Radiosensitivity of colorectal cancer to 90 Y and the radiobiological implications for radioembolisation therapy.

Approximately 50% of all colorectal cancer (CRC) patients will develop metastasis to the liver. Y-90 selective internal radiation therapy (SIRT) is an established treatment for metastatic CRC. There is still a fundamental lack of understanding regarding the radiobiology underlying the dose response. This study was designed to determine the radiosensitivity of two CRC cell lines (DLD-1 and HT-29) to Y-90 beta(-) radiation exposure, and thus the relative effectiveness of Y-90 SIRT in relation to external beam radiotherapy (EBRT). A Y-90-source dish was sandwiched between culture dishes to irradiate DLD-1 or HT-29 cells for a period of 6 d. Cell survival was determined by clonogenic assay. Dose absorbed per Y-90 disintegration was calculated using the PENELOPE Monte Carlo code. PENELOPE simulations were benchmarked against relative dose measurements using EBT3 GAFchromic (TM) film. Statistical regression based on the linear-quadratic model was used to determine the radiosensitivity parameters alpha and beta using R. These results were compared to radiosensitivity parameters determined for 6 MV clinical x-rays and Cs-137 gamma-ray exposure. Equivalent dose of EBRT in 2 Gy (EQD2) and 10 Gy (EQD10) fractions were derived for Y-90 dose. HT-29 cells were more radioresistant than DLD-1 for all treatment modalities. Radiosensitivity parameters determined for 6 MV x-rays and Cs-137 gamma-ray were equivalent for both cell lines. The alpha/beta ratio for Y-90 beta(-) -particle exposure was over an order of magnitude higher than the other two modalities due to protraction of dose delivery. Consequently, an Y-90 SIRT absorbed dose of 60 Gy equates to an EQD2 of 28.7 and 54.5 Gy and an EQD 10 of 17.6 and 19.3 Gy for DLD-1 and HT-29 cell lines, respectively. We derived radiosensitivity parameters for two CRC cell lines exposed to Y-90 beta(-) -particles, 6 MV x-rays, and Cs-137 gamma-ray irradiation. These radiobiological parameters are critical to understanding the dose response of CRC lesions and ultimately informs the efficacy of Y-90 SIRT relative to other radiation therapy modalities.