RESUMEN
BACKGROUND: The optimal radiobiological model, which assesses the biological effects of novel radiotherapy techniques that concurrently modify multiple physical factors, has not yet been defined. This study aimed to investigate the impact of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) on cellular response in head and neck cancer and melanoma models. METHODS: Clonogenic analysis, DNA double-strand break analysis, apoptosis, and cell cycle analysis were performed on cancer stem cell models, cancer models, and normal tissue cell models to assess radiation sensitivity. RESULTS: The segmented radiation approach used in IMRT applications enhanced radiosensitivity and cytotoxicity in the cancer models, while changes in dose rate had varying effects on cytotoxicity depending on the tumor cell type. VMAT increased cellular resistance, favoring treatment outcomes. CONCLUSIONS: The biological processes were influenced differently by dose rate, IMRT, and VMAT depending on the tumor cell type. The selection of the most appropriate technique is crucial in representing new radiotherapy approaches. The obtained data can serve as a model to address clinical questions in daily practice. The integration of non-standard outcomes with standard applications should be considered in clinical settings.