Fifty-seventh annual meeting of the American association of physicists in medicine
SU-E-T-664: Radiobiological Modeling of Prophylactic Cranial Irradiation in Mice
Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with ALL and SCLC, and we have shown the potential of PCI in select breast cancer patients through a mouse model (manuscript in preparation). We developed a computational model using our experimental results to demonstrate the advantage of treating brain micro-metastases early.
MATLAB was used to develop the computational model of brain metastasis and PCI in mice. The number of metastases per mouse and the volume of metastases from four- and eight-week endpoints were fit to normal and log-normal distributions, respectively. Model input parameters were optimized so that model output would match the experimental number of metastases per mouse. A limiting dilution assay was performed to validate the model. The effect of radiation at different time points was computationally evaluated through the endpoints of incidence, number of metastases, and tumor burden.
The correlation between experimental number of metastases per mouse and the Gaussian fit was 87% and 66% at the two endpoints. The experimental volumes and the log-normal fit had correlations of 99% and 97%. In the optimized model, the correlation between number of metastases per mouse and the Gaussian fit was 96% and 98%. The log-normal volume fit and the model agree 100%. The model was validated by a limiting dilution assay, where the correlation was 100%. The model demonstrates that cells are very sensitive to radiation at early time points, and delaying treatment introduces a threshold dose at which point the incidence and number of metastases decline.
We have developed a computational model of brain metastasis and PCI in mice that is highly correlated to our experimental data. The model shows that early treatment of subclinical disease is highly advantageous.