Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Quantifying the effect of spatially varying factors of resistance to radiation therapy in primary brain tumors: predictions from a patient-specific model
Russell C. Rockne

Last modified: 2014-06-09


Radiation induces cell death primarily by damaging the cell’s DNA. Cells undergoing mitosis are more susceptible to radiation-induced DNA damage and therefore have a higher probability of cell death, per area per unit dose. Due to the high proliferation rate of cancer cells relative to the normal surrounding tissue, radiation is often used as a treatment for cancer. Unfortunately, a byproduct of tumor growth is the production of factors which reduce the efficacy of radiation therapy (RT). The most widely characterized mechanism of resistance to RT is reduced oxygen in the tissue, known as hypoxia, which is created when the tumor outgrows the local blood supply.
Hypoxia is known to vary within the tumor in space and in time, and may even be a byproduct of treatment. Tumor growth also produces local regions of necrosis and increased interstitial pressure which results in a spatially varying radiation effect, measured in part by the number of cells exposed per unit dose per cell cycle. Hypoxia, cell density, proliferation rate, and an intrinsic sensitivity to radiation are all independently recognized as factors which influence the impact of radiation as a cancer therapy. However, the spatial-temporal interplay of these factors vary within tumors and between patients, which creates a challenging clinical problem. I will present models of radiation-induced DNA damage and repair and tumor response to radiation therapy that are parameterized on a patient-specific basis that provide predictions of the spatial distribution of these resistance factors and their quantitative role in determining response to radiation therapy that can be tested with clinical data. I will focus on patient-specific understanding of the interplay of these factors for an aggressive and spatially heterogeneous form of a primary brain tumor known as glioblastoma.