Integration of Dose Surface Maps and Genetic Data Identifies the Lower Posterior Rectum as a Key Region for Toxicity...

Area of Science:

• Radiation oncology
• Genomics
• Medical physics

Background:

• Genome-wide association studies (GWAS) identify SNPs linked to rectal toxicity post-prostate cancer radiotherapy.
• Traditional GWAS often overlook radiotherapy dose distribution, a critical factor in toxicity.
• Integrating dose distribution with genetic data can refine understanding of toxicity mechanisms.

Purpose of the Study:

• To combine rectal dose surface maps with genetic data to identify specific rectal regions where genetic variants influence radiotherapy dose-toxicity relationships.
• To investigate genotype-specific rectal toxicity patterns in prostate cancer patients undergoing radiotherapy.

Main Methods:

• Analysis of data from 1,293 prostate cancer patients (REQUITE study).
• Standardized 2D dose surface maps generated using deep learning rectum contouring.
• Voxel-wise Cox proportional hazards models with permutation testing to assess dose-toxicity associations for three candidate SNPs (rs1801516, rs17055178, rs17630638).
• Propensity score matching used to control for confounding factors.

Main Results:

• Significant dose-toxicity associations (P < 0.05) found in risk allele carriers for all SNPs concerning bowel urgency, primarily in the lower posterior rectum.
• Carriers of the risk allele for rs17630638 showed increased risk for acute bowel incontinence and late rectal bleeding, but reduced risk for acute rectal bleeding.
• Spatial mapping revealed genotype-driven toxicity patterns and identified consistent high-risk rectal regions.

Conclusions:

• Spatial dose mapping combined with genetic data successfully identified genotype-driven rectal toxicity patterns.
• The findings strengthen the link between genomics and radiotherapy planning, highlighting specific high-risk rectal regions.
• This approach enables personalized radiotherapy by allowing dose reduction in genetically sensitive patients.