Analytical models for external photon beam radiotherapy out-of-field dose calculation: a scoping review

A growing body of scientific evidence indicates that exposure to low dose ionizing radiation (< 2 Gy) is associated with a higher risk of developing radio-induced cancer. Additionally, it has been shown to have significant impacts on both innate and adaptive immune responses. As a result, the evaluation of the low doses inevitably delivered outside the treatment fields (out-of-field dose) in photon radiotherapy is a topic that is regaining interest at a pivotal moment in radiotherapy. In this work, we proposed a scoping review in order to identify evidence of strengths and limitations of available analytical models for out-of-field dose calculation in external photon beam radiotherapy for the purpose of implementation in clinical routine. Papers published between 1988 and 2022 proposing a novel analytical model that estimated at least one component of the out-of-field dose for photon external radiotherapy were included. Models focusing on electrons, protons and Monte-Carlo methods were excluded. The methodological quality and potential limitations of each model were analyzed to assess their generalizability. Twenty-one published papers were selected for analysis, of which 14 proposed multi-compartment models, demonstrating that research efforts are directed towards an increasingly detailed description of the underlying physical phenomena. Our synthesis revealed great inhomogeneities in practices, in particular in the acquisition of experimental data and the standardization of measurements, in the choice of metrics used for the evaluation of model performance and even in the definition of regions considered out-of-the-field, which makes quantitative comparisons impossible. We therefore propose to clarify some key concepts. The analytical methods do not seem to be easily suitable for massive use in clinical routine, due to the inevitable cumbersome nature of their implementation. Currently, there is no consensus on a mathematical formalism that comprehensively describes the out-of-field dose in external photon radiotherapy, partly due to the complex interactions between a large number of influencing factors. Out-of-field dose calculation models based on neural networks could be promising tools to overcome these limitations and thus favor a transfer to the clinic, but the lack of sufficiently large and heterogeneous data sets is the main obstacle.