Voxel-aware oxygen kinetics resolves radiation-induced DNA damage retention across LET-oxygen conditions
Abstract
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 R2 = 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 Kfix + Krepair = 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 106 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.
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BibTeX
@misc{bolo2026voxelaware,
title = {{Voxel-aware oxygen kinetics resolves radiation-induced DNA damage retention across LET-oxygen conditions}},
author = {Renato III Fernan Bolo and Ramon Jose C. Bagunu},
howpublished = {arXiv},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2605.12558},
eprint = {2605.12558},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2605.12558},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - UNPB
TI - Voxel-aware oxygen kinetics resolves radiation-induced DNA damage retention across LET-oxygen conditions
AU - Renato III Fernan Bolo
AU - Ramon Jose C. Bagunu
PY - 2026
DA - 2026/09/04
PB - arXiv
DO - 10.48550/arxiv.2605.12558
UR - https://arxiv.org/abs/2605.12558
AB - 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_fix + K_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.
ER -