Predictors of Radiotherapy-Related GI Toxicity from Anal Cancer DP-IMRT: Secondary Analysis of RTOG 0529

Radiation Therapy Oncology Group (RTOG) 0529 assessed the feasibility of dose-painted intensity-modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5-FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient (pt) and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel (SB), loosely contoured anterior pelvic contents (APC), and uninvolved portions of colon outside the clinical target volume (UC). T-tests were performed to evaluate differences in the mean absolute volumes of each critical structure receiving doses ≥ 5 to 60 Gy (V5-V60) in 5 Gy increments between pts with and without ≥ grade (G) 2, acute and late GI AEs, and ≥ G3 acute GI AEs using the NCI Common Terminology Criteria, version 3. Differences in mean dose to SB and APC were also evaluated for acute and late ≥ G2 and ≥ G3 GI AEs. Acute is defined as ≤ 90 days from the start of treatment and late is > 90 days. Additional factors (age, location, gender, race, Zubrod, grade, size, stage, prone vs. supine position) were evaluated in multivariate (MV) logistic regression (acute AEs) or Cox proportional hazards models (late AEs) to evaluate correlation with GI AEs. Among 52 evaluable pts, ≥ G2 acute, ≥ G2 late, and ≥ G3 acute GI AEs were observed in 35, 17, and 10 pts, respectively. Trends (p < 0.05) toward statistically significant associations were observed between: ≥ G2 acute GI AEs and SB dose (V20-V40); ≥ creasing age, tumor size > 4 cm, and worse Zubrod. SB and APC dose parameters remained correlated with GI AEs on MV analysis. Treatment in the prone vs. supine position correlated with lower SB V10-V35 and APC V5-V20, although no significant differences in GI AEs were observed. Acute and late GI AEs from 5-FU/MMC chemoradiation using DP-IMRT correlates with RT dose to the SB and APC. Further analysis is underway to determine critical structure cut-point parameters that may aid treatment plan optimization for anal cancer DP-IMRT.