Journal
FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.811415
Keywords
radiobiology; glioma; computational biology; mathematical modeling; oncology; brain cancer cell
Categories
Ask authors/readers for more resources
This study proposes and validates a time-resolved mathematical model to predict the changes in tumor response to fractionated radiation. By experimentally verifying the model, it establishes a framework for quantitative characterization and prediction of the dynamic radiobiological response of gliomas to fractionated radiotherapy.
PurposeConventional radiobiology models, including the linear-quadratic model, do not explicitly account for the temporal effects of radiation, thereby making it difficult to make time-resolved predictions of tumor response to fractionated radiation. To overcome this limitation, we propose and validate an experimental-computational approach that predicts the changes in cell number over time in response to fractionated radiation. MethodsWe irradiated 9L and C6 glioma cells with six different fractionation schemes yielding a total dose of either 16 Gy or 20 Gy, and then observed their response via time-resolved microscopy. Phase-contrast images and Cytotox Red images (to label dead cells) were collected every 4 to 6 hours up to 330 hours post-radiation. Using 75% of the total data (i.e., 262 9L curves and 211 C6 curves), we calibrated a two-species model describing proliferative and senescent cells. We then applied the calibrated parameters to a validation dataset (the remaining 25% of the data, i.e., 91 9L curves and 74 C6 curves) to predict radiation response. Model predictions were compared to the microscopy measurements using the Pearson correlation coefficient (PCC) and the concordance correlation coefficient (CCC). ResultsFor the 9L cells, we observed PCCs and CCCs between the model predictions and validation data of (mean +/- standard error) 0.96 +/- 0.007 and 0.88 +/- 0.013, respectively, across all fractionation schemes. For the C6 cells, we observed PCCs and CCCs between model predictions and the validation data were 0.89 +/- 0.008 and 0.75 +/- 0.017, respectively, across all fractionation schemes. ConclusionBy proposing a time-resolved mathematical model of fractionated radiation response that can be experimentally verified in vitro, this study is the first to establish a framework for quantitative characterization and prediction of the dynamic radiobiological response of 9L and C6 gliomas to fractionated radiotherapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available