Impact of Organ-at-Risk (OAR) Radiation Dosimetry on Acute and Late Toxicity after Prostate Stereotactic Body Radiation Therapy (SBRT): A Post-Hoc Analysis of a Phase III Randomized Clinical Trial of MRI-Guided vs. CT-Guided SBRT.

A recent phase III clinical trial at a single institute has demonstrated that aggressive margin reduction with MRI-guided prostate SBRT decreased acute grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicity following prostate SBRT, as compared against CT-guidance. We hypothesized that toxicity reduction could be attributable to decreased radiation exposure to nearby urinary and bowel structures. Herein, we evaluate the dosimetric impact of margin reduction on relevant GU and GI organs-at-risk (OARs) and its association with GU and GI toxicity. One-hundred-and-fifty-six patients were randomized to CT-guided (4 mm PTV-expansion) or MR-guided (2 mm PTV-expansion) prostate SBRT (40 Gy in 5 fractions). Dosimetric statistics (D0.035cc, V40Gy, V39Gy, V20Gy) for relevant OARs (bladder, rectum, and small bowel) were calculated on pre-treatment simulation images. Physician-scored acute (0-3 months) and late (>3-24 months) GU and GI toxicity (CTCAE v4.03 scale) were evaluated. Statistical significance was assessed using two-sided, unpaired t-tests with level of significance set at 0.05. High dose radiation to the bladder was significantly decreased with MRI-guided treatment compared to CT-guided treatment (D0.035cc, V40Gy and V39Gy, p < 0.05). Rectal dosimetry was comparable between treatments regardless of hydrogel placement. Radiation to the small bowel (D0.035cc) trended lower in the MRI-guided treatment arm, but differences did not reach statistical significance. Regardless of treatment arm, bladder dose was higher in patients with acute (V20Gy, V39Gy, V40Gy, p<0.05) and late (V40Gy, p<0.05) grade ≥ 2 GU toxicity. Rectal dose trended higher in patients with acute and late grade ≥ 2 GI toxicity but failed to reach statistical significance. Small bowel dose was higher in patients with acute grade ≥ 2 GI toxicity (D0.035cc and V20Gy, p<0.05) and trended higher in those with late grade ≥ 2 GI toxicity. Aggressive margin reduction results in significantly lower dose to the bladder, and regardless of margin, higher bladder doses were associated with acute and late toxicity. A similar, though less marked, association was seen for small bowel dosimetry. In contrast, rectal dosimetry was not significantly different between arms, though increased rectal dose trended towards association with acute and late toxicity. These results suggest that while margin reduction might explain the significant differences in GU toxicity, dosimetry alone may not account for the large differences seen in GI toxicity. Limitations include analysis of discrete dosimetric parameters and planned dose. [ABSTRACT FROM AUTHOR]

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