PRESTO

PRoton therapy Enhancement by Spatially fractionated Treatment Optimization

Project objectives and goals

Proton therapy is increasingly used worldwide as a precise form of radiation treatment that can better spare healthy tissues compared to conventional radiotherapy. Nevertheless, side effects remain a challenge, as high doses are often required to control tumours while surrounding normal tissues remain at risk. To further improve outcomes, new strategies are needed that can reduce treatment-related complications without compromising tumour control.

PRESTO investigates a novel way of delivering proton therapy known as proton minibeam radiation therapy (pMBRT). Unlike conventional proton therapy, pMBRT introduces a spatially fractionated beam pattern that can spare normal tissues while still delivering a full tumour dose. PRESTO focuses on achieving a homogeneous dose within the target volume to ensure effective tumour control while maintaining the spatial fractionation pattern that protects normal tissues. This approach simplifies translation into clinical practice, enables direct comparison with conventional proton therapy, and allows a clear evaluation of reductions in normal tissue toxicity.

Our early preclinical studies using specially designed multislit collimators have shown very promising results, with a marked reduction in acute normal tissue toxicity while maintaining full target coverage. PRESTO builds on these findings by advancing both the underlying science and the technology needed for clinical translation.

The project focuses on four main challenges:

●     In vivo studies – Provide preclinical evidence that pMBRT spares normal tissues without compromising tumour control and demonstrate the absence of increased severe toxicities.

●     Treatment Planning – Implement new mathematical models, select and validate (new) parameters and quantities incorporated into a dedicated PRESTO-TPS for pMBRT. Use these to design preclinical scenarios and to develop and evaluate treatment planning protocols using retrospective neurological and head-and-neck cases.

●     Modelling – Develop hypothesis-based mathematical models to describe and predict minibeam effects, apply them to experimental data to identify limitations and gain mechanistic insight, and provide the models for implementation in PRESTO-TPS.

●     Beam Modifier Development – Design and evaluate 2D range modulators and slit/hole collimators, establish traceable and accurate dosimetric protocols for pMBRT, assess out-of-field dose and safety, and define guidelines for a clinically applicable pMBRT delivery system.

By integrating biology, physics, and technology development, PRESTO aims to provide the scientific and technical foundation for the first clinical studies of pMBRT. The long-term goal is to make proton therapy safer and more effective improving outcomes and quality of life for cancer patients.

 

Project coordinator

Prof. Niels Bassler
Aarhus University / Danish Centre for Particle Therapy - AU/DCPT (Denmark)
Department of Clinical Medicine

Deliverables

D9.236	PRESTO - Proton therapy enhancement by spatially fractionated treatment optimization	R-Document, report
D9.238	PRESTO - Project webpage	R-Document, report

Stay up to date with PRESTO by following us on LinkedIn, Bluesky, and Mastodon.