Shang-Wen Chen1, Li-Ching Lin2, Yu-Cheng Kuo3, Ji-An Liang4, Chia-Chun Kuo5, Jeng-Fong Chiou6. 1. Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan. Electronic address: sjfchiou@gmail.com. 2. Department of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan. 3. Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan. 4. Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan. 5. Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan. 6. Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan.
Abstract
PURPOSE: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. RESULTS: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. CONCLUSIONS: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.
PURPOSE: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. RESULTS: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. CONCLUSIONS: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.
Authors: D Bossé; T Ng; C Ahmad; A Alfakeeh; I Alruzug; J Biagi; J Brierley; P Chaudhury; S Cleary; B Colwell; C Cripps; L A Dawson; M Dorreen; E Ferland; P Galiatsatos; S Girard; S Gray; F Halwani; N Kopek; A Mahmud; G Martel; L Robillard; B Samson; M Seal; J Siddiqui; L Sideris; S Snow; M Thirwell; M Vickers; R Goodwin; R Goel; T Hsu; E Tsvetkova; B Ward; T Asmis Journal: Curr Oncol Date: 2016-12-21 Impact factor: 3.677
Authors: Erqi L Pollom; Lei Deng; Reetesh K Pai; J Martin Brown; Amato Giaccia; Billy W Loo; David B Shultz; Quynh Thu Le; Albert C Koong; Daniel T Chang Journal: Int J Radiat Oncol Biol Phys Date: 2015-07-01 Impact factor: 7.038