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Simultaneous optimization of RBE-weighted dose and nanometric ionization distributions in treatment planning with carbon ions

Inverse treatment planning in intensity modulated particle therapy (IMPT) with scanned carbon–ion beams is currently based on the optimization of RBE-weighted dose to satisfy requirements of target coverage and limited toxicity to organs-at-risk (OARs) and healthy tissues. There are many feasible IMPT plans that meet these requirements, which allows the introduction of further criteria to narrow the selection of a biologically optimal treatment plan. We propose a novel treatment planning strategy based on the simultaneous optimization of RBE-weighted dose and nanometric ionization details (ID) as a new physical characteristic of the delivered plan beyond LET. In particular, we focus on the distribution of large ionization clusters (more than 3 ionizations) to enhance the biological effect across the target volume while minimizing biological effect in normal tissues. Carbon–ion treatment plans for different patient geometries and beam configurations generated with the simultaneous optimization strategy were compared against reference plans obtained with RBE-weighted dose optimization alone. Quality indicators, inhomogeneity index and planning volume histograms of RBE-weighted dose and large ionization clusters were used to evaluate the treatment plans. We show that with simultaneous optimization, ID distributions can be optimized in carbon–ion radiotherapy without compromising the RBE-weighted dose distributions. This strategy can potentially be used to account for optimization of endpoints closely related to radiation quality to achieve better tumor control and reduce risks of complications.