Radiation therapy with phenotypic medicine: towards N-of-1 personalization

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented.