title: Improved conformality and decreased toxicity with intraoperative computer-optimized transperineal ultrasound-guided prostate brachytherapy.
abstract: OBJECTIVE
  We have developed an intraoperative three-dimensional (3D) conformal treatment planning system for permanent prostate implantation in an effort to reduce toxicity further and improve the accuracy of this procedure. We report the preliminary outcome of patients with localized prostate cancer treated with this approach.
  
  
  METHODS
  Two hundred forty-eight patients with clinically localized prostate cancer were treated with transperineal ultrasound-guided permanent prostate implantation using a real-time intraoperative 3D conformal technique (I-3D) between 1997 and 2001. A genetic algorithm optimization program intraoperatively evaluated the dose deposited throughout the entire 3D volume for multiple seed configurations to identify which seed-loading pattern adhered best to the predetermined target, urethral and rectal dose constraints. The median follow-up time in these patients was 27 months (range 12-51). The dosimetric outcome and acute toxicity profile of these 248 patients were compared with those of patients who were treated between 1988 and 1996 at our institution with a preplanned transperineal implantation technique (PP).
  
  
  RESULTS
  Postimplantation dosimetric analysis of the I-3D group demonstrated that the median value of the percentage of the target volume treated to at least the prescription dose (V(100)) was 96%, and the target coverage with the prescription dose (PD) was </=90% in only 3% of these patients. In contrast, among patients treated with the PP method, the median V(100) was 88% and the target coverage with the PD was </=90% in 60% of these patients (p < 0.001). For the I-3D patients, the median and maximal dose to the urethra was 140% and 170% of the PD, respectively, compared with 263% and 532%, respectively, for patients treated with the PP technique. The percentage of urinary symptom resolution at 6, 12, 18, and 24 months for the I-3D cohort was 39%, 72%, 90%, and 97%, respectively. In contrast, the percentage of symptom resolution at the same intervals for patients treated with the PP technique was 12%, 20%, 31%, and 42% (p < 0.001). Multivariate analysis demonstrated that the I-3D technique was an independent predictor of improved target coverage, reduced urethral dose, and more rapid resolution of urinary-related symptoms. The improved dosimetric conformity with the I-3D technique did not compromise the biochemical outcome, as the 4-year actuarial prostate-specific antigen relapse-free survival rate for this group was 97%.
  
  
  CONCLUSIONS
  The integration of an intraoperative optimization program with 3D dose evaluation throughout the target volume for prostate brachytherapy has consistently achieved excellent target coverage with the PD, and the dose levels to normal tissues were effectively restricted to tolerance ranges. These changes have led to a more favorable acute toxicity profile for patients treated with this technique without compromising biochemical control.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. zelefskm@mskcc.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
authors.forename: Christine
authors.initials: C
authors.lastname: Marion
authors.forename: Sang
authors.initials: S
authors.lastname: Sim
authors.forename: Gilad
authors.initials: G
authors.lastname: Cohen
authors.forename: Leah
authors.initials: L
authors.lastname: Ben-Porat
authors.forename: David
authors.initials: D
authors.lastname: Silvern
authors.forename: Marco
authors.initials: M
authors.lastname: Zaider
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D021621:Imaging, Three-Dimensional; D007432:Intraoperative Period; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010537:Peritoneum; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D012002:Rectal Diseases / Q000517:prevention & control; D018084:Ultrasonography, Interventional; D014522:Urethral Diseases / Q000517:prevention & control
chemical_list: D007457:Iodine Radioisotopes; D017430:Prostate-Specific Antigen