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Advancing Proton Therapy: Integration of Minibeam Spatial Fractionation and FLASH Dose Rates.

Yuting Lin¹, Wei Wu², Jufri Setianegara³

¹The University of Texas Southwestern Medical Center.

Research Square

|December 11, 2025

Summary

Integrating proton minibeam radiation therapy (pMBRT) with ultra-high-dose-rates (UHDR) significantly reduces treatment times from minutes to seconds. This advancement enhances dose delivery efficiency for pMBRT, paving the way for improved cancer treatment.

Keywords:

FLASH Minibeam Pencil Beam Scanning Spatially Fractioned Radiation Therapy

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Area of Science:

Medical Physics
Radiation Oncology
Biomedical Engineering

Background:

Proton minibeam radiation therapy (pMBRT) offers precise dose distribution for reduced normal tissue toxicity.
High monitor unit (MU) requirements of multi-slit collimators (MSCs) lead to prolonged treatment times.
Integrating pMBRT with ultra-high-dose-rates (UHDR) is explored to overcome delivery time limitations and enhance therapeutic index.

Purpose of the Study:

To investigate the feasibility of combining pMBRT with UHDR (FLASH) proton therapy.
To assess the impact of FLASH dose rates on pMBRT dose distributions and delivery times.
To evaluate the potential for improved therapeutic ratio and clinical applicability.

Main Methods:

Utilized an IBA Proteus®ONE proton therapy system with 6.5 cm and 10 cm thick MSCs.
Achieved FLASH delivery using 228 MeV protons at 125 nA; clinical beams used 226 MeV at 1-5 nA.
Compared dose measurements (Gafchromic films, Monte Carlo simulations) and delivery times for FLASH vs. clinical beams.

Main Results:

pMBRT dose distributions were successfully achieved under FLASH dose rates, reducing treatment time to 2.5 seconds (vs. 3 minutes for clinical beams).
The 10 cm collimator yielded higher peak-to-valley dose ratios (PVDRs) at 2 cm depth (4.36) compared to the 6.5 cm collimator (2.57).
Demonstrated potential for improved dose delivery efficiency while maintaining spatial resolution and dose modulation.

Conclusions:

Confirmed the feasibility of integrating pMBRT with FLASH dose rates on a clinical proton therapy system.
Addressed delivery time challenges, enabling efficient spatial fractionation with UHDR.
This integration offers a pathway for clinical translation of pMBRT with FLASH for precise, high-dose cancer therapy.