Dose-LET Volume Histogram Markers of Genitourinary Toxicity In Proton Prostate SBRT
Abstract
Purpose
Proton prostate SBRT is characterized by steep dose gradients and elevated linear energy transfer (LET) near the end of range, which may contribute to genitourinary (GU) toxicity. Prior work suggests that bladder neck (trigone) dose is a stronger predictor of GU toxicity than whole-bladder dose. This study evaluates dose–LET volume histogram (DLVH) metrics of the bladder and trigone associated with patient-reported GU toxicity in a contemporary proton SBRT cohort.
Methods
Forty-three patients treated with proton SBRT (36.25–40 Gy in 5 fractions) between 2020-2022 were retrospectively analyzed. All plans used two opposed lateral and two anterior oblique beams, delivering 70% and 30% of prescription, respectively. GU toxicity was defined as a minimal clinically important decline in patient-reported GU quality-of-life using the IPSS and EPIC-CP scores, assessed at 3–6-month intervals within 12 months following treatment. The trigone was retrospectively contoured on the planning CT. Bladder and trigone DLVHs were generated, and relative volumes above dose (10–40 Gy) and LET (0.0–5.0 keV/µm) thresholds were compared between patients with and without GU toxicity using the independent Mann–Whitney U test.
Results
Fourteen patients experienced GU quality-of-life decline within 12 months. For the bladder, significant differences (p<0.05) were consistently observed at elevated LET values (approximately 2.6–3.8 keV/µm) across a broad range of dose thresholds. In contrast, significant differences for the trigone were primarily confined to high-dose regions (approximately 35–37 Gy) across a wide range of LET thresholds. Whole-bladder dose metrics demonstrated less consistent association with GU toxicity than trigone dose metrics.
Conclusion
Patient-reported GU toxicity following proton SBRT was most consistently associated with elevated bladder LET and with high-dose exposure of the trigone. These findings suggest that trigone dose and bladder LET may serve as important markers of GU toxicity risk and may be considered during treatment planning for proton SBRT