Phase 1 Study of Online Proton Adaptive RadioTherapY (PARTY)

Proton stereotactic body radiotherapy (SBRT) offers advantageous dosimetric properties but is highly sensitive to setup variation, anatomic change, and range uncertainty, limiting broader clinical adoption. Online adaptation of proton therapy has the potential to address these limitations. This report presents the results of a Phase Iprospective clinical trial evaluating the feasibility, safety, and dosimetric impact of online adaptive proton SBRT.

Ten patients with oligometastatic malignancies involving abdominal, pelvic, or thoracic sites were enrolled. All patients underwent online adaptive proton SBRT using an inroom CT-on-rails-guided workflow. Prescribed doses ranged from 30-50 CGE delivered in five fractions. The primary endpoint was feasibility, defined as successful completion of the online adaptive workflow and treatment delivery in ≥70% of fractions. Dosimetric outcomes, treatment times, toxicity, and the impact of intrafraction motion were prospectively assessed.

All patients completed planned treatment, and feasibility was achieved in 100% of fractions (50/50). Median door-to-door treatment time was 88 minutes. Online adaptation was required in 84% (42/50) of fractions: 48% (20/42) of fractions were adapted to resolve organ-at-risk (OAR) dose constraint violations, 38% (16/42) of fractions were adapted due to improved target coverage and 14% (6/42) of the fractions were adapted for both indications. Adapted plans demonstrated statistically significantly improved target coverage and reduced OAR dose compared with nonadaptive plans, with benefits persisting after accounting for intrafraction motion. Treatment was well tolerated, with one Grade 3 toxicity of unclear attribution and no other high-grade toxicities. After a median follow-up of 7.8 months, local control at 3 months was 90% and 73% at 6 months; overall survival was 90% and 75% at 3 and 6 months.

This prospective clinical trial demonstrates the feasibility and dosimetric value of endto-end online adaptive proton SBRT. Online adaptation enabled safe delivery of ablative proton doses despite daily anatomic variation and motion, supporting broader clinical application of proton SBRT and future refinement of adaptive proton therapy workflows.