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

BACKGROUND: 
 Approximately 50% of all colorectal cancer (CRC) patients will develop metastasis to the liver. <sup>90</sup>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 <sup>90</sup>Y β<sup>-</sup> radiation exposure, and thus the relative effectiveness of 90Y SIRT in relation to external beam radiotherapy (EBRT).
 Methods: A <sup>90</sup>Y-source dish was sandwiched between culture dishes to irradiate DLD-1 or HT-29 cells for a period of 6 days. Cell survival was determined by clonogenic assay. Dose absorbed per <sup>90</sup>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 α and β using R. These results were compared to radiosensitivity parameters determined for 6 MV clinical x-rays and 137Cs γ-rays exposure. Equivalent dose of EBRT in 2 Gy (EQD2) and 10 Gy (EQD10) fractions were derived for <sup>90</sup>Y dose.
 Results: HT-29 cells were more radioresistant than DLD-1 for all treatment modalities. Radiosensitivity parameters determined for 6 MV x-rays and 137Cs γ-rays were equivalent for both cell lines. The α/β ratio for <sup>90</sup>Y β<sup>-</sup>-particle exposure was over an order of magnitude higher than the other two modalities due to protraction of dose delivery. Consequently, an <sup>90</sup>Y SIRT absorbed dose of 60 Gy equates to an EQD2 of 28.7 and 54.5 Gy and an EQD10 of 17.6 and 19.3 Gy for DLD-1 and HT-29 cell lines, respectively.
 Conclusion: We derived radiosensitivity parameters for two CRC cell lines exposed to <sup>90</sup>Y, 6 MV x-rays, and 137Cs γ-rays irradiation. These radiobiological parameters are critical to understanding the dose response of CRC lesions and ultimately informs the efficacy of <sup>90</sup>Y SIRT relative to other radiation therapy modalities.