Abstract
Simple SummarySide effects caused by the concomitant irradiation of normal tissue during radiotherapy for cancer treatment can negatively affect the patient’s quality of life and limit the radiation dose that can safely be administered to the tumor. Recently, considerable developments have been achieved in radiotherapy and imaging technologies, allowing the selective sparing of the regions within organs that contribute most to the development of these side effects. This review discusses regional variation in the response to radiation in several organs, including the brain, salivary glands, cardiopulmonary system, pancreas, and bladder. Regional responses are shown to originate from general principles, such as the localization of target cells or function. We conclude that regional responses are a general phenomenon that should be studied in other organs. This will facilitate further optimization of the use of modern radiotherapy technologies.Normal tissue side effects remain a major concern in radiotherapy. The improved precision of radiation dose delivery of recent technological developments in radiotherapy has the potential to reduce the radiation dose to organ regions that contribute the most to the development of side effects. This review discusses the contribution of regional variation in radiation responses in several organs. In the brain, various regions were found to contribute to radiation-induced neurocognitive dysfunction. In the parotid gland, the region containing the major ducts was found to be critical in hyposalivation. The heart and lung were each found to exhibit regional responses while also mutually affecting each other’s response to radiation. Sub-structures critical for the development of side effects were identified in the pancreas and bladder. The presence of these regional responses is based on a non-uniform distribution of target cells or sub-structures critical for organ function. These characteristics are common to most organs in the body and we therefore hypothesize that regional responses in radiation-induced normal tissue damage may be a shared occurrence. Further investigations will offer new opportunities to reduce normal tissue side effects of radiotherapy using modern and high-precision technologies.
Highlights
IntroductionExamples range from dry mouth, hormonal dysfunction, neurocognitive impairment, gastro-intestinal problems, metabolic disorders, cardiac failure, and infertility, to secondary cancers [2,7]
Dose-dependent cortical thinning was found to occur in regions of the frontal, parietal, and temporal lobes, which are involved in higher-order cognitive functions, such as memory, attention, and executive function [50,51]
The optic nerve—which is the structure connecting the retina to the brain, and the optic chiasm—the region of the brain where the optic nerves cross, which is important for the transmission of the visual information from the optic nerve to the occipital lobe of the brain—are both seen as organs at risk in brain and head and neck tumors [11]
Summary
Examples range from dry mouth, hormonal dysfunction, neurocognitive impairment, gastro-intestinal problems, metabolic disorders, cardiac failure, and infertility, to secondary cancers [2,7] These late responses are generally more complex; they include multiple cell types and biological pathways involved in processes such as inflammation, fibrogenesis, and vascular damage [7]. The identification of regional responses can improve the understanding of mechanisms leading to late side effects This will allow the optimal use of the increased precision offered by modern radiotherapy technologies by using region- and substructurebased objectives for radiotherapy treatment planning to achieve better sparing of identified critical regions and structures. We discuss regional variation in radiation-induced normal tissue damage in several organs, addressing whether they play a significant role in their functional response. We discuss if these regional responses are rare or if their occurrence in organs can be considered a general phenomenon
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