title: Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing.
abstract: OBJECTIVE
  To explore the impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy (IMRT) on cell killing of human hepatocellular carcinoma (HCC) HepG2 and Hep3B cell lines.
  
  
  METHODS
  The radiobiological characteristics of human HCC HepG2 and Hep3b cell lines were studied with standard clonogenic assays, using standard linear-quadratic model and incomplete repair model to fit the dose-survival curves. The identical methods were also employed to investigate the biological effectiveness of irradiation protocols modeling clinical conventional fractionated external beam radiotherapy (EBRT, fraction delivery time 3 min) and IMRT with different prolonged fraction delivery time (15, 30, and 45 min). The differences of cell surviving fraction irradiated with different fraction delivery time were tested with paired t-test. Factors determining the impact of prolonged fraction delivery time on cell killing were analyzed.
  
  
  RESULTS
  The alpha/ beta and repair half-time (T(1/2)) of HepG2 and Hep3b were 3.1 and 7.4 Gy, and 22 and 19 min respectively. The surviving fraction of HepG2 irradiated modeling IMRT with different fraction delivery time was significantly higher than irradiated modeling EBRT and the cell survival increased more pronouncedly with the fraction delivery time prolonged from 15 to 45 min, while no significant differences of cell survival in Hep3b were found between different fraction delivery time protocols.
  
  
  CONCLUSIONS
  The prolonged fraction delivery time modeling IMRT significantly decreased the cell killing in HepG2 but not in Hep3b. The capability of sub-lethal damage repair was the predominant factor determining the cell killing decrease. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments for HCC.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, The Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Zheng
authors.forename: Long-Hua
authors.initials: LH
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Yan
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal