Abstract
Radiotherapy (RT) is a crucial treatment modality in managing cancer patients. However, irradiation dose sprinkling to tumor-adjacent normal tissues is unavoidable, generating treatment toxicities, such as radiation-associated cardiovascular dysfunction (RACVD), particularly for those patients with combined therapies or pre-existing adverse features/comorbidities. Radiation oncologists implement several efforts to decrease heart dose for reducing the risk of RACVD. Even applying the deep-inspiration breath-hold (DIBH) technique, the risk of RACVD is though reduced but still substantial. Besides, available clinical methods are limited for early detecting and managing RACVD. The present study reviewed emerging challenges of RACVD in modern radiation oncology, in terms of clinical practice, bench investigation, and multidisciplinary care. Several molecules are potential for serving as biomarkers and therapeutic targets. Of these, miRNAs, endogenous small non-coding RNAs that function in regulating gene expression, are of particular interest because low-dose irradiation, i.e., 200 mGy (one-tenth of conventional RT daily dose) induces early changes of pro-RACVD miRNA expression. Moreover, several miRNAs, e.g., miR-15b and miR21, involve in the development of RACVD, further demonstrating the potential bio-application in RACVD. Remarkably, many RACVDs are late RT sequelae, characterizing highly irreversible and progressively worse. Thus, multidisciplinary care from oncologists and cardiologists is crucial. Combined managements with commodities control (such as hypertension, hypercholesterolemia, and diabetes), smoking cessation, and close monitoring are recommended. Some agents show abilities for preventing and managing RACVD, such as statins and angiotensin-converting enzyme inhibitors (ACEIs); however, their real roles should be confirmed by further prospective trials.
Highlights
Radiotherapy (RT) is an essential treatment modality in managing cancer patients [1, 2]
Combined treatments irreversibly enhance the risk of RTCVD. ***Statin used in irradiated cancer patients with hypercholesterolemia may demonstrate double benefits of decreasing the blood level of cholesterol and the risk of radiation-associated cardiovascular dysfunction (RACVD). ****angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor antagonists used in irradiated patients with hypertension may have double benefits of controlling blood pressure and decreasing the risk of RACVD
MiR-30, miR-155, and miR-210 involve in the process of vascular calcification, which is one of the end events of RACVD that induces coronary artery stenosis and ischemic heart disease, via exosome delivery to vascular smooth muscle cells
Summary
Radiotherapy (RT) is an essential treatment modality in managing cancer patients [1, 2]. Clinical Challenges of Decreasing the Risk of RACVD in Modern Radiation Oncology Clinically, the overall incidence of RACVDs is rare but substantially encountered in irradiated patients with mediastinum lymphoma [8, 44, 66], head and neck [10, 45], esophagus [63], lung [13, 61, 62], and breast [12, 21, 56, 64] cancers.
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