Tumor Hypoxia Heterogeneity Affects Radiotherapy: Inverse-Percolation Shell-Model Monte Carlo Simulations.

Area of Science:

• Oncology
• Medical Physics
• Radiation Biology

Background:

• Tumor hypoxia, the lack of oxygen within tumors, has been known for a century and is recognized to interfere with radiotherapy.
• Hypoxia is not uniform within tumors, presenting heterogeneity that can significantly affect treatment outcomes.

Purpose of the Study:

• To investigate the extreme effects of tumor hypoxia heterogeneity on radiotherapy and combination radiochemotherapy.
• To model the impact of oxygen diffusion gradients on cell-kill probability and tumor network disruption.

Main Methods:

• Utilized Monte Carlo simulations to model radiotherapy-induced tumor/TME network break-up using an inverse percolation physics model in a shell-like medium.
• Quantified the gradient of radiative cell-kill probability from tumor periphery to center due to decreasing hypoxia.
• Analyzed the variability of critical percolation concentration and its relationship with space removal probability.

Main Results:

• Observed a decrease in hypoxia from the tumor periphery to the center, creating a gradient of cell-kill probability.
• Demonstrated that increased probability of space removal in different shells leads to a higher critical threshold for tumor break-up.
• Indicated that a significantly larger radiation dose than expected may be required for effective tumor break-up.

Conclusions:

• Tumor hypoxia heterogeneity necessitates higher radiation doses for effective tumor destruction.
• Understanding TME hypoxia heterogeneity can pave the way for personalized precision radiation oncology.
• The findings have critical implications for optimizing radiotherapy and combination radiochemotherapy strategies.