Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing

Abstract

Aim: 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.

Conclusion: 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.

Figure 1

Standard dose-survival curves of HepG2 and Hep3b fitted with standard two parameter LQ model.

Figure 2

Dose-survival curves of HepG2 and Hep3b irradiated at a low dose rate of 0.067 Gy/min fitted with incomplete repair model.

Figure 3

Effects of fractionated irradiation modeling EBRT and IMRT on survival of HepG2 and Hep3b. A: Cell survival curve of HepG2 fitted with LQ model; B: Cell survival curve of Hep3b fitted with LQ model. Cells were irradiated modeling fractionated EBRT [+] with doses of 0.0Gy, 1Gy×1, 2Gy×1, 2Gy×2, 2Gy×3, 2Gy×4 and 2Gy×5 delivered within a fraction time of 3 min, as well as modeling IMRT with the corresponding doses delivered within a fraction time of [×] 15 min, [□] 30 min or [◆] 45 min.