Spatial descriptions of radiotherapy dose: Normal tissue complication models and statistical associations

For decades, dose-volume information for segmented anatomy has provided the essential data for correlating radiotherapy dosimetry with treatment-induced complications. Dose-volume information has formed the basis for modelling those associations via normal tissue complication probability (NTCP) models and for driving treatment planning. Limitations to this approach have been identified. Many studies have emerged demonstrating that the incorporation of information describing the spatial nature of the dose distribution, and potentially its correlation with anatomy, can provide more robust associations with toxicity and seed more general NTCP models. Such approaches are culminating in the application of computationally intensive processes such as machine learning and the application of neural networks. The opportunities these approaches have for individualising treatment, predicting toxicity and expanding the solution space for radiation therapy are substantial and have clearly widespread and disruptive potential. Impediments to reaching that potential include issues associated with data collection, model generalisation and validation. This review examines the role of spatial models of complication and summarises relevant published studies. Sources of data for these studies, appropriate statistical methodology frameworks for processing spatial dose information and extracting relevant features are described. Spatial complication modelling is consolidated as a pathway to guiding future developments towards effective, complication-free radiotherapy treatment.