Seed loss in prostate brachytherapy : Operator dependency and impact on dosimetry.

INTRODUCTION: The aim of our study was to review seed loss and its impact on dosimetry as well as the influence of the treating physician on seed loss and dosimetry in patients treated with prostate brachytherapy using permanent loose (125)I implant. PATIENTS AND METHODS: We analyzed 1087 consecutive patients treated by two physicians between July 2005 and April 2015 at a single institution. Pelvic fluoroscopic imaging was done 30 days post implant and a chest X-ray when seed loss was observed. RESULTS: Seed loss occurred in 19.4 % of patients: in 20.0 % of implants done by the most experienced physician and in 17.2 % by the less experienced physician (p = 0.4) and migration to the thorax occurred in 5.9 % (6.9 vs. 2.2 %, p = 0.004). The mean seed loss rate was 0.57 % [standard deviation (SD) 1.39] and the mean rate of seeds in the thorax was 0.14 % (SD 0.65). The most experienced physician had a higher mean number of seeds lost: 0.36 versus 0.25 (p = 0.055), and a higher mean number of seed migration to the thorax: 0.1 versus 0.02 (p < 0.001). When at least one seed was lost, a decrease of 4.2 Gy (p < 0.001) in the D90 and a decrease of 3.5 % (p = 0.002) in the V150 was observed. CONCLUSION: We found a significant decrease in V150 and D90 with the occurrence of seed loss. Furthermore, we found a difference in seed migration among the physicians demonstrating that seed loss is operator dependant.

Poor predictive value of intraoperative real-time dosimetry for prostate seed brachytherapy.

PURPOSE: To identify dosimetric parameters predictive of a good prostate seed I(125) quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning. METHODS AND MATERIALS: We analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I(125) brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of > or =90% and a D90 of > or =140 Gy on the basis of CT-D28 values. RESULTS: On CT-D28, 72.4% of patients had a V100 of > or =90% and 74.8% had a D90 of > or =140 Gy. AUROC for a V100 of > or =90% was 0.665 (p = 0.004) on PRE-TRUS and 0.619 (p = 0.039) on POST-TRUS. AUROC for D90 of > or =140 Gy was 0.602 (p = 0.086) on PRE-TRUS and 0.614 (p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%. CONCLUSIONS: Because of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography-based dosimetry.

Fusion of Intraoperative Transrectal Ultrasound Images with Post-implant Computed Tomography and Magnetic Resonance Imaging.

Purpose To compare the impact of the fusion of intraoperative transrectal ultrasound (TRUS) images with day 30 computed tomography (CT) and magnetic resonance imaging (MRI) on prostate volume and dosimetry. Methods and materials Seventy-five consecutive patients with CT and MRI obtained on day 30 with a Fast Spin Echo T2-weighted magnetic resonance (MR) sequence were analyzed. A rigid manual registration was performed between the intraoperative TRUS and day-30 CT based on the prostate volume. A second manual rigid registration was performed between the intraoperative TRUS and the day-30 MRI. The prostate contours were manually modified on CT and MRI. The difference in prostate volume and dosimetry between CT and MRI were compared. Results Prostate volume was on average 8% (standard deviation (SD) ± 16%) larger on intraoperative TRUS than on CT and 6% (18%) larger than on MRI. In 48% of the cases, the difference in volume on CT was > 10% compared to MRI. The difference in prostate volume between CT and MRI was inversely correlated to the difference in D90 (minimum dose that covers 90% of the prostate volume) between CT and MRI (r = -0.58, P < .001). A D90 < 90% was found in 5% (n = 4) on MRI and in 10% (n = 7) on CT (Fisher exact test one-sided P = .59), but in no patient was the D90 < 90% on both MRI and CT. Conclusions When fusing TRUS images with CT and MRI, the differences in prostate volume between those modalities remain clinically important in nearly half of the patients, and this has a direct influence on how implant quality is evaluated.

Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results.

PURPOSE: To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. MATERIAL AND METHODS: From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. RESULTS: All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn't receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%. CONCLUSIONS: Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.

Refining prostate seed brachytherapy: Comparing high-, intermediate-, and low-activity seeds for I-125 permanent seed prostate brachytherapy.

PURPOSE: To analyze the difference in prostate coverage and dose to the rectum in men with prostate carcinoma treated with permanent seed brachytherapy with different seed activities. METHODS: Forty-nine patients treated with iodine-125 permanent seed prostate brachytherapy with low-activity seeds of 0.30-0.37 mCi were identified. For each of these patients, 2 patients with similar prostate volume (±2 cc) were paired: one treated with intermediate seed activity (0.44-0.46 mCi) and one with high seed activity (0.60-0.66 mCi). The doses to prostate and rectum were compared using CT on Day 30. RESULTS: A total of 147 patients divided into the three seed activity groups were analyzed. Mean prostate volume was 35.7 cc (standard deviation [SD], 11.70). Compared with low-activity seeds, implants with high-activity seeds consisted of an average of 22 seeds and 4.7 needles less. The dose to the prostate (prostate volume receiving 100% of the prescribed dose [V100], prostate volume receiving 150% of the prescribed dose, and minimal dose covering 90% of the prostate volume expressed in Gy) was not higher on Day 30 (p = 0.58-0.97). The mean volume (in cubic centimeters) of rectal wall receiving 100% of the prescribed dose (V100) increased with activity: low activity, 0.34 cc (SD, 0.49), intermediate activity, 0.47 cc (SD, 0.48), and high activity, 0.72 cc (SD, 0.79) (p = 0.009). There was a trend (p = 0.073) toward a higher frequency of clinically unfavorable rectal dosimetry (V100 > 1.3 cc) in patients with high-activity seeds (16.7%) compared with low-activity (6.3%) or intermediate-activity (4.2%) seeds. CONCLUSION: High-activity seeds do not result in a higher dose to the prostate but in a higher dose to the rectum.

Seed migration in prostate brachytherapy depends on experience and technique.

PURPOSE: To determine seed loss and pulmonary migration rate over time in permanent seed prostate brachytherapy. METHODS AND MATERIALS: We analyzed the first 495 patients treated in our department. All patients were treated with loose (125)I seeds with automated seed delivery system and real-time intraoperative planning. Pelvic fluoroscopic imaging was done 30 days after the implant. Patients were divided into five groups of 100 patients according to the order they were treated, and groups were compared using χ(2) test and one-way analysis of variance. RESULTS: A total of 22.8% of patients lost at least one seed. The highest percentage of patients losing any number of seeds was in the first 100. Thirty-eight percent lost at least one seed. This number decreased gradually and was only 9% in Patients 400-499. The mean total seed loss rate (number of seeds lost/number seeds implanted) changed significantly over time (p<0.001). There was a continuous significant (p<0.001) decline after the first 100 patients (1.25% for the first 100 patients) followed by a rise in Patients 300-399, followed by another decline (0.21% for the last 100 patients). The seed loss rate to the thorax changed significantly over time (p=0.009). It rose after an initial rate of 0.25-0.42% in Patients 200-299 and 300-399 and declined later to a rate of 0.21% in the last 100 patients. CONCLUSIONS: We found a learning curve for seed migration. Avoiding implanting seeds outside of the capsule and modern transrectal ultrasound imaging can help decrease migration.

Analysis of seed loss and pulmonary seed migration in patients treated with virtual needle guidance and robotic seed delivery.

PURPOSE AND BACKGROUND: To determine whether automated seed delivery system and real-time intraoperative (IO) virtual needle guidance reduce seed loss and pulmonary seed migration. PATIENTS AND METHODS: We analyzed 279 patients with low and intermediate risk prostate cancer treated in our institution with radioactive iodine (I-125) permanent seed implants. Loose seeds were exclusively used. To account for lost seeds, pelvic fluoroscopic imaging from 3 different angles was done 30 days after the implant. Posteroanterior and lateral chest x-rays were done when seed loss was confirmed. Patients were compared using the χ(2) test and Fisher exact test. RESULTS: At least 1 seed was lost in 31.5% of patients with a migration rate of 1.02%; 9.3% of patients had at least 1 seed in the lung with a migration rate of 0.22%. The population was divided into 3 groups according to the order in which they were treated. Seed loss (P=0.02) and pulmonary seed embolization (P=0.008) were significantly lower in the second hundred than in the first hundred patients. No difference was noted between groups 1 and 3 (patient, 201-279). Peri- or extracapsular seed placement was not correlated to seed loss (P=0.780 and P=0.092, respectively). No serious complications from seed migration were reported. Seed loss did not influence dosimetry parameters (V100, V150, and D90). CONCLUSION: Our pulmonary seed migration and total seed loss rates are comparable to the ones reported in the literature. Virtual needle guidance and automated seed delivery system are in our hand as accurate as the manual technique.

Urethra-sparing, intraoperative, real-time planned, permanent-seed prostate brachytherapy: toxicity analysis.

PURPOSE: To report the toxicity outcome in patients with localized prostate cancer undergoing (125)I permanent-seed brachytherapy (BT) according to a urethra-sparing, intraoperative (IO), real-time planned conformal technique. METHODS AND MATERIALS: Data were analyzed on 250 patients treated consecutively for low- or intermediate-risk prostate cancer between 2005 and 2009. The planned goal was urethral V(150) = 0. Acute and late genitourinary (GU), gastrointestinal (GI), and erectile toxicities were scored with the International Prostate Symptom Score (IPSS) questionnaire and Common Terminology Criteria for Adverse Events (version 3.0). Median follow-up time for patients with at least 2 years of follow-up (n = 130) was 34.4 months (range, 24-56.9 months). RESULTS: Mean IO urethra V(150) was 0.018% ± 0.08%. Mean prostate D(90) and V(100) on day-30 computed tomography scan were 158.0 ± 27.0 Gy and 92.1% ± 7.2%, respectively. Mean IPSS peak was 9.5 ± 6.3 1 month after BT (mean difference from baseline IPSS, 5.3). No acute GI toxicity was observed in 86.8% of patients. The 3-year probability of Grade ≥2 late GU toxicity-free survival was 77.4% ± 4.0%, with Grade 3 late GU toxicity encountered in only 3 patients. Three-year Grade 1 late GI toxicity-free survival was 86.1% ± 3.2%. No patient presented Grade ≥2 late GI toxicity. Of patients with normal sexual status at baseline, 20.7% manifested Grade ≥2 erectile dysfunction after BT. On multivariate analysis, elevated baseline IPSS (p = 0.016) and high-activity sources (median 0.61 mCi) (p = 0.033) predicted increased Grade ≥2 late GU toxicity. CONCLUSIONS: Urethra-sparing IO BT results in low acute and late GU toxicity compared with the literature. High seed activity and elevated IPSS at baseline increased long-term GU toxicity.

Comparison between high and low source activity seeds for I-125 permanent seed prostate brachytherapy.

PURPOSE: To compare low (mean 0.44, SD ± 0.0163 mCi) with high source activity (0.61 ± 0.0178 mCi) in I(125) permanent seed brachytherapy regarding seed loss, dosimetric outcome, and toxicity. METHODS AND MATERIALS: The study included 199 patients with prostate cancer treated by permanent seed brachytherapy alone: the first 105 with seeds of lower activity (first cohort), the following 94 with higher seed activity (second cohort). The V100, V150, V200, and D90 were analyzed on the CT scan 30 days after implantation (CTD30). The V100, V150, and D2 of the rectum were also calculated on CTD30. Seed loss was determined 30 days after implantation. Urinary toxicity was measured with the International Prostate Symptom Score (IPSS) questionnaire. RESULTS: Lower seed activity was associated with lower V150 and V200 (p = 0.01 and p ≤ 0.001, respectively) on CTD30. More patients had a V100 <90% and D90 <140 Gy in the lower activity cohort (p = 0.098 for D90 and p = 0.029 for V100) on CTD30. There was no difference between cohorts in dose to the rectum (p = 0.325-0.516) or difference in patients' IPSS score from baseline (p = 0.0.117-0.618), although there was a trend toward more urinary toxicity at 4 and 8 months for high activity seeds. Seed loss as a percentage of implanted seeds was not different (p = 0.324). CONCLUSIONS: Higher seed activity (I(125) ≥ 0.6 mCi) results in at least equal V100 and D90 on CTD30. However, dose inhomogeneity and a trend toward more urinary toxicity at 4 and 8 months after treatment may lead to a higher long-term urinary complications.