Pulse-resolved tumor control probability modeling for FLASH radiotherapy using a variable-time treatment-course...

Area of Science:

• Radiation Oncology
• Radiobiology
• Computational Biology

Background:

• Current tumor control probability (TCP) models often lack resolution for FLASH radiotherapy's rapid dose delivery.
• FLASH radiotherapy utilizes unique pulse and sub-pulse temporal structures, necessitating advanced modeling.
• Integrating FLASH beam microstructure with biological factors like oxygen kinetics and repair is crucial for accurate TCP prediction.

Purpose of the Study:

• To develop TCP_LRF, a pulse-resolved extension of the Lee-Rosen TCP model (TCP_LR).
• To connect FLASH beam microstructure, oxygen/radical kinetics, biological repair, and repopulation within a treatment-course framework.
• To provide a mechanistic platform for hypothesis testing in FLASH radiotherapy.

Main Methods:

• Extended the Lee-Rosen time-dependent TCP formulation (TCP_LR) to TCP_LRF, incorporating a FLASH-aware survival term.
• Utilized a reduced-order ordinary differential equation kernel for oxygen/radical kinetics.
• Modeled each FLASH fraction as a pulse train and compared with standard-dose-rate continuous delivery.
• Verified implementation against established uniform-dose benchmarks.

Main Results:

• Conventional verification reproduced benchmark trends with minimal differences for head-and-neck, breast, and prostate cases.
• In a 3x8 Gy scenario, FLASH TCP varied significantly based on oxygen/radical kinetics (0.713-0.276).
• Standard-dose-rate delivery showed reduced TCP only under deliberately oxygen-limited conditions.

Conclusions:

• TCP_LRF offers a mechanistic treatment-course TCP platform for FLASH radiotherapy research.
• The model demonstrates that FLASH TCP is sensitive to pulse structure, repair dynamics, and oxygen availability.
• This framework allows comparative evaluation of FLASH and standard-dose-rate delivery within a unified variable-time TCP model.