Demonstration of bystander response in high dose technique of grid using theoretical calculation by linear quadratic model along with experimental investigations

The Linear Quadratic (LQ) equation as the most common formula in radiotherapy has a debatable accuracy in modeling high-dose effects. The purpose of this study was to demonstrate bystander response of the Grid treatment in SCC cell line, based on both theoretical calculations and experimental investigations.

The linear quadratic model was used to calculate the equivalent uniform dose (EUD) of a Grid-field with the 10 Gy maximum doses. According to the EUD definition, the identical tumor survival fraction (SF) was expected to obtain from both Grid and open-field single fraction. After observing the difference, the clonogenic and apoptosis assays were exerted to investigate bystander response via medium transfer strategy which was performed from 10Gy-irradiated donors to 1.5Gy-irradiated recipients.

The EUD was equal to 4 Gy and the SF of 4 Gy EUD and 10 Gy Grid-field were 0.1 ± 0.02 and 0.051 ± 0.008, respectively. These findings contradicted the theoretical expectations of their survivals equality. Moreover, the bystander clonogenic cells death enhanced approximately by 2.91 times (statistically significant); highlighting the bystander response role. The apoptotic findings illustrated that the bystander cells experienced an approximately 10% increase and the apoptotic rate confirmed the clonogenic survival result which was less in the EUD than the Grid-field.

Since the SF of the Grid-field was less than the EUD, it revealed the Grid therapeutic advantages plus bystander response manifestation; that was ignored in the LQ equation and may not be demonstrated by sheer theoretical calculations of the modulated-field.