Carcinoma, Hepatocellular ; radiotherapy ; therapy ; Combined Modality Therapy ; Humans ; Liver Neoplasms ; radiotherapy ; therapy ; Radiotherapy ; methods

Carcinoma, Hepatocellular ; diagnostic imaging ; radiotherapy ; therapy ; Humans ; Liver Neoplasms ; diagnostic imaging ; radiotherapy ; therapy ; Ultrasonography

Biological Therapy ; Carcinoma, Hepatocellular ; drug therapy ; radiotherapy ; therapy ; Humans ; Liver Neoplasms ; drug therapy ; radiotherapy ; therapy ; Radiography, Interventional ; Ultrasonic Therapy

The role of radiotherapy in practice is mainly palliative. According to the Practice Guidelines for Management of Hepatocellular Carcinoma (2009) developed by the Korean Liver Cancer Study Group and the National Cancer Center, Korea, radiotherapy can be applied for 1) refractoriness to trans-catheter hepatic arterial chemo-embolization, 2) portal vein tumor thrombosis, and 3) palliative therapy to reduce the symptoms caused by hepatocellular carcinoma. Radiotherapy is one of the most rapidly developing fields of medical research. Recent advances in intensity-modulated radiotherapy, image-guided radiotherapy, and respiratory-gated radiotherapy technologies have enabled more accurate and precise radiation delivery for the treatment of hepatocellular carcinoma. Proton therapy is also emerging as a candidate therapy for ablative measures for patients ineligible for other curative local therapies. Due to recent advances in radiotherapy technologies, radiotherapy for hepatocellular carcinoma has been evolving into stereotactic ablative radiotherapy, which delivers an ablative dose of radiation in 1 to 4 sessions. Clinical series have confirmed that it is safe in Child-Pugh A patients and local control is sustained. The possibility for performing phase 3 randomized clinical trials involving the radiotherapy modality has increased with those advances. Not merely palliative, the role of radiotherapy in the treatment of hepatocellular carcinoma will be expanded to potentially curative therapy in patients who are ineligible for other curative local therapies.
Carcinoma, Hepatocellular* ; Humans ; Korea ; Liver Neoplasms ; Palliative Care ; Portal Vein ; Proton Therapy ; Radiotherapy* ; Radiotherapy, Image-Guided ; Radiotherapy, Intensity-Modulated ; Thrombosis

Eighty-four patients with unresectable primary hepatocellular carcinoma due either to locally advanced lesion or to association with liver cirrhosis were treated with combined radiotherapy and hyperthermia from April 1988 to January 1991. Purpose of this study was to assess thermometry, response rate, toxicity, and survival in those patients. External radiotherapy was given with a total of 30.6 Gy/3.5 wks. Hyperthermia was given twice a week with a total of 6 treatment sessions using an 8 MHz radiofrequency capacitive type heating machine. Each hyperthermia session was started within 30 min following radiotherapy and continued for 30-60 min. Thermal data were analysed with maximum, minimum, and average temperatures of the tumors. Thermal mapping was also done. In thermometry results, maximum, minimum, and average temperatures of the tumors were 41.9 +/- 1.3 degrees C, 39.9 +/- 1.0 degrees C, and 40.8 +/- 0.9 degrees C, respectively. The fraction over 40 degrees C was 73 +/- 32% with a wide variation from 15% to 100%. Among 67 assessable patients, 27 patients showed tumor regression of more than 50% of the original tumor volume (40.3% response rate). Symptomatic improvement was observed in 78.6% of the patients. Acute toxicities during the treatment were mostly acceptable local pain (51.2%) and local fat necrosis (13.1%). The actuarial 1-year, 2-year, and 3-year survival rates were 44.8%, 19.7%, and 15.6%, respectively. Median survival was 6 months. In view of acceptable toxicities and the current rate of survival, further evaluation of combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma is warranted.
Carcinoma, Hepatocellular/radiotherapy/*therapy ; Combined Modality Therapy ; Female ; Human ; *Hyperthermia, Induced ; Liver Neoplasms/radiotherapy/*therapy ; Male ; Middle Age ; Remission Induction

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.
Carcinoma, Hepatocellular/drug therapy/radiography/*radiotherapy ; Humans ; Liver/radiation effects ; Liver Neoplasms/drug therapy/radiography/*radiotherapy ; Neoplasm Metastasis ; Radiation Dosage ; Radiotherapy, Adjuvant/adverse effects/methods ; Treatment Outcome

Animals ; Combined Modality Therapy ; Endostatins ; genetics ; Genetic Therapy ; Liver Neoplasms, Experimental ; radiotherapy ; therapy ; Mice ; Mice, Nude ; Neoplasm Transplantation

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

Four cases of hepatocellular carcinoma (HCC) were surgically resected following combined radiotherapy (RT) and hyperthermia (HT). Complete necrosis of the tumor without viable tumor cell was found in one case and extensive tumor necrosis was observed in the other three cases; the percentage of necrosis in the specimens were 40%, 70%, and 80%, respectively. Histologic assessment showed mainly coagulative necrosis in the tumor with focal liquefactive necrosis. Cystic dilatation of sinusoids was observed in both tumor and nontumorous normal liver tissue. Other changes in normal liver tissue were unremarkable except for infiltration of inflammatory cells, fatty change, and proliferation of the bile ducts which can usually be seen beyond the area where any space occupying lesions are present. It is concluded that combined radiotherapy and hyperthermia can significantly induce coagulative necrosis of hepatocellular carcinoma with nonsignificant minimal histologic changes in adjacent nontumorous liver tissue.
Carcinoma, Hepatocellular/*pathology/radiotherapy/surgery/*therapy ; Combined Modality Therapy ; Female ; Human ; *Hyperthermia, Induced ; *Liver Neoplasms/*pathology/radiotherapy/surgery/*therapy ; Male ; Middle Aged ; Necrosis

Several anticancer chemotherapeutic agents (5-fluorouracil, adriamycin and cisplatinum) and desferrioxamine, an iron chelator, were tested with regard to cytotoxicity and to the combined effect on radiation induced cell killing using two human hepatoma cell lines (HepG2 and PLC/PRF/5). Survival fractions were measured by quantitative colorimetric assay (MTT assay) and dose-response curves were plotted. MTT assay could be successfully used in the assessment of radiosensitivity in addition to chemosensitivity, because a good linear relationship between optical densities and cell numbers was observed and cells approached exponential growth for the first 7 days of culture when 5 x 10(3) or less cells were inoculated per well in our study. Steepness of the final slope (D0), width of the shoulder (D0) and the extrapolation number (n) of radiation survival curves were 1061.72 rad, 226.43 rad and 1.25 respectively in HepG2 and 1091.38 rad, 268.42 rad and 1.29 respectively in PLC/PRF/5. After combining anticancer chemotherapeutic agents and desferrioxamine with radiation, the widths of the shoulders were decreased whereas sensitizer enhancement ratios were increased as the concentration of drugs increased in both cell lines. These results suggest that neither anticancer chemotherapeutic agents nor desferrioxamine enhance cell killing induced by radiation alone, but suggested the possibility that they inhibit the repair of radiation damage.
Antineoplastic Agents/*pharmacology ; Carcinoma, Hepatocellular/*drug therapy/*radiotherapy ; Deferoxamine/*pharmacology ; Human ; Liver Neoplasms/*drug therapy/*radiotherapy ; Support, Non-U.S. Gov't ; Tumor Cells, Cultured/drug effects/radiation effects