Jette Borg

10-year experience with I-125 prostate brachytherapy at the Princess Margaret Hospital: results for 1,100 patients.

PURPOSE To report outcomes for 1,111 men treated with iodine-125 brachytherapy (BT) at a single institution. METHODS AND MATERIALS A total of 1,111 men (median age, 63) were treated with iodine-125 prostate BT for low- or intermediate-risk prostate cancer between March 1999 and November 2008. Median prostate-specific antigen (PSA) level was 5.4 ng/ml (range, 0.9-26.1). T stage was T1c in 66% and T2 in 34% of patients. Gleason score was 6 in 90.1% and 7 or 8 in 9.9% of patients. Neoadjuvant hormonal therapy (2-6 months course) was used in 10.1% of patients and combined external radiotherapy (45 Gy) with BT (110 Gy) in 4.1% (n = 46) of patients. Univariate and multivariate Cox proportional hazards were used to determine predictors of failure. RESULTS Median follow-up was 42 months (range, 6-114), but for biochemical freedom from relapse, a minimum PSA test follow-up of 30 months was required (median 54; n = 776). There were 27 failures, yielding an actuarial 7-year disease-free survival rate of 95.2% (96 at risk beyond 84 months). All failures underwent repeat 12-core transrectal ultrasound -guided biopsies, confirming 8 local failures. On multivariate analysis, Gleason score was the only independent predictor of failure (p = 0.001; hazard ratio, 4.8 (1.9-12.4). Median International Prostate Symptom score from 12 to 108 months ranged between 3 and 9. Of the men reporting baseline potency, 82.8% retained satisfactory erectile function beyond 5 years. CONCLUSION Iodine-125 prostate BT is a highly effective treatment option for favorable- and intermediate-risk prostate cancer and is associated with maintenance of good urinary and erectile functions.

Sequential Comparison of Seed Loss and Prostate Dosimetry of Stranded Seeds With Loose Seeds in 125I Permanent Implant for Low-Risk Prostate Cancer

PURPOSE To compare stranded seeds (SSs) with loose seeds (LSs) in terms of prostate edema, dosimetry, and seed loss after (125)I brachytherapy. METHODS AND MATERIALS Two prospective cohorts of 20 men participated in an institutional review board-approved protocols to study postimplant prostate edema and its effect on dosimetry. The LS cohort underwent brachytherapy between September 2002 and July 2003 and the SS cohort between April 2006 and January 2007. Both cohorts were evaluated sequentially using computed tomography-magnetic resonance imaging fusion-based dosimetry on Days 0, 7, and 30. No hormonal therapy or supplemental beam radiotherapy was used. RESULTS Prostate edema was less in the SS cohort at all points (p = NS). On Day 0, all the prostate dosimetric factors were greater in the LS group than in the SS group (p = 0.003). However, by Days 7 and 30, the dosimetry was similar between the two cohorts. No seeds migrated to the lung in the SS cohort compared with a total of five seeds in 4 patients in the LS cohort. However, the overall seed loss was greater in the SS cohort (24 seeds in 6 patients; 1.1% of total vs. 0.6% for LSs), with most seeds lost through urine (22 seeds in 5 patients). CONCLUSION Despite elimination of venous seed migration, greater seed loss was observed with SSs compared with LSs, with the primary site of loss being the urinary tract. Modification of the technique might be necessary to minimize this. Prostate dosimetry on Days 7 and 30 was similar between the SS and LS cohorts.

Magnetic Resonance Imaging–Defined Treatment Margins in Iodine-125 Prostate Brachytherapy

PURPOSE Low-dose-rate prostate brachytherapy achieves a very high and effective intraprostatic dose. Implant quality parameters concentrate on the dose received by the prostate (D90, V100) but not that received by the periprostatic tissue. We calculated implant quality parameters, D90 and V100, for the magnetic resonance imaging (MRI)-defined prostate plus 2, 3, and 5 mm. METHODS AND MATERIALS A total of 131 men with early-stage prostate cancer treated with iodine-125 brachytherapy represent all those treated with brachytherapy monotherapy in our institution in 2005. Postplan assessment was performed at 1 month using magnetic resonance (MR)-computed tomography (CT) fusion. The prostate V100 and D90 were calculated with 2-, 3-, and 5-mm margins. Results were compared with those in 8 patients with biopsy-proven local failure occurring in an experience of more than 1,100 implants. RESULTS Mean prostate V100 (SD) and D90 (SD) were 95.6% (4.1) and 117.2% (12.7). For prostate plus a 2-mm margin the D90 was 107.9% (14.3) and for a 3-mm margin 96.0 % (14.0). For prostate plus a 5-mm margin, the D90 was only 78.4% (11.0). The 8 patients experiencing local failure, despite adequate implants, had a lower mean V100 of 91.2% (SD, 2.8; p = 0.0008) and D90 of 103.7% (SD, 8.3; p = 0.002) and significantly inferior margin coverage. CONCLUSIONS Satisfactory coverage of a 2-mm and 3-mm periprostatic margin is obtained with the described planning approach. Coverage falls off significantly by 5 mm. The 8 patients who experienced local failure had significantly lower doses than the margin cohort. Although the V100 and D90 would be considered acceptable, the fall-off in margin coverage was observed by 3 mm.

The effect of obesity on rectal dosimetry after permanent prostate brachytherapy

OBJECTIVES Men with higher body mass index (BMI) tend to have more fatty tissue in prostate-rectum interface, which may reduce the rectal wall dose by the inverse square law. We hypothesized that men with higher BMI will have a lower dose to the rectal wall and less rectal toxicity after permanent prostate implant. METHODS Prospectively collected data on rectal dosimetry/toxicity and BMI of 407 patients who underwent iodine-125 ((125)I) prostate implant were analyzed. Postimplant dosimetry used CT-MRI fusion on Day 30. Rectal wall was contoured on all slices where seeds were seen. The volume of rectal wall receiving the prescribed dose (RV(100) in cm(3)) and the dose to 1cc of rectal wall (RD(1cc)) were reported. Other factors evaluated for association with rectal dosimetry and toxicity included age, diabetes, hypertension, smoking, use of neoadjuvant hormones, T stage, baseline prostate volume, 1 month prostate edema, seed type and activity, and prostate dosimetry factors (the isodose enclosing 90% of the prostate volume [D(90)], the percentage of the prostate volume enclosed by the prescription [V(100)], and the percentage of the prostate volume enclosed by the 150% isodose [V(150)]). Rectal toxicity was reported as per Radiation Therapy Oncology Group criteria. RESULTS BMIs ranged from 15.9 to 46.8 (mean+/-standard deviation [SD]: 27.8+/-4.2). The mean+/-SD values for RV(100) and RD(1cc) were 0.79+/-0.49cm(3) and 128.2+/-27.8Gy, respectively. There was a significant negative association of BMI with RV(100) (p=0.007) and RD(1cc) (p=0.01) on univariate analysis. The mean RV(100) and RD(1cc) for men with higher BMI (>27.8) were lower compared with their slimmer counterparts (0.70 vs. 0.86cm(3) and 123.4 vs. 132.4Gy, respectively). On multivariate analysis for RV(100) and RD(1cc), BMI remained significant (p-values 0.004 and 0.01, respectively) along with prostate volume and V(150), suggesting that anatomic factors are important in rectal dosimetry in prostate brachytherapy. Overall the incidence of Radiation Therapy Oncology Group acute rectal toxicity was 12% (Grade 2, 1.3%) and chronic 6% (Grade 2, 0.5%). No Grade 3 toxicity occurred. None of the factors evaluated were predictive for rectal toxicity. CONCLUSION Men with a lower BMI received a higher rectal wall dose compared with those with higher BMI. This did not, however, translate into greater rectal toxicity.

Loose seeds vs. stranded seeds: A comparison of critical organ dosimetry and acute toxicity in 125I permanent implant for low-risk prostate cancer

PURPOSE To compare the critical organ dosimetry and toxicity of loose seeds (LS) with stranded seeds (SS) in (125)I permanent implant for low-risk prostate cancer. METHODS AND MATERIALS Two cohorts of 20 patients each were treated in Institutional Review Board-approved protocols designed to assess prostate edema and seed stability using MR-CT fusion on Days 0, 7, and 30 after permanent implant. (125)I LS were used for one cohort and (125)I SS for the other. Rectal wall dosimetry was compared for the two cohorts using RV100 and RD1cc and urethral dosimetry using UD5, UD30, and UV150. Statistical comparisons were performed using unpaired Students t test. RESULTS At each time point (Days 0, 7, and 30), both the mean RD1 cc (SS: 123.1, 139.7, and 156.1 Gy vs. LS: 90.2, 104, and 129.4 Gy, respectively) and the mean RV100 (SS: 0.63, 1.0, and 1.4 cc vs. LS: 0.2, 0.4, and 0.73 cc, respectively) were significantly higher for strands (all p-values<0.01). Only 1 patient developed radiotherapy oncology group (RTOG) Grade 1 acute rectal toxicity in the loose seed cohort, whereas 3 patients had Grade 1 and 1 patient had Grade 2 toxicity with strands. The mean percentage increase of UD5 (7.7% LS vs. 24.6% SS; p=0.004) and UD30 (5% LS vs. 15.9% SS; p=0.02) from preplan to Day 30 was higher for strands. The increase in UV150 from baseline to Day 30 was significantly higher for strands (0.2 vs. 0.06 cc; p=0.01). Urinary toxicity was similar in both cohorts. CONCLUSIONS SS resulted in higher dose to urethra and rectal wall compared with LS on postimplant dosimetry. A trend toward higher acute rectal toxicity rate was observed for SS.

A Phase III Randomized Trial of the Timing of Meloxicam With Iodine-125 Prostate Brachytherapy

PURPOSE Nonsteroidal anti-inflammatory medication is used to reduce prostate edema and urinary symptoms following prostate brachytherapy. We hypothesized that a cyclooxygenase-2 (COX-2) inhibitor regimen started 1 week prior to seed implant might diminish the inflammatory response, thus reducing edema, retention rates, and symptom severity. METHODS AND MATERIALS From March 2004 to February 2008, 316 men consented to an institutional review board-approved randomized study of a 4-week course of meloxicam, 7.5 mg orally twice per day, starting either on the day of implant or 1 week prior to implant. Brachytherapy was performed using iodine-125 seeds and was preplanned and performed under transrectal ultrasound (TRUS) and fluoroscopic guidance. Prostate volume obtained by MR imaging at 1 month was compared to baseline prostate volume obtained by TRUS planimetry and expressed as an edema factor. The trial endpoints were prostate edema at 1 month, International Prostate Symptom Score (IPSS) questionnaire results at 1 and 3 months, and any need for catheterization. RESULTS Results for 300 men were analyzed. Median age was 61 (range, 45-79 years), and median TRUS prostate volume was 35.7 cc (range, 18.1-69.5 cc). Median IPSS at baseline was 5 (range, 0-24) and was 15 at 1 month, 16 at 3 months, and 10 at 6 months. Catheterization was required for 7% of patients (6.2% day 0 arm vs. 7.9% day -7 arm; p = 0.65). The median edema factor at 1 month was 1.02 (range, 0.73-1.7). 1.01 day 0 arm vs. 1.05 day -7 arm. Baseline prostate volume remained the primary predictor of postimplant urinary retention. CONCLUSIONS Starting meloxicam 1 week prior to brachytherapy compared to starting immediately after the procedure did not reduce 1-month edema, improve IPSSs at 1 or 3 months, or reduce the need for catheterization.

Evaluation of the dosimetric impact of loss and displacement of seeds in prostate low-dose-rate brachytherapy.

Purpose To analyze the seed loss and displacement and their dosimetric impact in prostate low-dose-rate (LDR) brachytherapy while utilizing the combination of loose and stranded seeds. Material and methods Two hundred and seventeen prostate cancer patients have been treated with LDR brachytherapy. Loose seeds were implanted in the prostate center and stranded seeds in the periphery of the gland. Patients were imaged with transrectal ultrasound before implant and with computerized tomography/magnetic resonance imaging (CT/MR) one month after implant. The seed loss and displacement had been analyzed. Their impact on prostate dosimetry had been examined. The seed distribution beyond the prostate inferior boundary had been studied. Results The mean number of seeds per patient that were lost to lung, pelvis/abdomen, urine, or unknown destinations was 0.21, 0.13, 0.03, and 0.29, respectively. Overall, 40.1% of patients had seed loss. Seed migration to lung and pelvis/abdomen occurred in 15.5% and 10.5% of the patients, respectively. Documented seed loss to urine was found in 3% of the patients while 20% of patients had seed loss to unknown destinations. Prostate length difference between pre-plan and post-implant images was within 6 mm in more than 98% of cases. The difference in number of seeds inferior to prostate between pre-plan and post-implant dosimetry was within 7 seeds for 93% of patients. At time of implant, 98% of seeds, inferior to prostate, were within 5 mm and 100% within 15 mm, and in one month post-implant 83% within 9 mm and 96.3% within 15 mm. Prostate post-implant V100, D90, and rectal wall RV100 for patients without seed loss were 94.6%, 113.9%, and 0.98 cm3, respectively, as compared to 95.0%, 114.8%, and 0.95 cm3 for the group with seed loss. Conclusions Seed loss and displacement have been observed to be frequent. No correlation between seed loss and displacement and post-plan dosimetry has been reported.