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Radiation therapy-associated toxicity: Etiology, management, and prevention.

Literature Information

DOI	10.3322/caac.21689
PMID	34255347
Journal	CA: a cancer journal for clinicians
Impact Factor	232.4
JCR Quartile	Q1
Publication Year	2021
Times Cited	176
Keywords	quality of life, radiation, side effects, toxicity
Literature Type	Journal Article, Review
ISSN	0007-9235
Pages	437-454
Issue	71(5)
Authors	Kyle Wang, Joel E Tepper

TL;DR

This article reviews the clinical implications of radiation therapy (RT) side effects across various organ systems, emphasizing that while RT is essential for cancer treatment, it can cause significant toxicity to normal tissues due to DNA damage. The findings highlight the importance of understanding these effects and the evolution of guidelines to minimize toxicity, which is crucial for improving patient outcomes in oncology.

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quality of life · radiation · side effects · toxicity

Abstract

Radiation therapy (RT) is a curative treatment for many malignancies and provides effective palliation in patients with tumor-related symptoms. However, the biophysical effects of RT are not specific to tumor cells and may produce toxicity due to exposure of surrounding organs and tissues. In this article, the authors review the clinical context, pathophysiology, risk factors, presentation, and management of RT side effects in each human organ system. Ionizing radiation works by producing DNA damage leading to tumor death, but effects on normal tissue may result in acute and/or late toxicity. The manifestation of toxicity depends on both cellular characteristics and affected organs' anatomy and physiology. There is usually a direct relationship between the radiation dose and volume to normal tissues and the risk of toxicity, which has led to guidelines and recommended dose limits for most tissues. Side effects are multifactorial, with contributions from baseline patient characteristics and other oncologic treatments. Technological advances in recent decades have decreased RT toxicity by dramatically improving the ability to deliver RT that maximizes tumor dose and minimizes organ dose. Thus the study of RT-associated toxicity is a complex, core component of radiation oncology training that continues to evolve alongside advances in cancer management. Because RT is used in up to one-half of all patients with cancer, an understanding of its acute and late effects in different organ systems is clinically pertinent to both oncologists and nononcologists.

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Primary Questions Addressed

1. What are the specific pathophysiological mechanisms underlying radiation therapy-associated toxicity in different organ systems?
2. How do patient-specific factors, such as age and comorbidities, influence the risk and severity of radiation therapy side effects?
3. What advancements in radiation delivery techniques have been most effective in reducing toxicity while maintaining tumor control?
4. How do the acute and late effects of radiation therapy differ in terms of management strategies for patients?
5. What role do multidisciplinary approaches play in the prevention and management of radiation therapy-associated toxicity?

Key Findings

1. Research Background and Objective

Radiation therapy (RT) is widely recognized as a curative treatment for various malignancies and plays a crucial role in alleviating tumor-related symptoms in patients. Despite its effectiveness, RT is associated with significant toxicity due to the non-specific biophysical effects of ionizing radiation, which can adversely affect surrounding healthy tissues and organs. This study aims to provide a comprehensive review of the etiology, clinical presentation, risk factors, and management strategies for RT-associated toxicity across different organ systems, thereby enhancing the understanding of both acute and late radiation effects.

2. Major Methods and Findings

The authors conducted a thorough review of existing literature on RT-related toxicity, focusing on the pathophysiology underlying the adverse effects on normal tissues. They explored how ionizing radiation induces DNA damage that not only targets tumor cells but also impacts the surrounding healthy tissue, leading to a spectrum of side effects. The study highlights that the severity and type of toxicity are influenced by cellular characteristics and the anatomical and physiological context of the affected organs. Notably, there is a direct correlation between the radiation dose and the volume of normal tissues irradiated, which informs clinical guidelines and recommended dose limits for various tissues. Advances in RT technology have been instrumental in minimizing these toxic effects by improving the precision of radiation delivery, thus maximizing tumor dose while protecting healthy tissue.

3. Core Conclusions

The study concludes that RT-associated toxicity is a complex phenomenon influenced by multiple factors, including patient-specific characteristics and concurrent oncological treatments. Understanding the acute and long-term effects of RT on different organ systems is essential for effective patient management. The findings underscore the importance of continuing education in radiation oncology to adapt to ongoing advancements in cancer treatment and to mitigate the risks associated with RT.

4. Research Significance and Impact

This research highlights the critical need for oncologists and allied health professionals to be well-versed in the intricacies of RT-associated toxicity. Given that RT is utilized in nearly half of all cancer patients, the insights provided in this review are clinically relevant and can guide practitioners in making informed decisions regarding treatment planning and patient care. Furthermore, the study emphasizes the ongoing evolution of radiation oncology practices in response to technological advancements, which not only enhance treatment efficacy but also prioritize patient safety by reducing the incidence of radiation-related adverse effects. As the field progresses, continued research into RT toxicity will be vital for improving patient outcomes and quality of life in cancer care.

Literatures Citing This Work

1. In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach. - Athanasia Pavlopoulou;Seyedehsadaf Asfa;Evangelos Gioukakis;Ifigeneia V Mavragani;Zacharenia Nikitaki;Işıl Takan;Jean-Pierre Pouget;Lynn Harrison;Alexandros G Georgakilas - Molecules (Basel, Switzerland) (2021)
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3. Flourish of Proton and Carbon Ion Radiotherapy in China. - Yue Li;Xiaoman Li;Jiancheng Yang;Sicheng Wang;Meitang Tang;Jiawen Xia;Yunzhe Gao - Frontiers in oncology (2022)
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9. Radiation-induced osteoradionecrosis of the ribs in a patient with breast cancer: A case report. - Suhong Kim;Young Seon Kim - Radiology case reports (2022)
10. Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments. - Yuanyun Wei;Yaqi Gong;Shuang Wei;Yonglin Chen;Jian Cui;Xiang Lin;Yueqiu Yu;Hongxia Yan;Hui Qin;Lan Yi - Archives of pharmacal research (2022)

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