arXiv subjects

Renato III Fernan Bolo

Publications and source records attributed to Renato III Fernan Bolo.

2 recordsLinked to original sources

arXiv2026

Voxel-aware oxygen kinetics resolves radiation-induced DNA damage retention across LET-oxygen conditions

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.

physics.med-ph↗

arXiv2026

Topological structure of radiation-induced DNA damage encodes coupled LET-oxygen signatures

We present the first nuclear-scale persistent homology and Random Forest classification analysis of radiation-induced DNA double-strand break (DSB) topology across the clinical particle therapy range. Using TOPAS-nBio and the Voxel-Aware Oxygen model, we generated 2,450 simulated nuclei across 49 conditions (seven particle configurations, 0.2--70.7~keV/\textmu{}m; seven oxygen levels, 0.005--21\%~O$_2$) and extracted a 107-feature matrix across seven modalities. DSB topology encodes particle identity, Spread-Out Bragg Peak (SOBP) position, and oxygen tension in a three-tier hierarchy, with fidelity at each tier governed by the physical mechanism controlling it. Particle identity and SOBP position are exactly decodable (balanced accuracy = 1.000). Oxygen-level classification degrades monotonically with LET from 0.517 (electrons) to 0.189 (carbon distal SOBP), with a charge-driven non-monotonicity at the helium-to-carbon transition confirming that atomic number, not LET alone, governs topological discriminability. The joint 49-class task achieves balanced accuracy 0.346, seventeen times above chance. Per-class recall peaks universally at 0.5\%~O$_2$ (0.788--0.976 across all configurations), which is consistent with the OER curve inflection. Topological Summaries (persistent entropy, landscape integrals) dominate oxygen encoding at all LET ($η^2_{O_2} =\,$0.300--0.622). A partial-out test reveals two mechanistically separable channels: a count-mediated scale signal ($η^2_{O_2}$ survival ratio 0.062) and a count-independent shape signal preserved or enhanced in five of seven configurations (balanced accuracy survival ratio 1.011). Persistent entropy and landscape integrals, as novel radiobiological observables, provide a computational basis for characterizing oxygen-dependent damage topology in hypoxic tumor treatment planning.

physics.med-ph↗