# Microstructural modelling based on diffusion weighted imaging to guide dose painting in carbon ions for large sacral chordomas

## TL;DR

This study shows that using diffusion-weighted imaging to guide dose painting in carbon ion radiotherapy can improve tumor control while protecting nearby organs.

## Contribution

A novel dose painting approach using microstructural modeling and diffusion-weighted imaging in carbon ion radiotherapy for sacral chordomas.

## Key findings

- Dose escalation improved tumor control probability by 7.8 percentage points.
- Dose redistribution plans showed a 1.8 percentage point increase in tumor control probability.
- Plans were robust to cell count uncertainties, with minimal impact on tumor control probability variations.

## Abstract

•Diffusion-weighted imaging enabled dose painting in carbon ion radiotherapy.•Average tumor control probability increased by 7.8 pp, ensuring organ sparing.•Plans were robust to cell count uncertainties, limiting variations in tumor control.•Linear energy transfer optimization was less effective in biologically targeted plans.

Diffusion-weighted imaging enabled dose painting in carbon ion radiotherapy.

Average tumor control probability increased by 7.8 pp, ensuring organ sparing.

Plans were robust to cell count uncertainties, limiting variations in tumor control.

Linear energy transfer optimization was less effective in biologically targeted plans.

Dose Painting (DP) in radiotherapy is a strategy to account for the tumor microstructural heterogeneity. This study evaluated a DP approach in carbon ion radiotherapy (CIRT), using cell count estimates derived from diffusion-weighted magnetic resonance imaging (DWI).

Thirty-seven large sacral chordoma (SC) patients were analysed. Voxel-wise cell count was estimated from DWI using a published microstructural model. A Poisson-based tumor control probability (TCP) model, fitted on 27 patients, guided DP optimization in a research version of RayStation 2024A. The approach was tested on 10 patients, comparing uniform-dose plans against two strategies: dose redistribution (DR), which maintained the mean gross tumor volume (GTV) dose, and dose escalation (DE), which allowed a 3 % increase. Plan evaluation on targets and organs at risk (OARs) included dose-volume histogram metrics (D95%, D50%, D1%) and dose-averaged linear energy transfer (LETd)-volume histogram metrics (L98%, L50%, L1%) to assess clinical acceptability. TCP gain quantified the benefit of biologically targeted strategies. TCP uncertainty was evaluated by propagating the microstructural model’s errors to generate best- and worst-case cell count maps.

DE and DR plans met clinical acceptability criteria. DE increased TCP from 75.5 ± 5.6 % to 83.3 ± 3.9 % (p < 0.001), with −3 to +5 percentage points variation under uncertainty. DR plans showed a TCP gain of 1.8 ± 1.0 percentage points. No significant dose or LETd increase was observed in OARs, while DE plans showed a lower L98% in GTV.

Dose painting based on microstructural modelling in CIRT showed potential to improve TCP while sparing OARs.