Utilizing Immune Hormesis Level (IHL) as an Evaluation Tool for Immuno-activation Effects in Photon Lattice Therapies

Radiation dose and immune responses elicited by radiation therapy, particularly in Lattice therapy for large-volume tumors, represent an emerging therapeutic strategy. This study investigates the mechanisms of radiation-induced antitumor immunity and introduces the immune hormesis level (IHL) as a novel evaluation metric to replace the traditional peak-to-valley dose ratio. Unlike the peak-to-valley dose ratio, IHL standardizes dose distribution into a 0% to 100% scale by quantifying differences between peak and valley doses across isodose curves, providing a more objective and comparative indicator of immunogenic potential. Within the gross tumor volume, high-dose regions induce direct cytotoxicity and dendritic cell activation, whereas low-dose regions preserve vasculature and lymphatic drainage, enhancing both bystander and abscopal effects. Nine clinically relevant photon-based intensity modulated radiation therapy and Arc therapy (or Volumetric Modulated Arc Therapy) treatment modalities were designed and evaluated using IHL, with dose vertex size determined by photon scattering to ensure uniformity. We further derived a functional relationship between dose-sphere diameter and optimal spacing, offering a quantitative solution for tailoring Lattice therapy to tumor size. This approach provides a framework for optimizing spatial dose distributions to maximize immune stimulation, representing the most innovative contribution of this study.