Carbon-Ion Spatially Fractionated Radiotherapy: 3D Lattice-Vertex Optimization to Amplify High-LET Dose Peaks and Biological Efficacy
Abstract
Purpose
We compared carbon-ion vs. photon lattices spatially fractionated radiotherapy on identical tumor geometries and developed a 3D vertex-optimization that steers high- linear energy transfer (LET) spots into pre-defined peaks to maximize biological gain without compromising normal-tissue sparing.
Methods
Twelve patients were planned with 20 Gy single-fraction to gross tumor volume (GTV). Three plans were generated for each case: photon lattice, standard carbon-ion lattice, and carbon-ion lattice with vertex-optimized spot placement. Plan quality metrics included peak-to-valley dose ratios (PVDR1) (D10/D90 of GTV) and PVDR2 (mean lattice dose / mean non-lattice GTV dose), organs-at-risk (OAR) doses, and LET indicators within lattice peaks: minimum LETd and volumes receiving LETd > 40, 60, 80 and 100 keV·µm⁻¹. Two-tailed paired t-tests were used for statistical comparison.
Results
Under identical lattice vertex configurations, carbon-ion plans exhibited significantly higher peak-to-valley dose ratios than photon plans (PVDR1: 232.31 ± 321.62 vs. 10.62 ± 13.10; PVDR2: 5.71 ± 5.96 vs. 2.51 ± 1.60; both p < 0.05). Maximum doses to the OARs were consistently lower with carbon ions (esophagus: 25.45 ± 44.62 cGy vs. 587 ± 296.51 cGy; heart: 249.09 ± 263.61 cGy vs. 614.73 ± 586.2 cGy; skin: 784.82 ± 221.86 cGy vs. 1176.45 ± 552.64 cGy; spinal cord: 17.64 ± 25.61 cGy vs. 510.82 ± 303.9 cGy; all p < 0.05). Vertex optimization preserved these advantages while raising minimum LETd inside peaks from 44.45±10.95 to 52.04±10.33 keV µm⁻¹ and mean LETd from 75.41±7.24 to 79.17±6.6 keV µm⁻¹ (p < 0.05).
Conclusion
Carbon-ion plans significantly increased PVDR and reduced OAR doses relative to photon plans. The vertex-optimized strategy further elevated the minimum and mean LETd inside lattice peaks without degrading PVDRs or increasing normal-tissue exposure, achieving a precise “LET boost” within high-dose sub-volumes. These findings provide both dosimetric and radiobiological rationale for clinical carbon-ion SFRT.