ESTRO 2025 - Abstract Book

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Invited Speaker

ESTRO 2025

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Speaker Abstracts Cardiac toxicity in breast irradiation: Does it still burn? Debunking radiotherapy stigma Anne Crijns Radiation Oncology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands Abstract: In 2013, Darby et al. established a linear dose-effect relationship between mean heart dose (MHD) and the risk of acute coronary events (ACE), a finding subsequently validated by multiple studies. Since then, modern photon radiotherapy techniques, including deep inspiration breath hold (DIBH) and volumetric modulated arc therapy (VMAT), have significantly reduced MHD in patients with left-sided breast cancer, likely decreasing cardiac toxicity risks. However, despite these advancements, some patients still experience progression of subclinical coronary artery calcification or a sustained reduction in left ventricular global longitudinal strain, as highlighted by the MEDIRAD study (Euratom Research and Training Programme 2014–2018 No. 755523). Certain patients remain at high risk for cardiac toxicity due to systemic therapies, pre-existing cardiac conditions, or unfavorable radiotherapy parameters such as challenging anatomy, boost irradiation, or internal mammary chain irradiation. These individuals may particularly benefit from proton radiotherapy (PRT), which can substantially reduce MHD. In the Netherlands, PRT eligibility is determined by a predicted reduction of ≥2% in lifetime excess ACE risk based on the Darby model. Approximately 5% of breast cancer patients qualify for PRT; these individuals are typically younger, present with higher-stage disease, have multiple risk factors for ACE,combined with a relatively high cardiac dose. During this lecture, the updated results of model-based selection for proton therapy in breast cancer patients treated at the University Medical Center Groningen will be presented. Reducing cardiac dose is not only critical for minimizing cardiotoxicity but may also impact survival. In a retrospective cohort study of 3,423 breast cancer patients, we found that the effective dose to immune cells (EDIC), calculated as the equivalent uniform dose of MHD, mean lung dose (MLD), and doses to large and small blood vessels while accounting for blood flow and fractionation effects, was associated with worse breast cancer-specific survival. Even after adjusting for confounding factors in a multivariable Cox model, higher EDIC correlated with poorer outcomes. This effect may be partially mediated by reducing the risk of lymphopenia, which is linked to radiation exposure to lymphocyte-rich organs such as the heart, lungs, and liver. Interestingly, both breast cancer-specific and overall survival were similar in patients with right- and left-sided breast cancer, despite significant differences in MHD and MLD. However, as EDIC was similar in both groups, the question arises as to whether immune cell exposure to radiation may explain differences in survival outcome as well. Further investigations are needed to evaluate the impact of irradiated volume and low dose exposure to other organs beyond the relationship between heart dose and cardiac toxicity. Despite advancements in radiotherapy techniques, lingering concerns about radiation-related toxicity continue to affect patient and clinician perceptions. Breaking the stigma surrounding radiotherapy requires continued refinement of treatment and dose optimization strategies to minimize the impact of both cardiac dose as well as dose to other parts of the body to reduce toxicity while maintaining or even improving oncologic efficacy.

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Speaker Abstracts Overview of existing solutions and research Katia Parodi Department of Experimental Physics - Medical Physics, Ludwig-Maximilians-University Munich, Munich, Germany