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

Jayant S Vaidya, Max Bulsara, Michael Baum, Frederik Wenz, Samuele Massarut, Steffi Pigorsch, Michael Alvarado, Michael Douek, Christobel Saunders, Henrik Flyger, Wolfgang Eiermann, Chris Brew-Graves, Norman R Williams, Ingrid Potyka, Nicholas Roberts, Marcelle Bernstein, Douglas Brown, Elena Sperk, Siobhan Laws, Marc SütterlinTammy Corica, Steinar Lundgren, Dennis Holmes, Lorenzo Vinante, Fernando Bozza, Montserrat Pazos, Magali Le Blanc-Onfroy, Günther Gruber, Wojciech Polkowski, Konstantin J Dedes, Marcus Niewald, Jens Blohmer, David McReady, Richard Hoefer, Pond Kelemen, Gloria Petralia, Mary Falzon, David Joseph, Jeffrey S Tobias

Research output: Contribution to journalArticlepeer-review

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).

Original languageEnglish
Pages (from-to)380-389
Number of pages10
JournalBritish Journal of Cancer
Volume125
Issue number3
DOIs
Publication statusPublished - Aug 2021

Keywords

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

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