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

Br J Cancer. 2021 Aug;125(3):380-389. doi: 10.1038/s41416-021-01440-8. Epub 2021 May 25.

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).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Breast Neoplasms / surgery*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / radiotherapy*
  • Carcinoma, Ductal, Breast / surgery*
  • Combined Modality Therapy
  • Female
  • Humans
  • Intraoperative Care
  • Mastectomy, Segmental / methods*
  • Middle Aged
  • Prognosis
  • Survival Analysis
  • Treatment Outcome
  • Tumor Burden
  • Whole-Body Irradiation

Associated data

  • ClinicalTrials.gov/NCT00983684