Clinical results and prognostic factors in radiotherapy for unresectable hepatocellular carcinoma: a retrospective study of 158 patients

Abstract

Purpose: To analyze the treatment results and prognostic factors affecting survival in patients with unresectable hepatocellular carcinoma treated with local radiotherapy (RT).

Methods and Materials: Between 1992 and 2000, 158 patients with unresectable hepatocellular carcinoma received local RT. Sixty-seven patients had an advanced UICC Stage III lesion and 91 patients had Stage IVA. The mean tumor size was 9.0 ± 3.0 cm, and liver cirrhosis was present in 142 patients. Local RT was combined with transarterial chemoembolization as primary treatment (107 patients) or as salvage after failure of repeated transarterial chemoembolization (51 patients). The mean radiation dose was 48.2 ± 7.9 Gy in daily 1.8-Gy fractions.

Results: The mean follow-up was 21.6 months after diagnosis and 14.6 months after RT. The response rate was 67.1%. The overall survival rate at 2 and 5 years was 30.5% and 9%, respectively, from the time of diagnosis (median survival time 16 months) and 19.9% and 4.7%, respectively, after RT (median survival time 10 months). On univariate analysis, tumor size (p = 0.047), the presence of portal vein thrombosis (p = 0.007), and RT dose (p = 0.001) were significant factors for survival. However, on multivariate analysis, RT dose was the only significant factor (p = 0.01).

Conclusion: Local RT achieved substantial tumor regression and survival. The radiation dose was found to be a significant prognostic factor in the RT of hepatocellular carcinoma. Additional efforts for dose escalation are warranted to improve the treatment results in parallel with better protecting the nontumorous liver.

Introduction

Primary hepatocellular carcinoma (HCC) is a major malignant disease in parts of Africa and Asia (1). The best prognosis can be achieved through curative surgical resection of early disease, which is possible practically, given the recent progress in imaging technique capabilities. However, the number of resected cases is still limited, even for small tumors because of the unique characteristics of this tumor, including multifocality, early vascular invasion, and concurrent liver cirrhosis 2, 3.

Various forms of therapy have been tried for unresectable HCC. Systemic chemotherapy did not prove effective (4). Intrahepatic chemotherapy produced a better response rate; however, the placement of an infusion device is often associated with significant complications 5, 6. Percutaneous ethanol injection therapy has been found effective, but its indications are limited (7). Transcatheter arterial chemoembolization (TACE) has achieved improved survival; however, the antitumor effect of TACE alone has frequently been incomplete, even after repeated treatments (8).

Radiotherapy (RT) for the treatment of HCC has been attempted for more than 4 decades. Early trials adopted whole liver irradiation but used an inadequate radiation dose 9, 10, 11. Because of the unsatisfactory results obtained with this low-dose whole liver irradiation, RT has not long been considered for the treatment of HCC. Recently, local, not whole, liver RT has been attempted by several investigators, who have shown that high doses of radiation can be safely delivered to a portion of the liver alone or in combination with other nonsurgical modalities 12, 13, 14, 15, 16, 17. Their results suggest that local RT can be an effective component of the treatment regimen for HCC. Although the role of RT in the management of HCC has been increasingly recognized, several questions remain to be answered. One of these involves the identification of prognostic factors to better understand and improve the outcome of HCC after RT.

In our institution, external beam RT (EBRT) has been actively applied for the treatment of HCC since the early 1990s 15, 16, and RT has been used alone or in combination with other treatment modalities such as TACE. The treatment has been applied either at the time of diagnosis or when repeated TACE has failed and salvage treatment is required. In this retrospective study, we analyzed the treatment results and prognostic factors affecting survival in 158 HCC patients treated with RT.