Emerging Challenges of Radiation-Associated Cardiovascular Dysfunction (RACVD) in Modern Radiation Oncology: Clinical Practice, Bench Investigation, and Multidisciplinary Care

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.

Radioprotective countermeasures for radiation injury (Review)

“…Statins are used to lower lipid levels ( 57 ), and can ameliorate IR-induced inflammation and fibrotic remodeling ( 16 , 58 ). Statins have been found to reverse radiation-induced gene expression disorders such as p53.…”

Pathomechanisms and therapeutic opportunities in radiation-induced heart disease: from bench to bedside

“…Cancer patients presenting with clinical HF or IHD during or following cancer treatment need access to medical therapy with standard HF regimens or sometimes transcatheter or open surgical interventions [ 13 ]. Combined management with the control of age-related comorbidities and cardiovascular risk factors (such as hypertension, hypercholesterolemia, and diabetes) is crucial [ 135 ].…”

Breast Radiotherapy-Related Cardiotoxicity. When, How, Why. Risk Prevention and Control Strategies

“…As previously described, preclinical and clinical studies have identified different manifestations of RIHD in BC. However, in-depth knowledge of the biological mechanisms involved in RIHD is needed [ 113 ] to develop new non-invasive detection methods for diagnosis and follow-up. We need to identify specific biomarkers of RT-induced injury [ 64 ], to implement high-resolution imaging techniques in daily practice [ 114 , 115 , 116 ], and to combine the use of omics data with molecular imaging (single-photon emission computed tomography (SPECT-CT)) or positron emission tomography (PET-CT) for early RHID diagnosis [ 117 , 118 ].…”