Integration of dose surface maps and genetic data identifies the lower posterior rectum as a key region for toxicity after prostate cancer radiotherapy.
Academic Article
Overview
abstract
PURPOSE: Genome-wide association studies (GWAS) are the gold standard for identifying single-nucleotide polymorphisms (SNPs) associated with rectal toxicity after prostate cancer radiotherapy. However, they often neglect the radiotherapy dose distribution, which is a key contributor to toxicity risk. Here we combined rectal dose surface maps with genetic data to identify rectal regions where variants influence dose-toxicity relationships. EXPERIMENTAL DESIGN: Data was analysed from 1,293 prostate cancer patients from the REQUITE study. Deep learning rectum contouring ensured consistent segmentation and rectum lengths were standardised to generate 2D dose surface maps. Patients were categorized based on the presence of risk alleles for three candidate SNPs (rs1801516, rs17055178, rs17630638). Propensity score matching accounted for age, rectal volume, prostate volume, and hormone therapy. Voxel-wise Cox Proportional Hazards Models (CPHM) with permutation testing assessed dose-toxicity associations. RESULTS: Voxel-wise CPHM revealed significant (p < 0.05) dose-toxicity associations in risk allele carriers for all SNPs for bowel urgency. Risk regions were consistently in the lower posterior rectum. Higher risk of acute bowel control was identified among carriers of the risk allele for rs17630638. For this SNP, carriers of the risk allele showed higher risk for and late rectal bleeding, but reduced risk for acute rectal bleeding. CONCLUSIONS: This study identified genotype-driven toxicity patterns using spatial dose mapping. By revealing consistent high-risk rectal regions, this approach strengthens the link between genomics and radiotherapy planning. Importantly, modern radiotherapy planning makes it feasible to reduce dose in genetically sensitive patients and move toward more personalised treatment.
