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Both tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose. However, the effects of radiation on the tumor and on organs at risk (OARs) are also influenced by the applied dose and volume of irradiated tissues. Combining all these biological, clinical, imaging, and dosimetric parameters in a validated prognostic or predictive model poses a major challenge. Here we aimed to provide an objective review of the potential of blood markers to guide high precision radiation therapy. A combined biological-mathematical approach opens new doors beyond prognostication of patients, as it allows truly precise oncological treatment. Indeed, the core for individualized and precision medicine is not only selection of patients, but even more the optimization of the therapeutic window on an individual basis. A holistic model will allow for determination of an individual dose-response relationship for each organ at risk for each tumor in each individual patient for the complete oncological treatment package. This includes, but is not limited to, radiotherapy alone. Individualized dose-response curves will allow for consideration of different doses of radiation and combinations with other drugs to plan for both optimal toxicity and complete response. Insights into the interactions between a multitude of parameters will lead to the discovery of new pathways and networks that will fuel new biological research on target discovery.

Blood-based biomarkers for precision medicine in lung cancer: precision radiation therapy