title: Dose to the bladder neck is the most important predictor for acute and late toxicity after low-dose-rate prostate brachytherapy: implications for establishing new dose constraints for treatment planning.
abstract: OBJECTIVE
  To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT).
  
  
  METHODS
  From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC).
  
  
  RESULTS
  Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001).
  
  
  CONCLUSIONS
  Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Lara
authors.initials: L
authors.lastname: Hathout
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Folkert
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Marisa A
authors.initials: MA
authors.lastname: Kollmeier
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Gil'ad N
authors.initials: GN
authors.lastname: Cohen
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: zelefskm@mskcc.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010165:Palladium / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D012372:ROC Curve; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D001743:Urinary Bladder / Q000528:radiation effects*; D014555:Urination Disorders / Q000209:etiology
chemical_list: D007457:Iodine Radioisotopes; D010165:Palladium