Abstract
Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.
Highlights
Over 17 million cases of cancer were diagnosed worldwide in 2018, and roughly 9.5 million cancer deaths were reported [1]
More advanced techniques anddeveloped modalitiestosuch as intensity-modulated radiation therapy other non-commercial systems have been deliver localized, image-guided radiotherapy (IMRT) andThese protonimage therapy have systems not beenare extensively explored in, toxicity models, modern small animal irradiators can allow for arc therapy and this technique which allow the systems to deliver high doses to small, targeted regions [54,60] and aim to mimic is beginning to be utilized clinical
These results demonstrated that the Brown Norway (BN) rat chromosome 3 contains one or more genetic variations that play a protective role in the development of radiation-induced heart dysfunction (RIHD)
Summary
Over 17 million cases of cancer were diagnosed worldwide in 2018, and roughly 9.5 million cancer deaths were reported [1]. In national breast multicenter cancer patients, has been and other single institution reviews have shown a correlation between early death and radiation dose estimated that there is an approximately 4–16% relative increase in heart disease and/or major to the heart [12,14,19,20,21,22]. RT’s effectiveness in treating tumors in patients with mediastinal lymphomas, NSCLC trial and other singlelung, institution reviews have thymomas, and breast, or esophageal cancers [7].shown a correlation between early death and there is a need for understanding the mechanisms by whichseverely radiation causes cardiovascular radiation doseThus, to the heart [12,14,19,20,21,22]. Modern thoracic RT techniques aim to shield the heart and other
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