Combination treatment of trans-catheter arterial chemoembolization (TACE) and conformal radiation therapy (RT) reported promising results in patients with hepatocellular carcinoma (HCC), but, optimal interval was not determined. We hypothesized that a two-week interval between TACE and RT would be optimal. Therefore, we designed this study to evaluate the safety and efficacy of scheduled interval TACE followed by RT. HCC patients who were not eligible for standard therapies were enrolled for scheduled interval TACE followed by RT (START). Patients received TACE on the first day of treatment, and then RT was delivered after 14 days. The entire course of treatment took between four and five weeks. In 81 patients (96.4%), START was completed in the planned treatment period. RT was delayed in the remaining three patients because of decreased liver function or poor performance status after TACE. Of the 81 patients, objective response was observed in 57 patients (70.4%). One unexpected death occurred after START due to hepatic failure. Other toxicities were manageable. The median survival was 14.7 months. There was a significant difference in overall survival according to the response to START (P < 0.001). In conclusion, START is safe and feasible.
Adult ; Carcinoma, Hepatocellular/mortality/radiotherapy/*therapy ; Combined Modality Therapy ; *Embolization, Therapeutic ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/mortality/radiotherapy/*therapy ; Male ; Middle Aged ; Prognosis ; Severity of Illness Index

OBJECTIVETo observe the long-term effects of combined transcatheter arterial chemoembolization (TACE) and radiotherapy for patients with large hepatocellular carcinoma (HCC) and to analyze the prognostic factors.

METHODSA total of 107 patients with large unresectable HCC (the largest diameter of tumor ranged from 5 to 18 cm) were treated with TACE followed by external-beam irradiation. Acute effects and survival rates were observed. The Cox proportional hazards model was used to analyze the prognostic factors.

RESULTSAn objective response was achieved in 48.6% of the cases. The cumulative survival rates at 1, 3, and 5 years were 59.4%, 28.4%, and 15.8%, respectively. The tumor number and irradiation dose were the independent prognostic factors. The cumulative survival rates of the patients with a solitary lesion (75.8%, 43.9%, and 26.8% at 1, 3, and 5 years, respectively) were significantly higher than those with multiple lesions (31.3%, and 5.0% at 1 and 3 years, respectively, P=0.0005). The survival rates of the patients received irradiation above 40 Gy (95.8%, 74.7%, and 37.4% at 1, 3, and 5 years, respectively) were significantly higher than those received 20~40 Gy (60.9%, 20.7%, and 10.3%, respectively) and those received radiation lower than 20 Gy (26.7%, 7.1%, and 7.1%, respectively, P=0.0001).

CONCLUSIONSCombined TACE with radiotherapy is a promising treatment for large unresectable HCC. The number of tumor is the most important clinical prognostic factor. Delivering the highest irradiation dose within the tolerance of the liver is the key to improve the long-term effect.

Adult ; Aged ; Carcinoma, Hepatocellular ; diagnosis ; mortality ; radiotherapy ; therapy ; Embolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; diagnosis ; mortality ; radiotherapy ; therapy ; Male ; Middle Aged ; Prognosis ; Survival Rate

BACKGROUND AND AIMS: We investigated the five-year survival outcomes of a large cohort of hepatocellular carcinoma (HCC) patients who were treated at a single institute, and this is a follow-up study of a previous report. METHODS: Nine hundred four HCC patients who were treated at the National Cancer Center Korea were enrolled and they were followed till February 2007. RESULTS: The mean age of the patients was 56.0 years and 731 patients were male. Six hundred seventy-seven (74.9%) patients died and the overall 5-year survival rate (5-YSR) was 23.9%. The 5-YSRs of the patients with modified UICC stage I, II and III were 61.2%, 54.4% and 18.4%, respectively, and the median survival time was 4.3 and 3.7 months for the stage IVa and IVb patients, respectively. For the analysis of the treatment modality, surgical resection showed significantly better outcomes for the five-year survival as compared with transcatheter arterial chemoembolization (TACE) for Child-Pugh A patients with modified UICC stage I or II disease (80.1% vs 52.8%, respectively, P<.001), or stage III disease (60.7% vs 17.0%, respectively, P<.001). For patients with advanced stage IVb disease, TACE, systemic chemotherapy and radiotherapy increased the median survival period more than conservative management for the Child-Pugh class A patients. The serum alpha-fetoprotein level, portal vein tumor thrombosis, the Child-Pugh class, the tumor stage, the tumor type and symptoms were related to the prognosis. CONCLUSIONS: This study presented, for the first time, the 5-YSRs of a cohort of HCC patients.
Aged ; Carcinoma, Hepatocellular/etiology/*mortality/surgery ; Chemoembolization, Therapeutic ; Cohort Studies ; Combined Modality Therapy ; Female ; Humans ; Korea ; Liver Neoplasms/etiology/*mortality/surgery ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Radiotherapy, Conformal ; Severity of Illness Index ; Survival Rate

PURPOSE: For locally unresectable hepatocellular carcinoma (HCC) patients, concurrent chemoradiotherapy (CCRT) has been applied as a loco-regional treatment. After shrinkage of tumors in selected patients, surgical resection is performed. The aim of this study was to evaluate prognostic factors and long-term survivors in such patients. MATERIALS AND METHODS: From January 2000 to January 2009, 264 patients with HCC were treated with CCRT (45 Gy with fractional dose of 1.8 Gy), and intra-arterial chemotherapy was administered during radiotherapy. Eighteen of these patients (6.8%) underwent hepatic resection after showing a response to CCRT. Cases were considered resectable when tumor-free margins and sufficient remnant volumes were obtained without extrahepatic metastasis. Prior to operation, there were six patients with complete remission, 11 with partial remission, and six with stable disease according to modified Response Evaluation Criteria in Solid Tumors. RESULTS: In pathologic review, four patients (22.2%) showed total necrosis and seven patients (38.9%) showed 70-99% necrosis. A high level of necrosis (> or =80%) was correlated with low risk for extrahepatic metastasis and long-term survival. In univariate analyses, vessel invasion and capsular infiltration were significantly correlated with disease free survival (DFS) (p=0.017 and 0.013, respectively), and vessel invasion was significantly correlated with overall survival (OS) (p=0.013). In multivariate analyses, capsule infiltration was a significant factor for DFS (p=0.016) and vessel invasion was significant for OS (p=0.015). CONCLUSION: CCRT showed favorable responses and locally advanced HCC converted into resectable tumor after CCRT in selected patients. Long-term survivors showed the pathological features of near total necrosis, as well as negative capsule and vessel invasion.
Adult ; Aged ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; Chemoradiotherapy/*methods ; Cisplatin/administration & dosage ; Disease-Free Survival ; Female ; Fluorouracil/administration & dosage ; Humans ; Liver Neoplasms/mortality/pathology/*therapy ; Male ; Middle Aged ; Prognosis ; Radiotherapy, Conformal ; Remission Induction ; Republic of Korea/epidemiology ; *Salvage Therapy ; Survival Rate ; Treatment Outcome ; Tumor Burden