Voxel-aware oxygen kinetics resolves radiation-induced DNA damage retention across LET-oxygen conditions
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| Format: | Preprint |
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2026
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| _version_ | 1866916012480266240 |
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| author | Bolo, Renato III Fernan Bagunu, Ramon Jose C. |
| author_facet | Bolo, Renato III Fernan Bagunu, Ramon Jose C. |
| contents | Objective. Hypoxic tumor subvolumes resist radiation through elevated oxygen enhancement ratios (OER), yet no computational OER model is simultaneously particle-specific, mechanistically grounded, and fast enough for voxel-scale treatment planning. We present the VOxel-Aware Oxygen Model (VOxA) to address all three requirements.
Approach. An Oxygen Model (OM) encodes particle-specific LET-OER dependence through dual sigmoidal transitions constrained to increase monotonically with atomic number Z, combined with Michaelis-Menten oxygen kinetics. A Voxel-Aware (VA) extension resolves per-DSB local energy heterogeneity via a calibrated particle-specific sensitivity parameter. Calibrated on 233 OER observations from 29 sources across 10 particle types (LET = 0.2-654 keV/um); DSB coordinates from TOPAS-nBio simulations.
Main results. The OM achieves $R^2 = 0.719$ and MAE = 0.300 retention OER units; theoretical OER maximum 3.32 (2.4% from measurement), bootstrap median 3.37 [3.18, 4.09]. The composite $K_{\rm fix} + K_{\rm repair} = 2.82$ mmHg is tightly constrained despite high collinearity (r = 0.935). On the Furusawa heavy-ion subset, VOxA achieves 28.4% lower survival OER MAE than the clinical standard (63.1% on helium, 24.0% on carbon) and reproduces He < C < Ne Z-ordering that universal models cannot capture. The VA extension passes 18 tests confirming sample-size-invariant within-nucleus coefficient of variation of the per-DSB retention probability. VOxA evaluates in under $10^{-3}$ ms per voxel, more than $10^6$ times faster than Monte Carlo chemistry.
Significance. VOxA is the first particle-specific OER model to reproduce Z-ordering analytically at clinical planning speed, validated on the largest OER calibration dataset for this model class. Committed-break coordinates at whole-nuclear scale provide the input for inter-break topological analysis and hypoxic LET painting. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2605_12558 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Voxel-aware oxygen kinetics resolves radiation-induced DNA damage retention across LET-oxygen conditions Bolo, Renato III Fernan Bagunu, Ramon Jose C. Medical Physics Objective. Hypoxic tumor subvolumes resist radiation through elevated oxygen enhancement ratios (OER), yet no computational OER model is simultaneously particle-specific, mechanistically grounded, and fast enough for voxel-scale treatment planning. We present the VOxel-Aware Oxygen Model (VOxA) to address all three requirements. Approach. An Oxygen Model (OM) encodes particle-specific LET-OER dependence through dual sigmoidal transitions constrained to increase monotonically with atomic number Z, combined with Michaelis-Menten oxygen kinetics. A Voxel-Aware (VA) extension resolves per-DSB local energy heterogeneity via a calibrated particle-specific sensitivity parameter. Calibrated on 233 OER observations from 29 sources across 10 particle types (LET = 0.2-654 keV/um); DSB coordinates from TOPAS-nBio simulations. Main results. The OM achieves $R^2 = 0.719$ and MAE = 0.300 retention OER units; theoretical OER maximum 3.32 (2.4% from measurement), bootstrap median 3.37 [3.18, 4.09]. The composite $K_{\rm fix} + K_{\rm repair} = 2.82$ mmHg is tightly constrained despite high collinearity (r = 0.935). On the Furusawa heavy-ion subset, VOxA achieves 28.4% lower survival OER MAE than the clinical standard (63.1% on helium, 24.0% on carbon) and reproduces He < C < Ne Z-ordering that universal models cannot capture. The VA extension passes 18 tests confirming sample-size-invariant within-nucleus coefficient of variation of the per-DSB retention probability. VOxA evaluates in under $10^{-3}$ ms per voxel, more than $10^6$ times faster than Monte Carlo chemistry. Significance. VOxA is the first particle-specific OER model to reproduce Z-ordering analytically at clinical planning speed, validated on the largest OER calibration dataset for this model class. Committed-break coordinates at whole-nuclear scale provide the input for inter-break topological analysis and hypoxic LET painting. |
| title | Voxel-aware oxygen kinetics resolves radiation-induced DNA damage retention across LET-oxygen conditions |
| topic | Medical Physics |
| url | https://arxiv.org/abs/2605.12558 |