Reducing the dose delivered to major intracranial blood vessels in brain radiotherapy using spot-scanning proton arc therapy.

BACKGROUND: Glioblastoma (GBM) patients have poor clinical prognoses, which may partially be explainable by correlations between radiation-induced killing of circulating blood cells (CBCs) and worse clinical outcomes. Proton radiotherapy is currently delivered via intensity-modulated proton therapy (IMPT), for which the target is irradiated from a few different angles. Spot-scanning proton arc therapy (SPArc), for which the target is irradiated from arc trajectories, is associated with dosimetric benefits, and the first SPArc treatments of head-and-neck cancer patients have now been reported. However, since SPArc increases the low-dose bath, concerns have been raised about potentially higher killing of CBC. PURPOSE: This study aims to evaluate and compare blood vessel dose and dose-averaged linear energy transfer (LETd) distributions between IMPT and SPArc, with and without blood vessel sparing, in patients with GBM. METHODS: For 10 GBM patients, patient-specific cerebrovasculature models were developed, and IMPT and SPArc treatment plans were created according to current clinical standards (IMPTConv and SPArcConv) and with sparing of delineated blood vessels (IMPTSparing and SPArcSparing) for every patient. Dose and LETd distributions were then compared across all treatment plans. RESULTS: While treatment plans maintained comparable target coverage, blood vessel sparing significantly reduced the mean dose to delineated blood vessels, with values of 6.5 ± 2.9 Gy(RBE) for IMPTConv, 5.3 ± 2.3 Gy(RBE) for IMPTSparing, 5.6 ± 2.2 Gy(RBE) for SPArcConv, and 3.8 ± 1.6 Gy(RBE) for SPArcSparing. The dose within the 10% of blood vessel volume receiving the highest dose (D10%) was 29.5 ± 13.4 Gy(RBE) for IMPTConv, 23.2 ± 11.0 Gy(RBE) for IMPTSparing, 24.5 ± 12.6 Gy(RBE) for SPArcConv, and 13.4 ± 8.7 Gy(RBE) for SPArcSparing. CONCLUSIONS: Implementation of blood vessel sparing resulted in successful reductions in blood vessel dose metrics while preserving target coverage, and SPArc further reduced blood vessel dose metrics compared with IMPT, with the potential to reduce radiation-induced lymphopenia and improve clinical outcomes.