2182 - Integration of Temporal and Spatial Proton Modulation: Dosimetric Feasibility of Pulsed Dose Rate Spot-Scanning Proton Arc Therapy for Dose Escalated Treatment of Newly Diagnosed Glioblastoma

Purpose/Objective(s): Radiation therapy remains central to glioblastoma (GBM) management, yet delivery approaches have changed little over decades. Recent randomized data (NRG-BN001) demonstrated improved survival with proton-based dose escalation, and temporally modulated pulsed radiation therapy (TMPRT) has shown promising early outcomes. Spot-scanning proton arc therapy (SPArc) is an emerging technique that may improve conformality and normal tissue sparing. This study evaluated the dosimetric feasibility of combining dose-escalated pulsed dose rate proton therapy with SPArc and tested the hypothesis that SPArc would provide superior dosimetric performance compared with conventional multi-field intensity-modulated proton therapy (IMPT).

Materials/Methods: Ten patients with newly diagnosed GBM were retrospectively replanned using conventional multi-field IMPT and SPArc incorporated the spot sparsity optimization algorithm. Both techniques employed robust optimization with identical constraints and incorporated simultaneous integrated boost dose escalation to 75 Gy(RBE) in 30 fractions. Dosimetric endpoints included target coverage (D98%, D95%), conformity index, homogeneity index, integral dose to uninvolved brain, and doses to organs at risk (OAR). Paired comparisons were performed using paired t-tests or Wilcoxon signed-rank tests, with two-sided P<0.05 considered statistically significant.

Results: SPArc improved high-dose target coverage compared with IMPT, with higher CTV75 V75 (P=0.021), while maintaining equivalent elective volume coverage (CTV50 V50, P=1.000). Conformity was numerically improved with SPArc (P=0.074), with similar homogeneity. SPArc reduced uninvolved brain dose, including lower healthy brain D5% (P=0.028). Integral brain dose was reduced with SPArc (37.39 vs 39.08 Gy·L, P=0.227), while maintaining OAR dose constraints. The dosimetric advantages of SPArc were most notable in tumors located near the base of skull and adjacent to OARs, including brainstem and optical apparatus. As an example, in two cases, SPArc improved CTV75 V98 from 86.6% and 74.3% to 98.1% and 96.5%, respectively, while maintaining OAR dose constraints.

Conclusion: Dose-escalated pulsed dose rate SPArc is dosimetrically feasible and provides superior target coverage, improved conformity, and enhanced sparing of uninvolved brain and critical structures compared with conventional IMPT. Notably, in geometrically challenging scenarios, particularly when tumor volumes abut critical structures, SPArc maintains superior target coverage while preserving OAR constraints, highlighting its potential to safely enable dose escalation. These findings support further clinical evaluation of SPArc as an advanced proton delivery platform for dose-escalated treatment of GBM.