New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer

Abstract

Background The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. Methods In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0–N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. Results Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt. Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17–0.88) P = 0.0091. Conclusion TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. Trial registration ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Targeted Intraoperative Radiotherapy (TARGIT-IORT) for Early-Stage Invasive Breast Cancer: A Single Institution Experience

“…The 2.1% IBTR rate is similar to the TARGIT-A trial, which demonstrated a 2.11% rate of IBTR with a 5-year complete follow-up (9). This is despite 40% of patients having a change in their ASTRO APBI CG suitability group pre to post-operatively and consistent with more recent subgroup analysis from the TARGIT-A trial suggesting that there is no difference in the local control achieved by TARGIT-IORT and EBRT, irrespective of tumor size or subtype (12). Similar to the TARGIT-A trial 17.3% of patients received additional WBI, most of whom were classified as unsuitable postoperatively.…”

The Abscopal Effect: A Review of Pre-Clinical and Clinical Advances

“…Recently reported data from the TARGIT-A trial, a risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer, showed IORT to be as effective as whole-breast external beam radiotherapy (EBRT) [82]. Vaidya et al presented further detailed analyses of the trial and concluded that TARGIT-IORT is as effective as EBRT in all subgroups for local recurrence-free survival (HR 0.75; 95% CI 0.57-1.003; p = 0.052) and overall survival (HR 0.96; 95% CI 0.68-1.35; p = 0.80) [83]. One of the striking findings was that unlike EBRT where local recurrence was a powerful predictor of distant metastases, breast cancer mortality and overall mortality, local recurrence following IORT did not have worse survival outcomes, suggesting possible action at a distance.…”

Long-Term Outcomes of an International Cooperative Study of Intraoperative Radiotherapy Upfront Boost With Low Energy X-Rays in Breast Cancer

“…An immediate downregulation of surgically induced tumor-growth factors could potentially yield improved disease-control outcomes, overcoming a temporal miss factor ( 23 – 25 ). Recent data have suggested an improvement in breast cancer mortality for those patients undergoing IORT; nevertheless, different confusing factors might be associated with these differences and further research is warranted to confirm this statement ( 13 , 26 ). An interesting feature related to this cohort was the time elapsed between IORT and EBRT start.…”