Abstract
Modern radiotherapy (RT) can deliver radiation with remarkable geometric precision through advances in imaging, treatment planning, and delivery systems. However, treatment outcomes remain limited by tumor biology. Radioresistant tumors, intratumoral heterogeneity, and normal tissue toxicity restrict the ability to improve outcomes by simply increasing dose. New approaches are therefore needed to enhance the biological effectiveness of RT without dose escalation.This dissertation investigates the use of low-intensity, non-ionizing electric and magnetic fields as adjuncts to photon radiotherapy. Unlike conventional therapies, these fields do not rely on ionization or heating but can still interact with biological systems and influence cellular behavior. Custom electric- and magnetic-field delivery platforms were developed to enable controlled exposure during radiation treatment. Finite element modeling was used to characterize field distributions and demonstrated that field behavior depends strongly on geometry and tissue electrical properties. Biological studies revealed distinct responses to the two modalities. Electric field exposure alone did not significantly affect clonogenic survival in-vitro. However, when combined with radiation in-vivo, electric fields reduced tumor growth and improved survival, suggesting effects that emerge at the tissue level. In contrast, magnetic field exposure reduced clonogenic survival in-vitro, and combination treatment produced greater effects consistent with radiosensitization.These findings demonstrate that low-intensity electric and magnetic fields may enhance radiotherapy without increasing radiation dose. This work establishes a preclinical foundation for understanding field-mediated modulation of radiation response and supports future studies focused on mechanism discovery, parameter optimization, and clinical translation.