Untitled

Abstract

The purpose of this study was to evaluate treatment-related toxicity, outcome, patterns of failure, and prognostic factors for patients with stage III unresectable hepatocellular carcinoma (HCC) treated with a combination of local 3-dimensional conformal radiotherapy (3D-CRT) and transcatheter arterial chemoembolization (TACE) under the support of G-CSF. From October 1997 to August 2001, 45 patients with stage III unresectable hepatocellular carcinoma underwent transcatheter arterial chemoembolization with local 3D-CRT. Twenty-seven patients were classified as having stage IIIA disease according to the American Joint Committee on Cancer (AJCC) staging system and 18 were classified as stage IIIB. The mean diameter of the treated hepatic tumor was 8.5 cm. Before 3D-CRT, 2 cycles of transcatheter arterial chemoembolization were prescribed. Forty-eight hours later, the G-CSF was prescribed for 5 days after the completion of every TACE. With the interval of 10 to 14 days after the second cycle of TACE, 3D-CRT was prescribed to all patients with a total dose of 50.4 Gy at 1.8 Gy per fraction 5 days per week. After the completion of 3D-CRT, the additional 2 cycles of TACE were given. All patients were monitored for treatment-related toxicity, outcome, patterns of failure, causes of death, and prognostic factors. Forty-two of 45 patients were treated smoothly with the primary schedule. In a median follow-up period of 27 months, 22 patients were alive and 23 were dead. Progressive disease occurred in 28 patients, including local recurrence alone (4 patients), distant metastases with local recurrence (8 patients), and distant metastases alone (16 patients). Nine patients developed radiation-induced liver disease (RILD). Three patients had treatment-related gastrointestinal bleeding. There were 2 treatment-related deaths, including 1 from RILD and 1 from gastrointestinal bleeding. Complete regression (CR) was observed in 6 patients, partial regression (PR) in 35 patients, and stable disease (SD) in 4 patients. The median overall survival duration from treatment was 23.5 months with a 1-year overall survival rate of 68.5%, a 2-year survival rate of 48.3%, and a 3-year survival rate of 22.6%. The median freedom from progressive disease survival duration from treatment was 25 months with 1-year, 2-year, and 3-year progression-free survival rates of 76.2%, 56.8%, and 42.4%, respectively. The stage of HCC, regional lymph node status, portal vein thrombosis, pretreatment alpha-fetoprotein level (AFP), and tumor size affected the treatment outcomes significantly. Therefore, for patients with stage III unresectable hepatocellular carcinoma, combined local 3D conformal radiotherapy with transcatheter arterial chemoembolization under the support of G-CSF is an effective treatment protocol. Further research is required to decrease distant metastases and to determine the safe irradiation dose-volume.

Radiotherapeutic Strategies in the Management of Hepatocellular Carcinoma

“…A similar range of response rates with TACE followed by radiation therapy has been reported by other investigators as well [50,51,52,53]. Overall, following a variety of fractionations and doses in a variety of series, 1-year survival rates ranged from 50 to 95%, and 5-year survival rates ranged from 9 to 25% following 40–60 Gy delivered over 1–5 weeks [54,55,56,57,58]. Reasons for the large range of outcomes include substantial heterogeneity in patient selection, treatment intent, and treatment delivered.…”

Scheduled Interval Trans-Catheter Arterial Chemoembolization Followed by Radiation Therapy in Patients with Unresectable Hepatocellular Carcinoma

“…Based on the previous TACE plus RT studies, we hypothesized that a two-week interval between TACE and RT would be tolerable (20). Under this background, we conducted this trial using a two-week interval between TACE and RT (START) in patients with unresectable HCC.…”

Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

“…The efficacy and safety of three-dimensional conformal radiation therapy in augmenting the local response to sorafenib has been reported [9]. However, these studies are limited by the total irradiation dose that can be safely tolerated in patients with a higher tumor burden given the sensitivity of the normal parenchyma to radiation [12], [13].…”