Strategies for prediction and mitigation of radiation-induced liver toxicity

Abstract

Although well described in the 1960s, liver toxicity secondary to radiation therapy, commonly known as radiation-induced liver disease (RILD), remains a major challenge. RILD encompasses two distinct clinical entities, a ‘classic’ form, composed of anicteric hepatomegaly, ascites and elevated alkaline phosphatase; and a ‘non-classic’ form, with liver transaminases elevated to more than five times the reference value, or worsening of liver metabolic function represented as an increase of 2 or more points in the Child–Pugh score classification. The risk of occurrence of RILD has historically limited the applicability of radiation for the treatment of liver malignancies. With the development of 3D conformal radiation therapy, which allowed for partial organ irradiation based on computed tomography treatment planning, there has been a resurgence of interest in the use of liver irradiation. Since then, a large body of evidence regarding the liver tolerance to conventionally fractionated radiation has been produced, but severe liver toxicities has continued to be reported. More recently, improvements in diagnostic imaging, radiation treatment planning technology and delivery systems have prompted the development of stereotactic body radiotherapy (SBRT), by which high doses of radiation can be delivered with high target accuracy and a steep dose gradient at the tumor – normal tissue interface, offering an opportunity of decreasing toxicity rates while improving tumor control. Here, we present an overview of the role SBRT has played in the management of liver tumors, addressing the challenges and opportunities to reduce the incidence of RILD, such as adaptive approaches and machine-learning–based predictive models.

The effect of chronic low-dose environmental radiation on organ mass of bank voles in the Chernobyl exclusion zone

“…The spleen is involved in the immune system responses, thus is known to have negative response to high level of contaminants (Miller et al 2005;Toesca et al 2018). There was a positive relationship between relative spleen mass and radiation.…”

“…Energetically costly organs such as the brain and liver were expected to show strong negative responses to radioactive contamination (Aiello and Wheeler 1995;Navarrete et al 2011). The liver and spleen are also involved in detoxification and the functioning immune system, thus these tissues are known to suffer from high level of exposures to contaminants (Miller et al 2005;Toesca et al 2018). Kidneys are responsible for filtration of blood and are, therefore, exposed to all watersoluble products, including Cs 137 , and thus were also expected to suffer consequences of elevated internal radiation exposure (Nelson et al 1961).…”

Stereotactic Ablative Radiotherapy Fractionation for Hepatocellular Carcinoma in the United States

“…Historically, the use of external beam radiation was limited by collateral damage to normal liver parenchyma. In recent years, the development of partial organ irradiation using 3D conformal radiation therapy led to increased interest in the use of EBRT in inoperable HCC cases [10]. More recently, SABR has led to further increased interest and application of EBRT due to its high target accuracy and steep dose gradient, which in turn allows for improvement in local control without increased risk of toxicity [11,12].…”

Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems

“…Radiation-induced liver disease is relatively rare and is generally associated as an unintended consequence of high-dose radiotherapy. Regardless, significant injuries to the liver can occur following these toxic insults and can have dire health consequences to the individuals [117]. The pathological hallmark of the radiationassociated liver disease in humans is hepatic veno-occlusive disease [118].…”