Proton minibeam radiotherapy (pMBRT), an experimental cancer treatment that delivers spatially modulated doses through arrays of narrow proton beams, may lose part of its tissue-sparing advantage when patients move during treatment, according to new dose calculations from researchers at Institut Curie in France.
The team developed a Monte Carlo-based framework to reconstruct four-dimensional dose distributions for realistic clinical scenarios, then used it to quantify how respiratory motion and small head translations affect the treatment's characteristic alternating pattern of high and low dose. Their findings appear in Physics in Medicine & Biology.
pMBRT uses a multi-slit collimator to create beams typically 0.3 to 1 mm wide, spaced 2 to 6 mm apart. The beams produce alternating peaks and valleys of dose that converge to a homogeneous distribution within the tumour, while the heterogeneous pattern in surrounding tissue is believed to drive the technique's biological sparing effect. Because the collimator blocks much of the proton beam, treatments take longer than conventional radiotherapy, increasing the chance that organ motion will blur the intended dose pattern.
«Given the longer irradiation times, possible patient movement could deteriorate the heterogeneous spatial dose distribution of pMBRT,» said senior author Ludovic De Marzi. «This is all the more problematic because it is this heterogeneous distribution that is believed to be responsible for the technique's biological sparing effect.»
The workflow combines a 4D CT dataset capturing the patient's anatomy and breathing motion over one respiratory cycle with a proton pencil-beam scanning treatment plan created on a reference CT. To validate the tool, the researchers irradiated a thoracic motion phantom with a conventional plan and compared measured and simulated doses. For a 3%/3 mm gamma index, a standard quality check, the mean pass rate across nine irradiations was 97.3%, confirming the calculation performs reasonably well for 4D dose modelling.
Applying the framework to a thoracic treatment with 20 mm breathing motion, the team compared three scenarios: static 3D pMBRT, 4D pMBRT with respiratory motion, and a high-dose-rate 4D scheme in which the instantaneous dose rate was increased tenfold to shorten beam-on time. Motion introduced significant variations in the peak-and-valley pattern, reducing the peak-to-valley dose ratio (PVDR) at 5 mm depth from 11.9 in the static case to 6.7 with motion. The high-dose-rate scheme only slightly mitigated this degradation.
Breathing motion also compromised tumour coverage. The mean target dose fell by 30% and D95%, the minimum dose received by 95% of the target volume, dropped by 35% in the 4D scenarios. Nearby organs at risk were affected as well, with decreased dose to the stomach and a significant increase in mean dose to the spleen.
For an intracranial treatment, where the head undergoes small rigid translations typically limited to less than 1 mm by thermoplastic masks, the team modelled continuous shifts of 1 or 2 mm. These movements did not significantly affect mean dose or D95% for the target or organs at risk. However, even a 1 mm shift degraded the peak–valley pattern, reducing mean PVDR by 10% at 15 mm depth compared with the static case; a 2 mm shift produced a 24% reduction.
The researchers conclude that their 4D dose reconstruction workflow offers a practical tool for assessing interplay effects during pMBRT. Without a specific motion management strategy, only intracranial treatment with movements below 1 mm proved robust to these effects. The same approach could help estimate the sparing effect of pMBRT while accounting for patient motion and adapting treatment plans accordingly.
Looking ahead, the team notes that combining pMBRT with ultrahigh-dose-rate FLASH delivery could shorten treatment times and add a further healthy-tissue sparing effect. «This idea is appealing because it could both solve the problem of reduced dose rate in pMBRT and add an additional biological effect (FLASH) to further spare healthy tissue,» De Marzi said. «However, its feasibility remains to be demonstrated, as does the value of developing a technique that combines such considerable complexities. A simple increase in dose rate – without going as far as FLASH – would already be of interest.»
