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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 side effects of radiation therapy (RT), a common cancer treatment, highlighting the balance between effective tumor targeting and the risk of toxicity to surrounding healthy tissues. It emphasizes the importance of understanding these effects, which are influenced by radiation dose, patient characteristics, and technological advancements in RT delivery, underscoring the evolving nature of radiation oncology in improving patient outcomes.

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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 therapy technology have shown the most promise 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 undergoing treatment?
5. What role does multidisciplinary care play in addressing the complexities of radiation therapy-associated toxicity in cancer patients?

Key Findings

1. Research Background and Objectives

Radiation therapy (RT) is a cornerstone treatment modality for numerous malignancies, providing both curative and palliative care to patients. While effective in targeting tumor cells, RT can inadvertently damage surrounding healthy tissues, leading to various toxicities. This study aims to comprehensively review the etiology, management, and prevention of RT-associated toxicities across different organ systems. By understanding the pathophysiology and risk factors associated with RT side effects, the authors intend to enhance clinical practices and improve patient outcomes in oncology.

2. Main Methods and Findings

The authors conducted a thorough review of existing literature related to RT-associated toxicity, focusing on clinical contexts, pathophysiological mechanisms, and the presentation of side effects in various organ systems. They highlighted that ionizing radiation induces DNA damage, which is crucial for tumor cell death but also affects normal tissues, resulting in acute and late toxicities. The findings emphasize a direct correlation between the radiation dose, the volume of normal tissue exposed, and the risk of toxicity. Notably, the study identifies multiple factors contributing to side effects, including patient-specific characteristics and the influence of concurrent oncologic treatments. Furthermore, advancements in radiation technology have significantly reduced the incidence of toxicity by enabling more precise targeting of tumors while sparing healthy tissues.

3. Core Conclusions

The study concludes that understanding the acute and late effects of RT on various organ systems is essential for oncologists and allied health professionals. The authors stress that a multifactorial approach is necessary when evaluating RT-related toxicity, as it encompasses a complex interplay between treatment variables and patient-specific factors. Additionally, the evolution of radiation techniques and guidelines has been pivotal in minimizing adverse effects, thereby enhancing the therapeutic windows for cancer patients.

4. Research Significance and Impact

This research holds significant implications for the field of radiation oncology and cancer treatment paradigms. Given that approximately half of all cancer patients receive RT, insights into its toxicities are crucial for improving the quality of care. By providing a detailed examination of the mechanisms and management strategies for RT-associated side effects, the study serves as a vital resource for clinicians navigating the complexities of cancer therapy. Moreover, it underscores the necessity for ongoing research and training in radiation oncology to adapt to technological advancements and enhance patient safety, ultimately aiming for better therapeutic outcomes in cancer management.

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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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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