2386 - Promise of LET-Optimized Intensity Modulated and Arc Proton Therapy for Pediatric Rhabdomyosarcoma: A Multi-Patient Comparative Dosimetry Study

Purpose/Objective(s): Local control (LC) of group III parameningeal rhabdomyosarcoma (PM-RMS) is inferior to other primary sites. Efforts to improve LC through radiation dose escalation have been unsuccessful and subject adjacent organs in the brain and skull base to significant risk. This study compares standard volumetric arc photon therapy (VMAT) with intensity modulated proton therapy (IMPT) and proton arc therapy (PAT) plans optimized using biological treatment intensification through linear energy transfer (LET).

Materials/Methods: VMAT, IMPT, and PAT plans were developed using Raystation in 13 pediatric rhabdomyosarcoma patients with a standard prescription dose of 36 GyRBE to clinical target volume (CTV1) and 14.4 GyRBE to CTV2/gross target volume (GTV), for a nominal total dose of 50.4 GyRBE. The proton plans were optimized to deposit high LET (>4 keV/µm) in the gross disease and low LET (~2 keV/µm) in nearby critical structures. The Lyngholm RBE model was used to evaluate RBE-weighted dose distributions across all plans.

Results: The VMAT, IMPT, and PAT plans delivered a similar RBE-weighted mean dose to the body (7.2 ± 2.6, 6.2 ± 2.0 vs 6.5 ± 2.3 GyRBE, respectively) and the brain (5.7 ± 2.5, 4.4± 2.4 vs 4.4 ± 2.1 GyRBE, respectively). IMPT and PAT demonstrated comparable LET and RBE-weighted dose distributions for the 12 critical structures evaluated and all normal tissue constraints were achieved. IMPT and PAT maintained CTV1 target coverage while delivering a biologically enhanced dose to the CTV2 (mean D99/D50 of 58.9/62.1 and 58.9/62.3 GyRBE for IMPT and PAT, respectively). The mean CTV2 D99/D50 for IMPT and PAT were significantly higher than the mean D99/D50 (51.1/52.1 GyRBE) in comparative VMAT plans (Table 1).

Conclusion: LET optimized IMPT and PAT plans can simultaneously maintain target coverage, biologically enhance the dose to gross disease, and keep adjacent normal tissues within tolerance. This novel approach should be explored to improve our current suboptimal LC in children with Group III PM-RMS. Compared to IMPT, PAT might offer the practical advantage of quicker treatment delivery without an increase in mean body or brain radiation exposure.