Time trends in cardiac doses in 10,000 patients receiving curative thoracic radiation therapy between 2009 and 2020

Background and purpose In the last 20 years, it has become well-documented that incidental cardiac exposure to ionizing radiation is associated with a clinically relevant increased risk of cardiovascular morbidity. In parallel, radiation therapy technologies have been developed to provide target dose coverage with less exposure to adjacent organs at risk. In the current work, we investigate trends in cardiac exposure among patients treated with curative intent radiotherapy from a single institution between 2009 to 2020. Materials and methods 10,215 treatment courses were analyzed from 9,966 patients treated with curative intent for intrathoracic or breast cancers in the period 2009-2020. All hearts were re-delineated using an AI model to ensure consistency over time. Cardiac doses were extracted in 3D from the record-and-verify system and converted, voxel-by-voxel, to equi-effective doses in 2 Gy fractions (EQD2) using α/β=2 Gy. Mean heart dose (in EQD2) and volume exposed to 5 and 40 Gy (V5 and V40Gy), respectively, were extracted. Time trends in these cardiac dose-volume metrics were investigated for each diagnosis. Results Patients with esophageal cancer had the highest mean heart dose (median = 11.67 Gy; IQR = 2.85, 18.18), while the lowest was observed in patients with breast cancer (median = 0.60 Gy; IQR = 0.30, 1.08) and lymphoma (median = 0.01 Gy; IQR = 0.00, 0.38). A decreasing trend over time was seen most clearly for patients with esophageal and lung cancers (p<0.05). Among patients with breast cancer, V40 decreased from 2009-2015 after which we observed an increase. Conclusion There has been a significant reduction in radiation exposure to the heart in patients treated in the period 2009-2020, likely due to increased awareness of cardiovascular toxicity and technological developments. The study also found a significant increase in V40 from 2015 to 2020 for patients with breast cancers, possibly related to increased prioritization of target coverage. Highlights ### Competing Interest Statement We report institutional research and teaching contracts with Brainlab, Varian, and ViewRay. ### Funding Statement This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 801199. The authors acknowledge support from Kirsten and Freddy Johansen's award and National Cancer Institute (Grant No. P30 CA 134274-04). SMB was supported by funds through the Maryland Department of Health's Cigarette Restitution Fund Program. IRV and JP received research funding from Varian Medical Systems. IRV and JP are supported by Danish Cancer Society (Grant No. R231-A13976). This work is supported by Danish National Research Foundation (DNRF) grant number 126 (PERSIMUNE). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Danish National Committee of Health Research Ethics (NVEK) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data produced in the present study are available upon reasonable request to the authors