4D Particle Radiotherapy: A Systematic Review
Abstract
Purpose
Motion-related effects remain a critical source of uncertainty in proton and carbon ion therapy. Sharp dose gradients, combined with the inherent sensitivity of the particle range, make dose delivery particularly susceptible to temporal variations. This systematic review summarises strategies for motion management across the 4D radiotherapy workflow and aims to support alignment of clinical practice across centres and vendors.
Methods
Systematic searches of PubMed and Web of Science were performed for publications between January 2020 and December 2025 addressing 4D treatment planning and motion mitigation in particle therapy. Studies were screened by eight experts using predefined inclusion and exclusion criteria. Eligible publications were categorized into predefined key topics, and a multidisciplinary panel of 18 experts performed writing and synthesis accordingly.
Results
From 751 identified publications, 236 were included and assigned to 16 subtopics. Motion was consistently identified as a dominant contributor to uncertainty across imaging, planning, delivery, and verification. Although a wide range of 4D techniques has been proposed, clinical implementation remains highly heterogeneous. Importantly, growing clinical experience demonstrates that effective treatment of moving targets is feasible when motion is explicitly incorporated into 4D-aware clinical workflows. The clinical applicability of motion mitigation strategies is strongly dependent on local infrastructure, delivery system characteristics, and imaging capabilities. As a result, approaches effective in one institute may not be directly transferable to another. A persistent limitation is the lack of standardised methodologies for 4D dose calculation and interplay evaluation, which is particularly relevant for hypofractionated treatments and advanced delivery techniques.
Conclusion
Motion management in particle therapy is complex but clinically feasible. However, the absence of harmonised standards for 4D dose evaluation and interplay assessment limits consistent implementation. This review provides a foundation for future consensus development and guideline formation to support safe and effective treatment of moving targets with particle therapy.