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@ARTICLE{Bouzaki:305363,
      author       = {A. Bouzaki and E. Vasquez Osorio and S. Kerns and M. van
                      Herk and A. Morris and J. Shortall and D. Azria and M.-P.
                      Farcy-Jacquet and J. Chang-Claude$^*$ and A. Choudhury and
                      A. Dunning and M. Lambrecht and B. Avuzzi and D. De
                      Ruysscher and P. Seibold$^*$ and E. Sperk and C. Talbot and
                      A. Vega and L. Veldeman and A. Webb and B. Rosenstein and C.
                      West and T. Rancati and E. Gioscio and A. McWilliam},
      title        = {{I}ntegration of dose surface maps and genetic data
                      identifies the lower posterior rectum as a key region for
                      toxicity after prostate cancer radiotherapy.},
      journal      = {Clinical cancer research},
      volume       = {nn},
      issn         = {1078-0432},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2025-02107},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {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.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.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.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.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41081635},
      doi          = {10.1158/1078-0432.CCR-25-2102},
      url          = {https://inrepo02.dkfz.de/record/305363},
}