Vaidya, Jayant S; Williams, Norman R; Bulsara, Max; Baum, Michael; Brew-Graves, Chris; Potyka, Ingrid; Roberts, Nicholas; ... Tobias, Jeffrey S; + view all Vaidya, Jayant S; Williams, Norman R; Bulsara, Max; Baum, Michael; Brew-Graves, Chris; Potyka, Ingrid; Roberts, Nicholas; Lindsay, Julie; Laws, Siobhan; Raj, Sanjay; Douek, Michael; Falzon, Mary; Petralia, Gloria; Malhotra, Anu; Needleman, Sarah; Bernstein, Marcelle; Morgan, David; Tobias, Jeffrey S; - view fewer (2025) Using targeted intraoperative radiotherapy for early breast cancer reduces the incidence of late-onset lung cancer: 25-year update from the TARGIT-A randomised trial. UCL (University College London): London, UK.

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Text Vaidya_Using TARGIT-IORT for breast cancer reduces the incidence of late-onset lung cancer compared with whole breast radiotherapy 1.pdf Download (672kB) | Preview

Abstract

Background: With improvement in survival after breast cancer, the burden and longer-term side effects of treatment are increasingly relevant. Today, most patients can avoid a mastectomy, but having a breast conserving surgery has traditionally been followed by external beam whole breast radiotherapy (EBRT), which can be onerous and leads to inevitable and potentially carcinogenic irradiation of nearby vital organs such as the lungs. / Setting and Method: The results of the TARGIT-A randomised trial found that targeted intraoperative radiotherapy (TARGIT-IORT) during the initial lumpectomy is as effective as EBRT in controlling breast cancer, and has several benefits to the patient including reduced pain, improved cosmetic outcome and quality of life, and significantly fewer deaths from non-breast-cancer causes, leading to an overall survival benefit in patients with grade 1 or 2 cancers with a 12-year mortality reduction from 15% to 10.5%. We collected long term data for health status and new diagnoses in the 714 UK patients who participated in the TARGIT-A randomised trial by using direct patient contact, and data from NHS records. For this paper, we analysed the comparative incidence of lung cancer as it has a well-established causal relationship with EBRT, to assess the magnitude of the difference between TARGIT-IORT and EBRT. / Results: Trial recruitment was from March 2000 to June 2012. The median follow up now is 12.4 years. There were significantly more new lung cancer diagnoses in the EBRT patients compared with TARGIT-IORT patients - HR 3.3 (95%CI 1.1-10.2), 16-year incidence: EBRT: 7.2% (95%CI 3.74 – 13.70) and TARGIT: 1.8% (95%CI 0.6-5.2), 5.38% excess lung cancers with EBRT (95%CI 0.3 -10.5), log rank p=0.0266. An estimated 920,000 breast cancer patients worldwide are suitable for TARGIT-IORT annually. Using the 5.38% reduction in lung cancer risk that we have observed, if TARGIT-IORT were to be made accessible to these patients, then 49496 (95%CI 5500-134320) of these patients would be spared the diagnosis of a lung cancer during their follow up. / Discussion: These new data from very long-term follow up of a large, randomised trial show a substantial increase in incidence of lung cancer with EBRT compared with TARGIT-IORT. It is a tragedy when women who outlive breast cancer then succumb to this frequently lethal (EBRT) radiation-induced second cancer, the which is avoidable by using TARGIT-IORT during lumpectomy instead of EBRT. These new data further mandate full discussion with patients about the benefits of TARGIT-IORT before their surgery, and enabling them to take it during their lumpectomy.

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