## Abstract

Background: Large tumor size has been reported as a predicting factor for inferior clinical outcome in carbon ion radiotherapy (CIRT). Besides the clinical factors accompanied with such tumors, larger tumors receive typically more low linear energy transfer (LET) contributions than small ones which may be the underlying physical cause. Although dose averaged LET is often used as a single parameter descriptor to quantify the beam quality, there is no evidence that this parameter is the optimal clinical predictor for the complex mixed radiation fields in CIRT. Purpose: Purpose of this study was to investigate on a novel dosimetric quantity, namely high-LET-dose ((Formula presented.), the physical dose filtered based on an LET threshold) as a single parameter estimator to differentiate between carbon ion treatment plans (cTP) with a small and large tumor volume. Methods: Ten cTPs with a planning target volume, (Formula presented.) (large) and nine with a (Formula presented.) (small) were selected for this study. To find a reasonable LET threshold ((Formula presented.)) that results in a significant difference in terms of (Formula presented.), the voxel based normalized high-LET-dose ((Formula presented.)) distribution in the clinical target volume (CTV) was studied on a subset (12 out of 19 cTPs) for 18 LET thresholds, using standard distribution descriptors (mean, variance and skewness). The classical dose volume histogram concept was used to evaluate the (Formula presented.) and (Formula presented.) distributions within the target of all 19 cTPs at the before determined (Formula presented.). Statistical significance of the difference between the two groups in terms of mean (Formula presented.) and (Formula presented.) volume histogram parameters was evaluated by means of (two-sided) t-test or Mann-Whitney-U-test. In addition, the minimum target coverage at the above determined (Formula presented.) was compared and validated against three other thresholds to verify its potential in differentiation between small and large volume tumors. Results: An (Formula presented.) of approximately (Formula presented.) was found to be a reasonable threshold to classify the two groups. At this threshold, the (Formula presented.) and (Formula presented.) were significantly larger ((Formula presented.)) in small CTVs. For the small tumor group, the near-minimum and median (Formula presented.) (and (Formula presented.)) in the CTV were in average (Formula presented.) (0.31 ± 0.08) and (Formula presented.) (0.46 ± 0.06), respectively. For the large tumors, these parameters were (Formula presented.) (0.20 ± 0.01) and (Formula presented.) (0.28 ± 0.02). The difference between the two groups in terms of mean near-minimum and median (Formula presented.) ((Formula presented.)) was 2.7 Gy (11%) and 5.0 Gy (18%), respectively. Conclusions: The feasibility of high-LET-dose based evaluation was shown in this study where a lower (Formula presented.) was found in cTPs with a large tumor size. Further investigation is needed to draw clinical conclusions. The proposed methodology in this work can be utilized for future high-LET-dose based studies.

Original language | English |
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Journal | Medical Physics |

Early online date | 20 Sept 2023 |

DOIs | |

Publication status | E-pub ahead of print - 20 Sept 2023 |

## Keywords

- LET-based filtered dose
- carbon ion radiotherapy
- dirty dose
- high-LET-dose
- treatment plan evaluation

## ASJC Scopus subject areas

- Biophysics
- Radiology, Nuclear Medicine and Imaging