Interim Analysis of Pro-Grid: A Phase 1 Proton Spatially Fractionated Radiation Therapy Trial.

Purpose: Spatial fractionation (SFRT) is a radiation therapy technique that targets bulky tumors by delivering alternating high and low doses within the tumor. Here, we report an interim analysis of a phase 1 trial examining the feasibility and safety of a novel proton SFRT approach. Methods and Materials: Ten patients with unresectable tumors of varying histopathology measuring at least 7 cm in the palliative setting were enrolled in a prospective phase 1 trial. Robust pencil-beam scanning proton SFRT plans were created using cylindrical (grid) targets within gross tumor treated to a prescription dose of 18 Gy in a single fraction. Quality assurance computed tomography imaging (qCT) was performed before treatment delivery. Results: Four patients had breast primaries, 3 patients had lung primaries, and 3 patients had pelvic primaries. Five patients had prior photon treatment to a different site. Eight patients received additional planned normofractionated radiation therapy totaling an average dose of 30 Gy. Median time from SFRT treatment to last follow-up was 25 weeks (range, 4-60 weeks). Gross tumor volume ranged from 151 cm³ to 1638 cm³. All qCTs maintained robustness, with no re-planning needed. At last follow-up, 40% showed partial response, 20% had stable disease, and 40% experienced disease progression, with half progressing in the treated area. One patient with pelvic treatment developed grade 3 small bowel obstruction, followed by late grade 2 obstructions. No other patients had grade 3 or higher acute or late toxicities attributable to the proton SFRT. Conclusions: Spatial fractionation using a novel pencil-beam scanning SFRT technique was technically feasible to deliver and reliable on robust evaluation of qCT in this small prospective cohort of patients with difficult-to-manage bulky tumors. Proton SFRT appears safe even when additional normofractionated radiation therapy is delivered. Some bulky tumors exhibited significant response to proton SFRT; thus, further work elucidating which patients most benefit from this technique is warranted.