Nawaid Usmani1, Nelson Leong2, Kevin Martell2, Lanna Lan2, Sunita Ghosh3, Nadeem Pervez4, John Pedersen4, Don Yee4, Albert Murtha4, John Amanie4, Ron Sloboda5, David Murray3, Matthew Parliament4. 1. Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: Nawaid.Usmani@albertahealthservices.ca. 2. Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada. 3. Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; Division of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada. 4. Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. 5. Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; Division of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada.
Abstract
PURPOSE: To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a (125)I prostate brachytherapy implant. METHODS AND MATERIALS: Genomic DNA from 296 men treated with (125)I prostate brachytherapy monotherapy was extracted from saliva samples for this study. A retrospective database was compiled including clinical, dosimetric, and toxicity data for this cohort of patients. Fourteen candidate single-nucleotide polymorphism (SNPs) from 13 genes (TP53, ERCC2, GSTP1, NOS, TGFβ1, MSH6, RAD51, ATM, LIG4, XRCC1, XRCC3, GSTA1, and SOD2) were tested in this cohort for correlations with toxicity. RESULTS: This study identified 217 men with at least 2 years of followup. Of these, 39 patients developed Grade ≥2 late urinary complications with a transurethral resection of prostate, urethral stricture, gross hematuria, or a sustained increase in their International Prostate Symptom Score. The only clinical or dosimetric factor that was associated with late urinary toxicity was age (p = 0.02). None of the 14 SNPs tested in this study were associated with late urinary toxicity in the univariate analysis. CONCLUSIONS: This study identified age as the only variable being associated with late urinary toxicity. However, the small sample size and the candidate gene approach used in this study mean that further investigations are essential. Genome-wide association studies are emerging as the preferred approach for future radiogenomic studies to overcome the limitations from a candidate gene approach. Crown
PURPOSE: To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a (125)I prostate brachytherapy implant. METHODS AND MATERIALS: Genomic DNA from 296 men treated with (125)I prostate brachytherapy monotherapy was extracted from saliva samples for this study. A retrospective database was compiled including clinical, dosimetric, and toxicity data for this cohort of patients. Fourteen candidate single-nucleotide polymorphism (SNPs) from 13 genes (TP53, ERCC2, GSTP1, NOS, TGFβ1, MSH6, RAD51, ATM, LIG4, XRCC1, XRCC3, GSTA1, and SOD2) were tested in this cohort for correlations with toxicity. RESULTS: This study identified 217 men with at least 2 years of followup. Of these, 39 patients developed Grade ≥2 late urinary complications with a transurethral resection of prostate, urethral stricture, gross hematuria, or a sustained increase in their International Prostate Symptom Score. The only clinical or dosimetric factor that was associated with late urinary toxicity was age (p = 0.02). None of the 14 SNPs tested in this study were associated with late urinary toxicity in the univariate analysis. CONCLUSIONS: This study identified age as the only variable being associated with late urinary toxicity. However, the small sample size and the candidate gene approach used in this study mean that further investigations are essential. Genome-wide association studies are emerging as the preferred approach for future radiogenomic studies to overcome the limitations from a candidate gene approach. Crown