Challenge and hope in radiotherapy of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most critical global health issues. With frequent association of viral liver disease, HCC is highly complex, harboring both cancer and chronic liver disease. The tumor stage and underlying liver function are both major determinants of the treatment selection as well as prognosis in HCC patients, thus allowing no more than a 20% chance for potentially curative therapies. Radiotherapy technology has been evolved remarkably during the past decade, and radiation can be precisely delivered, thereby permitting higher doses to the tumour and reduced doses to surrounding normal tissues. There has been increasing interest in the merits of radiotherapy in HCC over the past few years, as indicated by a Pub Med search. Radiotherapy has been used as the definitive therapy with curative intent in early stage tumours. It has been used also in combination with TACE for intermediate stage tumours. In locally advanced tumours, radiotherapy has been combined with systemic agents. Despite its efficacy, radiotherapy has not yet been incorporated into the standard management guidelines of HCC. The lack of high evidence level data, especially randomized controlled trials, has posed an obstacle in including radiotherapy into the routine treatment schema of HCC. Therefore, well-designed prospective studies are strongly recommended using developing technology for radiotherapy alone or combination therapies. Also, many issues such as the optimal dose-fractionation, intra- or extrahepatic metastasis after radiotherapy, and radiation-induced hepatic dysfunction remain to be solved. In this review, current status of radiotherapy for HCC will be discussed with regard to technical consideration and combination strategy. The limitation and future perspectives will also be discussed.

Keywords: Radiotherapy; hepatocellular carcinoma.

Fig. 1

Number of publications on radiotherapy for liver cancer, shown through PubMed search.

Fig. 2

Illustration of an exemplary patient treated with TACE plus radiotherapy (54 Gy) for locally advanced HCC. CT scan images are shown for preTACE (A), postTACE (B), postradiotherapy (C), and postresection (D). Note tumor regression as well as compensating hypertrophy of uninvolved liver. No tumor cells were found in surgical specimen. HCC, Hepatocellular carcinoma; TACE, transarterial chemoembolization.

Fig. 3

Illustration of an exemplary patient treated with concurrent radiotherapy (45 Gy) and intraarterial chemotherapy for locally advanced HCC accompanied with portal vein tumor thrombosis. CT scan images of pretreatment (A) and posttreatment (B) are shown. Tumor regression in the primary and portal vein is noted, followed by curative surgical resection (C). HCC, Hepatocellular carcinoma.

Fig. 4

Survival outcome after treatment with either TACE alone (broken line) or TACE plus radiotherapy (solid line) for similar clinical group of HCC patients. The 2 year survival rate appears higher in TACE plus radiotherapy group (36% vs. 14%, p < 0.05, Log-rank test). TACE, transarterial chemoembolization; TACE + RT, transarterial chemoembolization radiotherapy; HCC, Hepatocellular carcinoma.

Fig. 5

Survival outcome after concurrent radiotherapy and intraarterial chemotherapy for HCC patients with portal vein tumor thrombosis. Note median survival time of 16.7 months and 2 yr survival rate of 33.7%. HCC, Hepatocellular carcinoma.

Fig. 6

Various dose fractionations in current practice, shown in a national retrospective cohort study. Radiation dose calculated in biologically effective dose (BED) was shown as a significant factor for survival.