Proton pencil beam scanning ultra‐high dose rate 3D lattice radiotherapy: A proof‐of‐concept FLASH SFRT study

BACKGROUND: 3D lattice radiation therapy (3D-LRT) is an effective treatment solution that can offer excellent local tumor control with limited morbidity. Pencil beam scanning (PBS) proton therapy achieves excellent dose conformity and eliminates exit doses to normal tissue, making it a great candidate to implement 3D-LRT. But it may also introduce high entrance doses to normal tissues. Ultra-high dose rate (UHDR) beams may offset this disadvantage by triggering the FLASH normal tissue protection effect. PURPOSE: We conducted the first-ever feasibility study of applying proton PBS UHDR beams to 3D-LRT. This study aims to evaluate the dosimetric feasibility and potential benefits of integrating ultra-high dose rate proton beams with spatially fractionated lattice treatment techniques. METHODS: Two-field and single-field approaches targeting individual vertex were developed to achieve proton PBS UHDR 3D-LRT, in combination to conventional intensity-modulated proton therapy (IMPT) that targets the entire gross tumor volume (GTV). In a two-field technique, beam-modifying devices, including a universal range shifter and beam-specific range compensator, were used to implement distal edge tracking (DET) of single-energy Bragg peak beams to achieve conformal dose to the target volume. Apertures were employed to sharpen the lateral dose fall-off and enhance the peak-to-valley dose ratio (PVDR) for effective 3D-LRT. In a single-field technique, a universal ridge filter was added upstream to broaden Bragg peak beams for uniform and conformal vertex coverage. 3D-LRT treatment plans were designed following published guidelines and evaluated in nine diverse representative cases of three treatment sites: head and neck (H&N), liver, and lung. The prescription dose was 18 GyRBE to vertices and 3 GyRBE to the GTV. These were assessed in terms of nominal plan quality, UHDR coverage to normal tissues, and plan robustness. End-to-end validation was performed on a head-and-neck phantom; dose and dose rate were measured with EBT-XD radiochromic films and a GRID ionization-chamber array and compared against the treatment plan. RESULTS: The two-field technique achieved an average PVDR1 (D2%/D50%) and PVDR2 (D10%/D90%) of 4.4 ± 0.4 and 4.2 ± 0.2, compared to 4.9 ± 0.6 and 4.7 ± 0.3 with the single-field technique. Vertex D90% was higher in the two-field plans (19.7 ± 0.5 GyRBE) than in the single-field plans (19.2 ± 0.6 GyRBE). The two-field technique significantly reduced skin doses, with a D1cc of 9.2 ± 0.9 GyRBE vs. 15.1 ± 0.5 GyRBE in the single-field technique. Both techniques achieved high UHDR coverage, with an average V40GyRBE/s to the skin of 100% for both two-field plans and single-field plans, for doses above 5 GyRBE. Relatively small differences in plan robustness were observed regarding PVDR, D90%, and skin D1cc between the two techniques. End-to-end study achieved consistent dose distribution between measurements and plans with gamma passing rates between 93.4% and 96.7% for two-field and single-field approaches, respectively. The measured dose-rate exceeded 40GyRBE/s for both single-field and two-field plans with average error of 5% compared to plans. CONCLUSION: Proton PBS UHDR 3D-LRT is achievable with the proposed two-field and single-field techniques, leveraging advanced inverse treatment planning and beam modifiers such as universal range shifters, beam-specific range compensators, apertures, and ridge filters. Planning study and end-to-end validation demonstrated that both techniques provided UHDR coverage to entrance normal tissues, favorable for triggering the FLASH effect, while maintaining high PVDR and plan robustness.