Critical Analysis of the Uncertainties in Translational and Radiobiology Studies as a Basis for Radiotherapy

The integration of all the steps involved in the treatment process is quite complex, as it involves the correct knowledge of the dose‒response curves developed in laboratory experiments, the translation of these results to the clinic, the adequate delineation of the tumor, and the appropriate dose prescribed for each type of tumor and delivered daily to the patient. For example, the correct assessment of the dose administered to a patient strongly depends on an interconnected chain of steps executed harmoniously, as the accuracy of a given dosimetry procedure is very high. In this case, the measurement results must be ensured to represent the best possible reported values with their typical uncertainties to allow clinical results to be achieved and to be comparable with those of other institutions. The robustness of the chain of events is often fragile, with uncertainties at each stage sometimes not considered or sometimes difficult to estimate, requiring different conceptual and statistical approaches at various times in the decision-making process. As a result, as the additive sequence of uncertainties is generally not fully considered, the clinical outcome may not be as anticipated. The objective of this review is to critically and constructively highlight the weak points observed in the interrelationship of some of all steps that ultimately lead to better tumor control and, ultimately, to provoke a reflection on the theme