Dosimetry and Gastrointestinal Toxicity Relationships in a Phase II Trial of Pelvic Lymph Node Radiotherapy in...

Pelvic lymph node (PLN) radiotherapy for high-risk prostate cancer is limited by late gastrointestinal toxicity. Application of rectal and bowel constraints may reduce risks of side-effects. We evaluated associations between intensity-modulated radiotherapy (IMRT) dose-volume data and long-term gastrointestinal toxicity.

Data from a single-centre dose-escalation trial of PLN-IMRT were analysed, including conventionally fractionated (CFRT) and hypofractionated (HFRT) radiotherapy schedules. Associations between volumes of rectum and bowel receiving specified doses and clinician- and patient-reported toxicity outcomes were investigated independently. A metric, δ median (δM), was defined as the difference in the medians of a volume between groups with and without toxicity at a specified dose and was used to test for statistically significant differences.

Constraints were respected in most patients and, when exceeded, led to higher rates of gastrointestinal toxicity. Biologically relevant associations between rectum dose-points and toxicity were more numerous with both mild and moderate toxicity thresholds, but statistical significance was limited after correction for false discovery rate. Rectal V50Gy (CFRT) associated with grade 2+ bleeding; bowel V43Gy and V47 (HFRT/4 days/week schedule) associated with patient-reported loose stools and diarrhoea, respectively. Further investigation showed that CFRT patients with rectal bleeding had a mean rectal V50Gy above the treatment planning constraint.

When dose-volume parameters are kept below tight constraints, toxicity is low. Residual dosimetry loses much of its predictive power for gastrointestinal toxicity in the setting of PLN-IMRT for prostate cancer. We have benchmarked dose-volume constraints for safely delivering PLN-IMRT using CFRT or HFRT.