Physical Basis of Spatial Safety Boundaries in Intratumoral Chlorine Dioxide Ablation — Evidence from Ex Vivo Porcine Liver and a Real-World Feline Tumor Case

This work investigates the physical basis of spatial safety boundaries in intratumoral chlorine dioxide (ClO₂) ablation. Using ex vivo porcine liver tissue together with an observational real-world feline mammary tumor case, the study shows that the macroscopic alteration domain is established during the injection phase and is primarily determined by pressure-driven convection, tissue compliance, and volume-defined percolation, whereas post-injection processes (whitening, consolidation, necrosis) do not further propagate the outer boundary. The results support a biophysical interpretation in which the spatial occupation volume formed during delivery defines a predictable and confined treatment domain, consistent with a dose-to-radius (volume-locked) relationship, with minimal extension into surrounding normal tissue. This work provides a mechanistic framework for interpreting tissue-scale transport and safety constraints in intratumoral chemical ablation, and may inform the design, optimization, and future clinical translation of localized ROS-based interventions. This work is a conceptual and mechanistic preprint based on ex vivo experiments and a single real-world tumor case; the framework remains subject to further in vivo and clinical validation. Version 2 note: Corrected a labeling error in Figure 2 (“7 hours post-injection”). No changes were made to the data, analysis, or conclusions.