Microbeam radiotherapy - clinical and dosimetric investigation of a first clinical application

Microbeam Radiotherapy (MRT) is an emerging radiotherapy technique which delivers spatially fractionated beams on a micrometre scale. In preclinical studies MRT has demonstrated superior normal tissue sparing compared to conventional radiotherapy while maintaining tumour control. However, MRT has traditionally been achievable only at large synchrotron facilities which has impeded clinical translation. The development of a compact line-focus X-ray tube (LFXT) provides a pathway for clinical MRT, but identification of clinically and dosimetrically suitable patient scenarios is required for first-in-human trials.

Potentially eligible patients were selected from our patient cohort based on clinical criteria including palliative treatment indication, superficial tumour location, reproducible and safe positioning, minimal interference from other therapies, and expected benefit from MRT. Three-dimensional forward treatment planning was performed in Eclipse using gantry rotations, collimator positioning, and conformal masks to treat the clinical target volume (CTV). Dose was calculated in Eclipse using a custom Monte Carlo-based hybrid algorithm adapted for the compact LFXT system with a 300 kVp beam and an eccentric focal spot. A single-fraction equivalent uniform doses (EUD) of 3 Gy was prescribed to the target volume. Dose distributions were analysed using dose-volume histograms (DVHs), peak and valley depth dose profiles, and peak-to-valley dose ratios (PVDRs).

Selected cases included primary lymphoma, squamous cell carcinoma, and superficial soft tissue metastases. Dosimetric analysis under exploratory assumptions demonstrated dosimetrically feasible treatment plans with optimal target coverage and organ-at-risk (OAR) sparing for gluteal, nuchal, and inguinal tumours. Maximum OAR doses remained below 8.5 Gy, except in bone or overlapping high-density regions. The mean peak and valley dose across all plans was 57.2 Gy and 3.9 Gy, respectively, with a mean PVDR of 15.4. Dose inhomogeneities were observed due to tissue heterogeneity, kilovoltage beam interactions, and a limited range of suitable gantry angles. Tumours in anatomically complex regions, including those in proximity to OARs or tissue inhomogeneities, showed less favourable trade-offs between target coverage and OAR sparing.

This study identifies clinically and dosimetrically suitable scenarios for first-in-human MRT trials, highlighting superficial tumours as optimal initial indications. While peak, valley, and PVDR values align with preclinical evidence, their clinical significance remains uncertain. Careful, safety-driven dose escalation studies will be required to establish a foundation for responsible and effective clinical application of MRT in early-phase clinical trials.