Abstract
Radiotherapy remains a mainstay of cancer treatment, being used in roughly 50% of patients. The precision with which the radiation dose can be delivered is rapidly improving. This precision allows the more accurate targeting of radiation dose to the tumor and reduces the amount of surrounding normal tissue exposed. Although this often reduces the unwanted side effects of radiotherapy, we still need to further improve patients’ quality of life and to escalate radiation doses to tumors when necessary. High‐precision radiotherapy forces one to choose which organ or functional organ substructures should be spared. To be able to make such choices, we urgently need to better understand the molecular and physiological mechanisms of normal tissue responses to radiotherapy. Currently, oversimplified approaches using constraints on mean doses, and irradiated volumes of normal tissues are used to plan treatments with minimized risk of radiation side effects. In this review, we discuss the responses of three different normal tissues to radiotherapy: the salivary glands, cardiopulmonary system, and brain. We show that although they may share very similar local cellular processes, they respond very differently through organ‐specific, nonlocal mechanisms. We also discuss how a better knowledge of these mechanisms can be used to treat or to prevent the effects of radiotherapy on normal tissue and to optimize radiotherapy delivery.
Highlights
The number of new cancer cases per year is estimated to rise to 22.2 million by the year 2030 worldwide [1], and about 12 million patients will receive radiotherapy as part of their treatment [2,3]
The increasing availability of high-precision radiotherapy is changing the way that we look at its effects on normal tissue
Changes to dose distribution and our increasing knowledge of the local and nonlocal effects of radiotherapy on normal tissue warrant the use of a different approach to prevent and/or to treat these effects
Summary
The number of new cancer cases per year is estimated to rise to 22.2 million by the year 2030 worldwide [1], and about 12 million patients will receive radiotherapy as part of their treatment [2,3]. Radiotherapy is well tolerated by most patients, some experience radiation-induced side effects, the severity and frequency of which can be reduced by modern, more precise therapies, such as particle therapy and advanced image-guided technologies This improved precision can be used to minimize the radiation dose to normal tissue thereby reducing side effects, but can be used for escalation of dose to poorly responding tumors without increasing the risk of side effects. Oversimplified approaches using constraints on mean doses and irradiated volumes of normal tissues receiving a specified dose are used to plan treatments with minimized risk of radiation side effects Consensus publications such as the Emami paper were the main sources for constraints [4]. Modern radiotherapy technologies offer greater precision but their optimal use requires radiation oncologists to have a better understanding of how these therapies affect normal tissue
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