Dose-volume analysis of planned versus accumulated dose as a predictor for late gastrointestinal toxicity in men receiving radiotherapy for high-risk prostate cancer

Abstract

Background and purpose: Significant dose deviations have been reported between planned (D_P) and accumulated (D_A) dose in prostate radiotherapy. This study aimed to develop multivariate analysis (MVA) models associating Grade 1 and 2 gastrointestinal (GI) toxicity with clinical and D_P or D_A dosimetric variables separately.

Materials and methods: Dose volume (DV) metrics were compared between D_A and D_P for 150 high-risk prostate cancer patients. MV models were generated from significant clinical and dosimetric variables (p < 0.05) at univariate level. Dose-based-region of interest (DB-ROI) metrics were included. Model performance was measured, and additional subgroup analysis were performed.

Results: Rectal D_A demonstrated a higher intermediate-high dose (V_{30-65 Gy} and DB-ROI at 15-50 mm) compared to D_P. Conversely, at the very high dose region, rectal D_A (V_{75 Gy} and DB-ROI at 5-10 mm) were significantly lower. In MVA, rectal DB-ROI at 10 mm was predictive for Grade ≥ 1 GI toxicity for D_A and D_P. Age, rectal D_A for D_{0.03 cc}, and rectal D_P for DB-ROI 10 mm were predictors for Grade 2 GI toxicity. Subgroup analysis revealed that patients ≥ 72 years old and a rectal D_A of ≥ 78.2 Gy were highly predictive of Grade 2 GI toxicity.

Conclusions: The dosimetric impact of a higher dose rectal dose in D_A due to volumetric changes was minimal and was not predictive of detrimental clinical toxicity apart from rectal D_{0.03 cc} ≥ 78.2 Gy for Grade 2 GI toxicity. The use of the DB-ROI method can provide equivalent predictive power as the DV method in toxicity prediction.

Keywords: Accumulated dose; Gastrointestinal toxicity; High-risk prostate; Predictive model; Volumetric image-guidance.