Sep 30

SS 46 - Right-Sizing Radiation in Early Breast Cancer: Omission, Shortening, and Targeted Approaches

349 - Initial Outcome Of The TARGIT-B International Randomised Trial Of Targeted Intraoperative Radiotherapy Tumour Bed Boost For Young Or High-Risk Patients With Breast Cancer

09:15am - 09:25am ET

Room 258

Presenter(s)

Jayant Vaidya, MD, MB, PhD, FRCS - University College London, London, Camden

J. S. Vaidya¹, M. K. Bulsara², J. S. Tobias³, N. R. Williams⁴, C. Brew-Graves¹, M. Douek^5,6, J. Jeong⁷, C. A. Benn⁸, Y. Ramdas⁹, S. Massarut¹⁰, L. Vinante¹¹, S. Mee Hoong¹², N. A. Mohd Talib¹², B. Pinar¹³, P. C. Lara¹⁴, S. Talomo¹⁵, M. Krengli¹⁶, E. Martin¹⁷, G. Petralia^18,19, M. Abdelhadi²⁰, F. Guedea²¹, E. Martinez²², J. Singer²³, N. Coombs²⁴, F. Izar²⁵, M. Le Blanc-Onfroy²⁶, A. Petit²⁷, S. Needleman²⁸, S. Denariyakoon²⁹, X. Wang³⁰, and P. Kelemen³¹; ¹University College London, London, United Kingdom, ²Institute for Health Research, University of Notre Dame, Fremantle, Australia, ³University College London Hospitals, London, United Kingdom, ⁴UCL, London, United Kingdom, ⁵University of Oxford, Oxford, United Kingdom, ⁶Guy's Hospital, London, United Kingdom, ⁷Department of Surgery, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), ⁸Netcare Breast Care Centre of Excellence, Johannesburg, South Africa, ⁹University of Witwatersrand, Johannesburg, South Africa, ¹⁰Centro di Riferimento Oncologico of Aviano, Aviano, Italy, ¹¹Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano, Italy, ¹²Universiti Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia, ¹³Hospital Universitario de Gran Canaria Dr Negrín, Gran Canaria, Spain, ¹⁴San Roque University Hospital/Fernando Pessoa Canarias University, Las Palmas de Gran Canaria, Spain, ¹⁵Veneto Institute of Oncology IOV IRCCS, Padua, Italy, ¹⁶University of Piemonte Orientale, Novara, Italy, ¹⁷Université Bourgogne Europe, Centre Georges-François Leclerc, Unicancer, Radiation Oncology Department, Dijon, France, ¹⁸Oxford University Hospital, Oxford, United Kingdom, ¹⁹Whittington Hospital, London, United Kingdom, ²⁰Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, ²¹University of Barcelona, L'Hospitalet-Barcelona, Spain, ²²Institut Català d’Oncologia (ICO), Barcelona, Spain, ²³Princess Alexandra Hospital, Harlow, United Kingdom, ²⁴Great Western Hospital, Swindon, United Kingdom, ²⁵Universitaire du cancer de Toulouse Oncopole, Toulouse, France, ²⁶Institute de Cancerologie de l'Ouest René Gauducheau, Nante, France, ²⁷Institut Bergonié, Bordeaux, France, ²⁸Royal Free Hospital, London, United Kingdom, ²⁹Queen Sirikit Centre, Bangkok, King Chulalongkorn Memorial Hospital, Bangkok, Thailand, ³⁰Beijing Cancer Hospital, Beijing, China, ³¹Northwell Health, Sleepy Hollow, NY

Purpose/Objective(s): The TARGIT-A trial (inclusion: age >45 years) had already shown that single-dose targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy, vs whole breast external beam radiotherapy (EBRT), led to equivalent breast cancer control and fewer deaths. Laboratory and trial data suggested a systemic (abscopal) beneficial effect of TARGIT-IORT, potentially via the abrogation of the tumor-stimulating effects of surgical wounding and immune stimulation. Younger patients face a higher risk of relapse, and TARGIT-IORT-Boost could improve outcomes in a cohort complementary to the TARGIT-A trial.

Materials/Methods: The TARGIT-B international trial randomized patients who were young (=45 yrs) or, if older, with high-risk tumors, from 2013 - 2022 to TARGIT-IORT-Boost during surgery, or postoperative EBRT-Boost. Whole breast radiotherapy was planned for all patients. We analyzed the local relapse, distant relapse and survival.

Results: A total of 1684 patients were randomized: 848 to TARGIT-IORT-Boost and 836 to EBRT-Boost, from 35 centers in 12 countries from Europe, Asia, Africa and North America. They were young, and high-risk cases: one-third, n=544, were young (=45 years), and a substantial proportion had high-risk tumors (e.g., grade 3, post-neoadjuvant). At median follow-up of 4.2 years, local recurrence was low and overall survival high in both arms (4-year Kaplan-Meier estimates: 2·3% vs. 2·1% and 94·6% vs 94·1%). Distant relapses were fewer with TARGIT-IORT-Boost: (33/848 vs 46/836, HR 0·68 [95%CI 0·43 – 1·06] p=0·087), especially after 2 years: HR 0.48 (0.25 – 0.92) p=0.0225.

This beneficial systemic effect of TARGIT-IORT-Boost on distant metastatic relapse was clinically substantial and statistically highly significant in the 544 young patients aged =45 years: 4-year distant relapse: 3·6% vs 8·8%, and 7-year distant relapse: 4·3% (95%CI 2·3 – 8·0) vs 17·0% (95%CI 10·5 – 26·7), HR 0·33 (0·16 – 0·68) p=0·0016.

TARGIT-IORT significantly improved relapse-free survival in young patients: at 4 years 92·0% (87·8 – 95·8) vs 87·3% (81·9 – 91·2), and 7-years: 89·5% (84·1 – 93·1) vs 78·5% (69·1 – 85·4), HR 0·57 (95%CI 0·24 – 0·97) p=0·037.

For the entire trial population, distant relapse after local recurrence was also significantly lower with TARGIT-IORT-Boost, HR 0·32 (95%CI 0·12 – 0·89) p=0·03.

Conclusion: These are the first randomized data supporting TARGIT-IORT-Boost as the preferred radiation option in young patients, enabling a three-fold reduction in distant metastatic relapse.

For women >45 years, the TARGIT-A trial confirmed equivalent breast cancer control, with significantly fewer deaths from non-breast-cancer causes, and improved overall survival for grade 1 or 2 cancers.

The TARGIT-A and TARGIT-B data taken together support using TARGIT-IORT during lumpectomy as a treatment option across all ages and risk, with additional EBRT if required, providing better quality of life, fewer distant metastatic relapses, reduced mortality and lower overall cost.