Effect of the timing of hydrogel spacer placement on prostate and rectal dosimetry of low-dose-rate brachytherapy implants.

PURPOSE: To verify the dose sparing effect of hydrogel spacer (SpaceOAR™) on rectal dosimetry for prostate brachytherapy, and to determine whether prostate and rectal dosimetry was affected by the time gap between hydrogel spacer injection and brachytherapy dosimetry. MATERIAL AND METHODS: The 103Pd brachytherapy dosimetry of 174 consecutive intermediate- and high-risk patients injected with hydrogel was compared with a dosimetry of 174 contemporaneous patients without hydrogel injections. Of the SpaceOAR™ patients, 91 had hydrogel injected upon completion of brachytherapy implant, while the remaining 83 patients had hydrogel placed prior to external beam radiation therapy (EBRT), followed 2-10 weeks later by brachytherapy. Brachytherapy implants were either planned with the prostate undistorted by any hydrogel or planned with hydrogel in place. Dosimetry of the prostate and tissues at risk was determined from CT imaging on the day of brachytherapy implant. RESULTS: SpaceOAR™ significantly reduced mean and maximum rectal doses as well as rectal wall V50, but there was a statistically significant reduction of planning target volume (PTV) D90 to 121.1% of the prescribed dose in hydrogel patients compared to 123.3% in the non-hydrogel patients. Rectal dosimetry was similar between patients injected with hydrogel after brachytherapy and those with spacer injected prior to EBRT. However, patients who had hydrogel placed prior to EBRT had statistically significantly higher dosimetry indices of PTV and urethra relative to those with spacer placed at the completion of brachytherapy. CONCLUSIONS: There was a significant rectal dose sparing in the cohort with hydrogel spacer compared to a reference group without spacer injection. The rectal dose sparing effect was similar in the sub-group of patients injected with hydrogel prior to EBRT and the sub-group injected with hydrogel at the conclusion of brachytherapy.

Effect of metal hip prosthesis on the accuracy of electromagnetic localization tracking.

PURPOSE: To quantify the effect of metal hip prosthesis on the ability to track and localize electromagnetic transponders. METHODS AND MATERIALS: Three Calypso Beacon (Varian Medical Systems, Palo Alto, CA) transponders were implanted into 2 prostate phantoms. The geometric center of the transponders were identified on computed tomography and set as the isocenter. With the phantom stationary on the treatment table and the tracking array 14-cm above the isocenter, data were acquired by the Calypso system at 10 Hz to establish the uncertainty in measurements. Transponder positional data were acquired with unilateral hip prostheses of different metallic compositions and then with bilateral hips placed at variable separation from the phantom. RESULTS: Regardless of hip prosthesis composition, the average vector displacement in the presence of a unilateral prosthesis was <0.5 mm. The greatest contribution to overall vector displacement occurred in the lateral dimension. With bilateral hip prosthesis, the average vector displacement was 0.3 mm. The displacement in the lateral dimension was markedly reduced compared with a unilateral hip, suggesting that there was a countervailing effect with bilateral hip prosthesis. The greatest average vector displacement was 0.6 mm and occurred when bilateral hip prostheses were placed within 4 cm of the detector array. CONCLUSIONS: Unilateral and bilateral hip prostheses did not have any meaningful effect on the ability to accurately track electromagnetic transponders implanted in a prostate phantom. At clinically realistic distances between the hip and detection array, the average tracking error is negligible.

Intrafraction displacement of prone versus supine prostate positioning monitored by real-time electromagnetic tracking.

Implanted radiofrequency transponders were used for real-time monitoring of the intrafraction prostate displacement between patients in the prone position and the same patients in the supine position. Thirteen patients had three transponders implanted transperineally and were treated prone with a custom-fitted thermoplastic immobilization device. After collecting data from the last fraction, patients were realigned in the supine position and the displacements of the transponders were monitored for 5-7 minutes. Fourier transforms were applied to the data from each patient to determine periodicity and its amplitude. To remove auto correlation from the stream of displacement data, the distribution of short-term and long-term velocity components were calculated from Poincaré plots of paired sequential vector displacements. The mean absolute displacement was significantly greater prone than supine in the superior-inferior (SI) plane (1.2 ± 0.6 mm vs. 0.6 ± 0.4 mm, p= 0.015), but not for the lateral or anterior-posterior (AP) planes. Displacements were least in the lateral direction. Fourier analyses showed the amplitude of respiratory oscillations was much greater for the SI and AP planes in the prone versus the supine position. Analysis of Poincaré plots confirmed greater short-term variance in the prone position, but no difference in the long-term variance. The centroid of the implanted transponders was offset from the treatment isocenter by > 5 mm for 1.9% of the time versus 0.8% of the time for supine. These results confirmed significantly greater net intrafraction prostate displacement of patients in the prone position than in the supine position, but most of the difference was due to respiration-induced motion that was most pronounced in the SI and AP directions. Because the respiratory motion remained within the action threshold and also within our 5 mm treatment planning margins, there is no compelling reason to choose one treatment position over the other.

Effect of body mass index on intrafraction prostate displacement monitored by real-time electromagnetic tracking.

PURPOSE: To evaluate, using real-time monitoring of implanted radiofrequency transponders, the intrafraction prostate displacement of patients as a function of body mass index (BMI). METHODS AND MATERIALS: The motions of Beacon radiofrequency transponders (Calypso Medical Technologies, Seattle, WA) implanted in the prostate glands of 66 men were monitored throughout the course of intensity modulated radiation therapy. Data were acquired at 10 Hz from setup to the end of treatment, but only the 1.7 million data points with a "beam on" tag were used in the analysis. There were 21 obese patients, with BMI ≥ 30 and 45 nonobese patients in the study. RESULTS: Mean displacements were least in the left-right lateral direction (0.56 ± 0.24 mm) and approximately twice that magnitude in the superior-inferior and anterior-posterior directions. The net vector displacement was larger still, 1.95 ± 0.47 mm. Stratified by BMI cohort, the mean displacements per patient in the 3 Cartesian axes as well as the net vector for patients with BMI ≥ 30 were slightly less (<0.2 mm) but not significantly different than the corresponding values for patients with lower BMIs. As a surrogate for the magnitude of oscillatory noise, the standard deviation for displacements in all measured planes showed no significant differences in the prostate positional variability between the lower and higher BMI groups. Histograms of prostate displacements showed a lower frequency of large displacements in obese patients, and there were no significant differences in short-term and long-term velocity distributions. CONCLUSIONS: After patients were positioned accurately using implanted radiofrequency transponders, the intrafractional displacements in the lateral, superior-inferior, and anterior-posterior directions as well as the net vector displacements were smaller, but not significantly so, for obese men than for those with lower BMI.

Electromagnetic transponders indicate prostate size increase followed by decrease during the course of external beam radiation therapy.

PURPOSE: Real-time image guidance enables more accurate radiation therapy by tracking target movement. This study used transponder positions to monitor changes in prostate volume that may be a source of dosimetric and target inaccuracy. METHODS AND MATERIALS: Twenty-four men with biopsy-proven T1c-T3a prostate cancer each had three electromagnetic transponders implanted transperineally. Their coordinates were recorded by the Calypso system, and the perimeter of the triangle formed by the transponders was used to calculate prostate volumes at sequential time points throughout the course of radiation therapy to a dose of 81 Gy in 1.8-Gy fractions. RESULTS: There was a significant decrease in mean prostate volume of 10.9% from the first to the final day of radiation therapy. The volume loss did not occur monotonically but increased in most patients (75%) during the first several weeks to a median maximum on Day 7. The volume increased by a mean of 6.1% before decreasing by a mean maximum difference of 18.4% to nadir (p < 0.001 for both increase and decrease). Glandular shrinkage was asymmetric, with the apex to right base dimension varying more than twice that of the lateral dimension. For all dimensions, the mean change was <0.5 cm. CONCLUSION: Real-time transponder positions indicated a volume increase during the initial days of radiation therapy and then significant and asymmetric shrinkage by the final day. Understanding and tracking volume fluctuations of the prostate during radiation therapy can help real-time imaging technology perform to its fullest potential.

Electromagnetic tracking of intrafraction prostate displacement in patients externally immobilized in the prone position.

PURPOSE: To evaluate intrafraction prostate displacement among patients immobilized in the prone position using real-time monitoring of implanted radiofrequency transponders. METHODS AND MATERIALS: The Calypso localization system was used to track prostate motion in patients receiving external beam radiation therapy (XRT) for prostate cancer. All patients were treated in the prone position and immobilized with a thermoplastic immobilization device. Real-time measurement of prostate displacement was recorded for each treatment fraction. These measurements were used to determine the duration and magnitude of displacement along the three directional axes. RESULTS: The calculated centroid of the implanted transponders was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 38.0%, 13.9%, and 4.5% of the time. In the lateral dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 2.7%, 0.4%, and 0.06% of the time. In the superior-inferior dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 16.1%, 4.7%, and 1.5% of the time, respectively. In the anterior-posterior dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 13.4%, 3.0%, and 0.5% of the time. CONCLUSIONS: Intrafraction prostate displacement in the prone position is comparable to that in the supine position. For patients with large girth, in whom the supine position may preclude accurate detection of implanted radiofrequency transponders, treatment in the prone position is a suitable alternative.

cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer.

BACKGROUND: To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer. METHODS: 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. RESULTS: The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment. CONCLUSION: Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes.

Erectile function durability following permanent prostate brachytherapy.

PURPOSE: To evaluate long-term changes in erectile function following prostate brachytherapy. METHODS AND MATERIALS: This study included 226 patients with prostate cancer and preimplant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) who underwent brachytherapy in two prospective randomized trials between February 2001 and January 2003. Median follow-up was 6.4 years. Pre- and postbrachytherapy potency was defined as IIEF-6 > or = 13 without pharmacologic or mechanical support. The relationship among clinical, treatment, and dosimetric parameters and erectile function was examined. RESULTS: The 7-year actuarial rate of potency preservation was 55.6% with median postimplant IIEF of 22 in potent patients. Potent patients were statistically younger (p = 0.014), had a higher preimplant IIEF (p < 0.001), were less likely to be diabetic (p = 0.002), and were more likely to report nocturnal erections (p = 0.008). Potency preservation in men with baseline IIEF scores of 29-30, 24-28, 18-23, and 13-17 were 75.5% vs. 73.6%, 51.7% vs. 44.8%, 48.0% vs. 40.0%, and 23.5% vs. 23.5% in 2004 vs. 2008. In multivariate Cox regression analysis, preimplant IIEF, hypertension, diabetes, prostate size, and brachytherapy dose to proximal penis strongly predicted for potency preservation. Impact of proximal penile dose was most pronounced for men with IIEF of 18-23 and aged 60-69. A significant minority of men who developed postimplant impotence ultimately regained erectile function. CONCLUSION: Potency preservation and median IIEF scores following brachytherapy are durable. Thoughtful dose sparing of proximal penile structures and early penile rehabilitation may further improve these results.

Erectile function after prostate brachytherapy.

PURPOSE: To evaluate erectile function after permanent prostate brachytherapy using a validated patient-administered questionnaire and to determine the effect of multiple clinical, treatment, and dosimetric parameters on penile erectile function. METHODS AND MATERIALS: A total of 226 patients with preimplant erectile function determined by the International Index of Erectile Function (IIEF) questionnaire underwent permanent prostate brachytherapy in two prospective randomized trials between February 2001 and January 2003 for clinical Stage T1c-T2c (2002 American Joint Committee on Cancer) prostate cancer. Of the 226 patients, 132 were potent before treatment and, of those, 128 (97%) completed and returned the IIEF questionnaire after brachytherapy. The median follow-up was 29.1 months. Potency was defined as an IIEF score of > or =13. The clinical, treatment, and dosimetric parameters evaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigen level; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presence of hypertension or diabetes mellitus; tobacco consumption; the volume of the prostate gland receiving 100%, 150%, and 200% of the prescribed dose (V(100/150/200)); the dose delivered to 90% of the prostate gland (D(90)); androgen deprivation therapy; supplemental external beam radiotherapy (EBRT); isotope; prostate volume; planning volume; and radiation dose to the proximal penis. RESULTS: The 3-year actuarial rate of potency preservation was 50.5%. For patients who maintained adequate posttreatment erectile function, the preimplant IIEF score was 29, and in patients with brachytherapy-related ED, the preimplant IIEF score was 25. The median time to the onset of ED was 5.4 months. After brachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariate analysis, the preimplant IIEF score, patient age, presence of nocturnal erections, and dose to the proximal penis predicted for postimplant erectile function. However, in multivariate analysis, only the preimplant IIEF score and the D(50) to the proximal crura were statistically significant predictors of brachytherapy-related erectile function. CONCLUSIONS: Using a patient-administered validated quality-of-life instrument, brachytherapy-induced ED occurred in 50% of patients at 3 years. On multivariate analysis, preimplant erectile function and the D(50) to the proximal crura were the best predictors of brachytherapy-related erectile function. Because the proximal penis is the most significant treatment-related predictor of brachytherapy-related ED, techniques to minimize the radiation dose to the proximal penis may result in improved rates of potency preservation.

Permanent prostate brachytherapy-induced morbidity in patients with grade II and III obesity.

OBJECTIVES: To determine the influence of obesity on the development of urinary, bowel, and sexual dysfunction after brachytherapy by means of patient-administered questionnaires. The effect of obesity on dosimetric quality and biochemical outcome was also evaluated. METHODS: Thirty-two patients with grade II and III obesity underwent brachytherapy from June 1997 through April 2001. Grade II and III obesity was defined as a body mass index of 35.0 to 39.9 and 40.0 kg/m2 or greater, respectively. Serial International Prostate Symptom Score (IPSS) evaluations were obtained at predetermined intervals. Bowel and sexual function were assessed by a rectal function assessment score (R-FAS) and the specific erectile questions of the International Index of Erectile Function (IIEF). The median follow-up was 26.4 months. An alpha-blocker was initiated before implantation and continued at least until the IPSS normalized. Catheter dependency, alpha-blocker dependency, and the incidence of urethral strictures were also evaluated. The efficacy of sildenafil in brachytherapy-induced erectile dysfunction was also evaluated. Dosimetric parameters evaluated included the percentage of the prostate receiving 100%, 150%, and 200% of the prescribed dose (V100, V150, and V200), the minimal dose received by 90% of the prostate (D90), urethral doses, and rectal doses. Biochemical outcome was determined by the ASTRO consensus conference definition. RESULTS: Of the 32 patients, 31 (97%) had the urinary catheter permanently removed on day 0, and no patient required a urinary catheter for longer than 1 day. One patient developed a urethral stricture. No patient required a transurethral resection or developed urinary incontinence. On average, the IPSS peaked 2 weeks after implantation and returned to baseline at a median of 8 weeks (mean 16). The post-treatment R-FAS was 3.6. No patient developed a rectal ulcer or fistula. Of the 22 patients who were potent before implantation, 7 (31.8%) maintained potency. With pharmacologic support, 59.1% maintained erections sufficient for vaginal penetration. Day 0 dosimetry demonstrated a median V100 and D90 of 96.5% and 113.5%. At last follow-up, all patients remained free of biochemical failure, with a median prostate-specific antigen level of 0.1 ng/mL. CONCLUSIONS: No difference in quality-of-life parameters was discerned in patients with grade II and III obesity. In addition, the dosimetric quality of the implants was outstanding, and the short-term biochemical outcome was encouraging.