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A combined dose and microdosimetric modeling framework incorporating volume effects correlates with tissue sparing in proton minibeam radiotherapy

In brief

Proton minibeam predicts substantial normal tissue sparing when peak-to-valley ratio exceeds 15

A new dose-microdosimetric model showed that proton minibeam radiotherapy lowers normal tissue complication probability compared with conventional homogeneous fields, especially when the peak-to-valley dose ratio is greater than 15 and organ seriality is around 0.7. The effect is strongest at shallow depths and aligns with prior experimental trends, suggesting that incorporating microdosimetry and tissue architecture could guide future clinical optimization.

Journal
International journal of radiation oncology, biology, physics (Q1)
Published
13 September 2026
Study design
Unclassified
Evidence level
Level 5, Expert Opinion (CEBM 5)
Authors
G Bordieri, M Missiaggia, M Battestini, G Lattanzi, F Romano, E Scifoni, et al.
PMID
42732793
DOI
10.1016/j.ijrobp.2026.09.007

Why clinicians should know about it

  • Picked for Medical Physics (paper of the day, 17 September 2026): Monte Carlo microdosimetry of proton minibeams

Abstract

PURPOSE: Proton minibeam (pMB) radiotherapy, delivers highly heterogeneous dose distributions alternating high-dose peaks and low-dose valleys. This aims to widen the therapeutic window by improving normal tissue sparing while maintaining the same or even better tumour control. The performance of pMB strongly depends on the collimator design and physical parameters. To better understand the physical and radiobiological drivers of this enhanced therapeutic window, we perform a detailed microdosimetric characterization of proton minibeams and assess their impact. METHODS: We characterize radiation quality with microdosimetry through Monte Carlo simulations. Then we extend the XXX model to predict the normal tissue complication probability (NTCP) at different depths in water, 1cm, 2cm, and 4cm, for 100MeV proton minibeams realized with varying configurations of collimator. Results are compared with conventional homogeneous field (HF) irradiation after dose normalization to the tumor. The developed model is applied by considering tissues as divided into several functional subunits, connected by introducing a seriality parameter. RESULTS: Microdosimetric characterization of proton minibeam irradiation shows differences between peak and valley regions in shaping lineal energy spectra, especially at low depth, while radiation quality uniforms progressively getting closer to the target region (tumor). NTCP calculations results suggest an increased sparing effect for pMB over conventional HF. A strong dependence is found on the peak-to-valley dose ratio (PVDR), and on the seriality parameter. Predictions indicate substantial sparing from pMB, especially for PVDR>15, including relatively serial organs with seriality around 0.7. All results are consistent with the general trends reported in experimental studies. CONCLUSION: This integrated dose-microdosimetric-biological framework elucidates how spatial fractionation, radiation quality, and organ architecture collectively shape tissue sparing in pMB. The findings identify conditions under which pMB may offer NTCP reduction, highlighting the importance of incorporating microdosimetry and tissue seriality in future optimization and clinical translation efforts.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.