## 2 RT-Induced Toxicities and Their Clinical Management  
Radiosensitivity reactions range from inflammation and fibrosis to radiation hypersensitivity syndromes (e.g., ataxia-telangiectasia, Fanconi anemia, radiosensitive severe combined immunodeficiency disease, etc). The effects can be either acute, including erythema, diarrhea, dermatitis, and cystitis, or late, entailing vascular damage, atrophy, infertility, and fibrosis [14]. Currently, the management of adverse reactions follows consensus guidelines that help healthcare professionals provide care to oncology patients before, during, and after cancer treatment with respect to their cardiovascular health status. The earliest criteria defining radiation toxicity following RT in the clinic are traced to almost five decades ago. In the 1970s, the Radiation Therapy Oncology Group (RTOG) established radiotoxicity criteria, focusing primarily on acute toxicities such as skin reactions, gastrointestinal symptoms, and hematologic alterations. These criteria set the basic framework for evaluating the severity of adverse radiologic effects by providing a grading scale ranging from 0 to 5, where 0 indicates no toxicity and 5 represents severe toxicity. In the 1980s, the RTOG toxicity criteria were updated, incorporating additional organs and systems, and refining the grading scales to provide more precise assessments. Subsequent updates in the 1990s expanded the criteria to include chronic radiation toxicities, also considering long-term effects. In 1995, RTOG collaborated with the European Organization for Research and Treatment of Cancer (EORTC) to develop a joint set of radiotoxicity criteria, known as the RTOG/EORTC criteria [15]. This collaboration aimed to standardize the assessment and reporting of radiation toxicities to ensure consistency in clinical trials and research studies. Over time, advancements in the knowledge and understanding of the mechanisms underlying radiation toxicities led to the development of more comprehensive and sophisticated radiotoxicity criteria, such as the Common Terminology Criteria for Adverse Events (CTCAE) initiated by the National Cancer Institute (NCI) [16], that provide a widely accepted framework for grading and reporting treatment-related toxicities, covering a comprehensive range of organs and systems, with toxicity grades from 1 to 5 according to severity. The criteria include skin reactions, mucositis, gastrointestinal complications, and hematologic and neurologic disturbances. These newest criteria reflect the most up-to-date understanding of radiation toxicities and are widely used in clinical practice and research settings to assess and manage the adverse effects of RT. In a recent review regarding skin toxicity following RT for breast cancer patients, [PERSON] et al., 2022 highlighted skin thickening, less echogenic dermis, a poorly visible dermis-subcutaneous fat boundaryand decreased Pearson correlation coefficient of the hypodermis compared with the nonirradiated skin [17]. Mucositis affects the mucous membranes, causing pain, ulceration, and difficulty in swallowing. In a systematic review, [PERSON] et al., 2003 displayed the elevated rates of mucositis in RT-treated patients with head and neck cancer, a severe form of radiotoxicity that may lead to hospitalization and treatment interruptions [18]. Fatigue is a frequent side effect associated with physical and cognitive impairment. Radiation-induced fibrosis involves the progressive scarring of irradiated tissues, leading to functional impairment. The severity and occurrence of these toxicities depend on various factors such as radiation dose, fractionation scheme, and the irradiation field location. Proper management and supportive care are essential to mitigate these toxicities and improve the quality of life for cancer patients undergoing RT. A key concern during the administration of RT is to increase radiosensitization in cancer cells while protecting normal tissues.