KEY POINTS
- Preclinical radiobiology study comparing clinical pencil beam scanning and double scattering proton delivery in 3 Ewing sarcoma cell lines: A673, MHH-ES-1, and CHLA-10.
- Irradiations were performed on a clinical Proteus 235 isochronous cyclotron capable of both delivery modes, with samples positioned in the plateau and mid-spread-out Bragg peak.
- Monte Carlo simulations showed no meaningful dose or linear energy transfer differences at the sample positions between scanned and scattered delivery.
- Two-dimensional and three-dimensional spheroid survival assays showed no consistent survival difference between delivery modes in either plateau or mid-spread-out Bragg peak conditions.
- Pencil beam scanning showed higher reactive oxygen species production and more residual 53BP1 foci at 18 hours after irradiation, despite similar tumor cell survival.
CLINICAL TAKEAWAY
This study is reassuring for tumor control assumptions: scanned and scattered clinical proton beams showed similar in vitro effectiveness in Ewing sarcoma models. The biological signal is not completely neutral, because scanned delivery produced higher oxidative stress and residual DNA damage markers, but the work remains preclinical. It should not change clinical proton planning today, but it supports further investigation of whether these biological differences matter for normal-tissue effects or late toxicity.