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. (90)Y 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 (90)Y β(−) radiation exposure, and thus the relative effectiveness of (90)Y SIRT in relation to external beam radiotherapy (EBRT). A (90)Y-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 (90)Y disintegration was calculated using the PENELOPE Monte Carlo code. PENELOPE simulations were benchmarked against relative dose measurements using EBT3 GAFchromic(™) film. Statistical regression based on the linear-quadratic model was used to determine the radiosensitivity parameters [Image: see text] and [Image: see text] using R. These results were compared to radiosensitivity parameters determined for 6 MV clinical x-rays and (137)Cs γ-ray exposure. Equivalent dose of EBRT in 2 Gy ([Image: see text]) and 10 Gy ([Image: see text]) fractions were derived for (90)Y dose. HT-29 cells were more radioresistant than DLD-1 for all treatment modalities. Radiosensitivity parameters determined for 6 MV x-rays and (137)Cs γ-ray were equivalent for both cell lines. The [Image: see text] ratio for (90)Y β(−)-particle exposure was over an order of magnitude higher than the other two modalities due to protraction of dose delivery. Consequently, an (90)Y SIRT absorbed dose of 60 Gy equates to an [Image: see text] of 28.7 and 54.5 Gy and an [Image: see text] 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 (90)Y β(−)-particles, 6 MV x-rays, and (137)Cs γ-ray irradiation. These radiobiological parameters are critical to understanding the dose response of CRC lesions and ultimately informs the efficacy of (90)Y SIRT relative to other radiation therapy modalities.