Experimental validation of theoretical survival models for high radiation doses in cell lines of different types of cancer

PERONA, MARINA; BOUREL, VICTOR; DURÁN, HEBE; OLIVADOTTI, MARÍA DEL CIELO; GRISSI, CECILIA; JUVENAL, GUILLERMO; CAPOULAT, MARÍA EUGENIA; MECA CASTRO, EDWARD; IBAÑEZ, IRENE L.

Mar del Plata

Congreso; LXIV Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), LI Reunión Anual de la SAFE, XXI Reunión Anual de la SAB)y XXXI Reunión Anual de la SAP 2019; 2019

SAIC. SAFE. SAB. SAP Participan AACYTAL. NANOMED-AR. HCS

Technological advances in radiotherapy enable radiation dose to be delivered in a highly conformal manner, protecting healthy tissues. Clinical interest in hypofractionation requires new models to predict tumor response to higher dose per fraction than that used in conventional radiotherapy (2Gy). The linear-quadratic model e-(aD+bD2) (LQ) is a useful tool to compare conventional fractionations. However, LQ curve bends continuously on the log-linear plot resulting in the underestimation of survival for high doses. It has been demonstrated that LQ fits well for doses lower than 7Gy. Theoretical models have been described to introduce corrections to LQ for high doses, such as the linear-quadratic-cubic (LQC), the linear-quadratic-linear (LQL) and the Universal (USC) models. The aim of this work was to experimentally validate these models by fitting survival curves up to high doses in cell lines of different types of cancer. Survival curves were obtained by clonogenic assay after irradiating thyroid (TPC-1 y FRTL-5), breast (T47D) and lung (A549) cancer cells with a gamma source (137Cs). Survival curves were fitted to the LQ model by weighted least squares in the low dose region, obtaining a and b parameters. These values were compared with those obtained for high doses using the LQL, LQC and USC models. Results showed that for curves fitted to LQL, parameters values were a=(0,50±0.07)Gy-1 , b=(0,020±0,013)Gy-2 and g=(0,71±0,15)Gy-1 (for TPC-1 cells); and a=(0,17±0,04)Gy-1 , b=(0,040±0,009)Gy-2 and g=(0,84±0,16)Gy-1 (for T47-D cells). For curves fitted to LQC the values were a=(0,19±0,03)Gy-1 , b=(0,029±0,007)Gy-2 and g=(0,0005±0,0001)Gy-1 (for FRTL-5 cells). A549 fitted parameters are in process.We conclude that for the evaluated cell lines, the quadratic linear model fits well up to doses of 8 Gy and for higher doses, the theoretical model that best fits varies according to the different cell lines, demonstrating a different behavior between different tumor cells.