The first clinical prototype for proton minibeam radiation therapy

Spatially Fractionated Radiation Therapy (SFRT) represents a significant advancement over conventional radiation therapy (CONV) by delivering a highly modulated spatial dose pattern, characterized by the peak- valley dose ratio (PVDR). Preclinical and clinical studies have demonstrated that SFRT substantially enhances the therapeutic index by improving normal tissue dose tolerance and tumor control efficacy compared to CONV. The clinical adoption of SFRT is rapidly expanding, now encompassing a variety of disease sites beyond bulky advanced tumors. This project focuses on proton minibeam RT (pMBRT), a versatile SFRT modality that is not yet clinically available, despite compelling evidence from biological studies highlighting its potential to further reduce radiation-induced normal tissue toxicity and improve tumor control compared to CONV and clinically available SFRT techniques. The overarching goal of this project is to develop the first clinical pMBRT prototype and innovative pMBRT methods to drive its clinical translation. This project leverages a well-established academic-industrial partnership (AIP) between KUMC and RaySearch. As RaySearch, the world’s leading TPS company, offers the globally used RayStation TPS, this AIP ensures the seamless translation of project outcomes to end-users, promoting clinical adoption and widespread application of pMBRT for patient benefit. This project introduces three major innovations. (1) First clinical pMBRT prototype: Building upon our preclinical pMBRT system [115,131], this project will develop the first clinical pMBRT prototype, fully integrated with RayStation TPS. This milestone will facilitate patient treatment and pave the way for widespread clinical implementation. (2) Multi-collimator pMBRT (MC-pMBRT): A fundamental challenge for implementing pMBRT in patients is how to achieve sufficient PVDR while maintaining dose objectives. To address this, this project introduces MC-pMBRT, a novel method that uses multiple pre-made, general-purpose collimators with varying minibeam geometries to jointly optimize dose and PVDR. (3) Minibeam-LATTICE: The original form of pMBRT delivers a uniform target dose. This project introduces minibeam-LATTICE, a novel SFRT modality that leverages minibeams to achieve a lattice dose pattern in the target, enabling the treatment of small-to-medium tumor targets that are unsuitable for current clinically available SFRT modalities due to their large beam size. Significance: The completion of the project will provide (1) the first clinical pMBRT prototype integrated with RayStation TPS, enabling patient trials, and (2) novel pMBRT methods, such as minibeam-LATTICE, to expand SFRT’s clinical utility to small-to-medium tumor targets, where current clinically available SFRT cannot provide a spatially-modulated dose pattern due to their large beamlet size. These advancements will enhance the therapeutic potential of SFRT, offering broader treatment options and improved outcomes for patients. Project Number: 1R37CA306829-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Yuting Lin | Institution: UT SOUTHWESTERN MEDICAL CENTER, DALLAS, TX | Award Amount: $683,885 | Activity Code: R37 | Study Section: Special Emphasis Panel[ZRG1 CTH-E (57)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11259797