UCSF

PURPOSE: The MIRAGE (Magnetic resonance imaging-guided versus computed tomography-guided stereotactic body radiotherapy for prostate cancer) trial (NCT04384770) showed that aggressive planning target volume (PTV) margin reduction, achieved by leveraging the advanced image-guidance of magnetic resonance imaging guided radiation therapy, led to lower toxicity after stereotactic body radiation therapy (SBRT) to the prostate compared with computed tomography guided SBRT (CTgSBRT) with a standard PTV margin. It is unknown whether the dosimetric benefit of reducing PTV margins alone-independent of the other components of advanced image guided radiation therapy that allowed margin reduction-would be predicted to replicate this decrease in toxicity. METHODS AND MATERIALS: We retrospectively replanned 16 CTgSBRT patients with 3- and 2-mm PTV margins from the 4 mm used in MIRAGE to compare with magnetic resonance imaging guided SBRT (MRgSBRT) patients' radiation therapy plans (n = 79), which used a 2-mm PTV margin. We compared target and organs-at-risk dosimetry and performed multivariable linear regression to control for potentially related covariates. We estimated normal tissue complication probability to assess the potential impact of PTV margin reduction on the risks of rectal and bladder toxicity. RESULTS: Compared with MRgSBRT patients, replanned CTgSBRT patients had similar (3 mm) or statistically significantly improved (2 mm) rectal dosimetry and similar bladder dosimetry (2 mm). These trends persisted on multivariable linear regression. Normal tissue complication probability modeling demonstrated a statistically significant improvement in rectal toxicity whereby margin reduction from 4→3 mm and 4→2 mm resulted in relative reductions in toxicity probabilities of 56% and 78%, respectively. For bladder toxicity, reducing margins from 4 to 3 or 2 mm reduced the probability of bladder toxicity by 96%, although these relative differences were not statistically significantly. CONCLUSIONS: Reducing PTV margins for CTgSBRT plans produced similar to improved organs-at-risk dosimetry compared with the clinical MRgSBRT plans, which in turn would be predicted to reduce toxicity when compared to larger margin CTgSBRT plans. This improvement in dosimetry could explain the reduction in modeled rectal toxicity, but the impact on bladder toxicity is unclear, with large, but nonsignificant relative differences underscoring our incomplete understanding of the drivers of post-SBRT urinary toxicity.