Role of radiotherapy in the management of hepatocellular carcinoma: A systematic review

Abstract

Many patients with hepatocellular carcinoma (HCC) present with advanced disease, not amenable to curative therapies such as surgery, transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization (TACE) and radiation therapy. Especially TACE, delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy, has given favorable results on local control and survival. Radiotherapy, as a therapeutic modality of internal radiation therapy with radioisotopes, has also achieved efficacious tumor control in advanced disease. On the contrary, the role of external beam radiotherapy for HCC has been limited in the past, due to the low tolerance of surrounding normal liver parenchyma. However, technological innovations in the field of radiotherapy treatment planning and delivery, have provided the means of delivering radical doses to the tumor, while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy, evaluated for efficacy and safety for HCC, report encouraging results. In this review, we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment.

Pathology and images of radiation-induced hepatitis: a review article

“…The comprehensive term RILD includes conditions such as the different degrees of liver damage after veno-occlusive changes caused by whole or partial liver irradiation, although diagnostic criteria vary [2,3]. Recent reports propose the separation of RILD into "classical" and "nonclassical" forms (Table 1) [4,7,8].…”

“…In the subacute phase, obstruction of sublobular veins is superimposed upon the acutephase findings. In the chronic phase, moderate elastosis in the walls of the central veins and mild elastosis in the walls of perivenular sinusoids cause occlusion of the central veins because of fibrosis, lobular collapse and distortion, and accumulation of Kupffer cells, occasionally with deposition of hemosiderin [2,3,5,6].…”

“…Radiation that damages the subendothelial basement membrane leads to activation and aggregation of platelets and stimulates dormant hepatic stellate cells [3,4]. Damage to the hepatic venule endothelium contributes to the formation of microthrombi that cause venous obstruction, panlobular congestion, hepatocyte loss, and fibrosis mediated by transforming growth factor-β1 (TGF-β1) [15][16][17][18].…”

“…Radiation-induced hepatitis is described as "radiation hepatitis", "radiation-induced hepatic toxicity", "radiation-induced liver damage", and "radiation-induced liver disease (RILD)". RILD, which describes clinical and pathological features [1][2][3][4], refers to the severity of liver toxicity after high-dose radiotherapy delivered to large liver volumes or when the whole-liver tolerance dose (30)(31)(32)(33)(34)(35) is exceeded during external beam radiotherapy (RT).…”

Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through activation of JAK2/STAT3 signaling

“…The majority of patients with HCC are diagnosed at an advanced disease stage and are not amenable to potentially curative therapies, including surgery, transplantation, and radiofrequency ablation (3). Several therapies, including transarterial chemoembolization and radiation therapy are currently available for patients with locally advanced HCC (4). With recent advances in radiotherapy technology, a substantial dose of radiation can be precisely delivered to tumors, thereby reducing adverse effects on the surrounding normal tissues.…”