Researchers at the Danish Centre for Particle Therapy (DCPT) have achieved promising results in preclinical proton minibeam radiotherapy (pMBRT). The qualitative sparing effect of minibeams has been shown before, but in this study led by Professor Niels Bassler and postdoc Fardous Reaz the team quantified the improvement in the therapeutic window, demonstrating a clear reduction in acute toxicities while maintaining tumour control using an in-house developed collimator.

Published in Radiotherapy & Oncology, the study demonstrates that pMBRT reduces acute toxicities so effectively that the target dose could be escalated by at least a factor of 1.4-1.5 without severe side effects. The custom-developed multislit collimator segments the proton beam into minibeams, enabling precise irradiation while sparing healthy tissue.

In the study, 75 mice underwent localized irradiation of the right hind leg, with skin reactions monitored over 25 days using a standardized scoring system. A separate tumor-bearing cohort allowed the team to establish dose-response relationships within the homogeneous target region, enabling a direct comparison between pMBRT and conventional proton therapy. Notably, no severe acute toxicities were observed in the pMBRT group, even as tumor control remained equivalent to conventional treatment.

“The results show great potential in improving radiotherapy. By obtaining dose-response curves, we have for the first time quantified the widening of the therapeutic window, meaning reducing normal tissue damage without compromising tumor control. I find it astonishing that after decades of proton therapy, there still seem to be substantial gains waiting to be realized and translated to clinical practice.” Says Professor Niels Bassler.

Toward Clinical Translation

These findings suggest promising clinical applications, including safer dose escalation and reduced long-term risks of radiation-induced side effects. The team will further investigate whether the acute sparing effects of pMBRT translate into fewer late effects using the grid factor (GF) metric, a standardized tool introduced in this study to assess efficacy.

- If these results can be transferred to the clinic, we may see a major breakthrough in radiotherapy. We might be able to treat certain types of cancer, for instance large sarcomas that can be difficult to treat today”, says PhD student Fardous Reaz.

However, further preclinical and translational studies are essential to confirm efficacy, optimize treatment parameters, and ensure safety before clinical implementation.

The study in short: Probing the therapeutic window

This study introduces a quantification framework for pMBRT, addressing the complexities of beam arrangement, dose distribution, and spatial fractionation. By focusing on uniform tumor dosing, the researchers provide a systematic method to evaluate the therapeutic window, ensuring that future advancements in pMBRT are built on a quantitative foundation.

Find the publication here: 

Reaz F. et al.: Probing the therapeutic window of proton minibeam radiotherapy using dose-response curves in a mouse model. Radiother Oncol. 2025 Jul 19:211:111050. DOI: 10.1016/j.radonc.2025.111050. Online ahead of print.