomized trial compared risk-adapted TARGIT-IORT with WBRT. The long-term results 2 revealed no significant differences in local and distant control, breast preservation or breast cancer mortality. Local control was also comparable to that achieved with TARGIT-IORT alone 2 .…”

“…The long-term results 2 revealed no significant differences in local and distant control, breast preservation or breast cancer mortality. Local control was also comparable to that achieved with TARGIT-IORT alone 2 . A significant reduction in non-breast cancer mortality (from cardiovascular causes and other cancers) was also observed with TARGIT-IORT, from 9.85% to 4.41% at 12 years 2 .…”

“…17 , 723–724 (2020)) 1 about the TARGIT-A trial contains several factual and logical errors. This article overlooks both the long-term positive findings 2 and the all-important patient perspective.…”

“…Risk-adapted single-dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) is a method of partial breast irradiation (PBI) for early breast cancer. Most patients (80%) receiving TARGIT-IORT 2 during their lumpectomy complete their local treatment entirely during this single session, under the same anaesthetic. Supplemental whole breast external beam radiotherapy (WBRT) is only recommended for a minority of patients (20%) if unexpected prespecified tumour-related factors such as invasive lobular cancer and positive margins are found postoperatively.…”

“…By contrast, traditional WBRT or other PBI approaches require up to 30 additional hospital visits — TARGIT-IORT involves far fewer clinic appointments 3 . Other benefits include fewer toxicities, less pain, better cosmetic results and better quality of life 2 .…”