A mechanism-guided approach for quantifying the biological effects of tumor hypoxia in particle therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42722204.
- Also identified by DOI 10.1016/j.ijrobp.2026.09.004.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
To quantify how acute tumor hypoxia modifies the biological effectiveness of proton, helium, and carbon ions and to derive mechanistic hypoxia-compensation factors for representative spread-out Bragg peaks (SOBPs). The Monte Carlo Damage Simulation (MCDS) was used to generate DNA double-strand break (DSB) yields as functions of radiation quality q = (Z<sub>eff</sub>/β)<sup>2</sup> and oxygen level pO<sub>2</sub> (0.0001-100%). MCDS-derived DSB yields were integrated into Geant4 Monte Carlo simulations, and Repair-Misrepair-Fixation (RMF) model calculations were used to derive linear-quadratic radiosensitivity parameters. We distinguish hypoxic RBE (RBE<sub>H</sub>), which compares the biological effects of particles at reduced pO<sub>2</sub> with photons under normoxic conditions (<sup>137</sup>Cs γ-rays at pO<sub>2</sub> = 100%), from isoeffective RBE (RBE<sub>iso</sub>), which compares particles and photons at the same pO<sub>2</sub>. SOBP (10-15 cm depth) optimizations used either a uniform 2 Gy absorbed dose or a uniform RBE<sub>H</sub>-weighted dose (D<sub>RBE</sub> = 3.8 Gy) corresponding to 10% clonogenic survival in H460 cells; hypoxia reduction factors (HRFs) quantified the absorbed-dose compensation required to preserve this modeled endpoint. At pO<sub>2</sub> = 21%, at D<sub>RBE</sub> = 3.8 Gy, RBE<sub>H</sub> was 1.04-1.16 for protons, 1.23-1.67 for helium ions, and 1.84-3.55 for carbon ions. At pO<sub>2</sub> = 0.001%, RBE<sub>H</sub> decreased to 0.39-0.41, 0.50-0.70, and 0.87-2.28, respectively. Because RBE<sub>H</sub> uses the fixed photon reference at pO<sub>2</sub> = 100%, values below unity quantify the combined oxygen and radiation-quality penalty and do not indicate that particles are less effective than photons irradiating the same hypoxic tissue. At pO<sub>2</sub> = 0.001%, RBE<sub>iso</sub> remained >1 (protons 1.13-1.19; helium 1.46-2.03; carbon 2.54-6.63). The corresponding HRFs were 2.73-2.89, 2.42-2.53, and 1.57-2.07. Within the H460 single-fraction clonogenic-survival framework examined here, high-LET carbon ions are less sensitive to severe hypoxia than helium ions or protons and require smaller model-derived hypoxia-compensation factors.