Towards harmonizing clinical linear energy transfer (LET) reporting in proton radiotherapy: a European multi-centric study

Abstract

Background

Clinical data suggest that the relative biological effectiveness (RBE) in proton therapy (PT) varies with linear energy transfer (LET). However, LET calculations are neither standardized nor available in clinical routine. Here, the status of LET calculations among European PT institutions and their comparability are assessed.

Materials and methods

Eight European PT institutions used suitable treatment planning systems with their center-specific beam model to create treatment plans in a water phantom covering different field arrangements and fulfilling commonly agreed dose objectives. They employed their locally established LET simulation environments and procedures to determine the corresponding LET distributions. Dose distributions D_1.1 and D_RBE assuming constant and variable RBE, respectively, and LET were compared among the institutions. Inter-center variability was assessed based on dose- and LET-volume-histogram parameters.

Results

Treatment plans from six institutions fulfilled all clinical goals and were eligible for common analysis. D_1.1 distributions in the target volume were comparable among PT institutions. However, corresponding LET values varied substantially between institutions for all field arrangements, primarily due to differences in LET averaging technique and considered secondary particle spectra. Consequently, D_RBE using non-harmonized LET calculations increased inter-center dose variations substantially compared to D_1.1 and significantly in mean dose to the target volume of perpendicular and opposing field arrangements (p < 0.05). Harmonizing LET reporting (dose-averaging, all protons, LET to water or to unit density tissue) reduced the inter-center variability in LET to the order of 10–15% within and outside the target volume for all beam arrangements. Consequentially, inter-institutional variability in D_RBE decreased to that observed for D_1.1.

Conclusion

Harmonizing the reported LET among PT centers is feasible and allows for consistent multi-centric analysis and reporting of tumor control and toxicity in view of a variable RBE. It may serve as basis for harmonized variable RBE dose prescription in PT.

Keywords:

• Proton therapy
• multi-centric study
• linear energy transfer (LET)
• relative biological effectiveness (RBE)

Disclosure statement

JÖ is employed as a Researcher at RaySearch Laboratories. The other authors report no conflict of interest.

Additional information

Funding

This project was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No [730983] (INSPIRE); the Engineering and Physical Sciences Research Council (Grand Challenge Network + in Proton Therapy) [grant number EP/N027167/1]; the Engineering and Physical Sciences Research Council (BioProton) [grant number EP/S024344/1); the Science and Technology Facilities Council (Global Challenge Network + in Advanced Radiotherapy) [grant number ST/N002423/1]; the Christie Charitable Fund and co-funded by the NIHR Manchester Biomedical Research Centre [BRC-1215-20007].