Anthony T. Dorsey

Temporal resolution of urinary morbidity following prostate brachytherapy

PURPOSE To report the short-term urinary morbidity for prostate brachytherapy patients without a preimplant history of a transurethral resection of the prostate gland and who received prophylactic and prolonged alpha-blockers. alpha-blockers may decrease radiation-induced urethritis and increase urinary flow. Multiple clinical and treatment parameters were evaluated to identify factors associated with increased acute urinary morbidity. MATERIALS AND METHODS One hundred seventy consecutive patients without a prior history of a transurethral resection of the prostate gland underwent transperineal ultrasound guided prostate brachytherapy for clinical T1c-T3a carcinoma of the prostate gland. For all patients, an alpha-blocker was initiated prior to implantation and continued at least until the international prostate symptom score (IPSS) returned to baseline levels. Clinical parameters evaluated for short-term urinary morbidity included patient age, clinical T stage, preimplant IPSS (obtained within 3 weeks of implantation), and prostate ultrasound volume. Treatment parameters included the utilization of neoadjuvant hormonal manipulation, the utilization of moderate dose external beam radiation therapy before implantation, the choice of isotope, the urethral dose, the total implant activity in millicuries, and a variety of dosimetric quality indicators (D(90) and V(100)/V(150)/V(200)). Catheter dependency and the duration of alpha-blocker dependency was also evaluated. On average, 11.2 IPSS surveys were obtained for each patient. RESULTS One hundred fifty of the 170 patients (88.2%) had the urinary catheter permanently removed on day 0. Only one patient required an urinary catheter for > 5 days. Two patients (1.2%) required a subsequent transurethral resection of the prostate gland because of prolonged obstructive/irritative symptoms. To date, no patient has developed an urinary stricture or urinary incontinence. The IPS score on average peaked at 2 weeks following implantation. This score returned to within 1 point of the antecedent value at a median of 6 weeks and a mean of 13.3 weeks. At 26 and 50 weeks, 85% and 56% of the patients, respectively, continued with alpha-blockers. Of the clinical and treatment parameters evaluated for short-term urinary morbidity, only variants of the IPSS such as the maximum, maximum increase, and preimplant IPSS values correlated with time to return to the referent zone with p < 0.05. CONCLUSION The return of the IPS score to baseline occurred more rapidly in our series than what has previously been reported. The 1.2% incidence of transurethral resections also compares favorably with the published literature. We believe these results may be due to maintaining the average urethral dose to approximately 115% of the prescribed dose and the prophylactic and long-term use of alpha-blockers.

Seed fixity in the prostate/periprostatic region following brachytherapy

PURPOSE Although postoperative dosimetric analyses of prostate brachytherapy are commonly reported, the long-term persistence, or fixity, of seeds implanted in the prostate gland and periprostatic region remains unclear, with only a few reports regarding the loss or migration of the seeds in the implanted region and none which correlate lung embolization to pelvic seed loss. METHODS AND MATERIALS The study population consisted of 175 consecutive patients implanted with either 125I (95 patients) or 103Pd (80 patients) using a mean of 136 seeds in a modified uniform loading approach to cover a planning volume that was 1.64 times the ultrasound prostate volume. An average of 64% of 125I seeds were embedded in braided vicryl suture, and these seeds were used on the periphery and extra prostatic regions. Following CT-based dosimetric analysis on day 0, all patients had orthogonal plain films of the pelvis obtained from day 0 to day 502, with an average of 2.3 film pairs per patient. Routine diagnostic PA and lateral chest X rays were obtained for 156 patients over the same time period. RESULTS The mean pelvic seed fixity was greater than 98% throughout the time covered by this study. The seed fixity rates for 125I and 103Pd, although nearly equal, were significantly different up to 60 days post implant. The median 125I seed loss per patient was only 1 seed through 180 days while for 103Pd, the median seed loss was 2 seeds at 28 and 60 days and 3 seeds at 180 days. The fraction of patients experiencing no seed loss decreased from 40% at 28 days to 20% at 180 days for 125I and from 24% to 7% for 103Pd over the same time interval. Patient and treatment parameters closely correlated to local seed loss include the number of seeds implanted, the planning volume, and the number of loose seeds, and for 125I, the fraction of seeds in suture. The fraction of seeds placed outside the gland was not correlated with seed loss. Of the seeds lost from the pelvis, about 10% were found to embolize to the lungs. Among the 156 patients with post-implant chest X rays, the fraction of patients with pulmonary seed embolization was 34/156 (21.8%). Of the 20 patients who had post-implant chest X rays obtained within 14 days of brachytherapy, none had seeds detected in the lungs, while of the 136 patients who had chest X rays obtained greater than 30 days following implantation, 25.0% (34 patients) were noted to have seeds visualized in the lungs. CONCLUSIONS With a median follow-up of 9 months, 125I seeds embedded in a vicryl suture or 103Pd seeds can be safely implanted in the prostate and periprostatic tissue with a high probability of prostate bed seed fixity and a low incidence of radioactive seed embolization to the lungs.

Efficacy of sildenafil citrate in prostate brachytherapy patients with erectile dysfunction.

OBJECTIVES To ascertain the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction (ED) either before or after prostate brachytherapy by an open-label, nonrandomized study. METHODS Sixty-two patients who underwent prostate brachytherapy between March 1995 and July 1998, had ED either before or after brachytherapy, and were interested in treatment with sildenafil comprised the patient population. Clinical and treatment parameters evaluated for medication efficacy included patient age at brachytherapy and at medication administration, hypertension, diabetes, smoking history, onset of ED, potency status before implant, frequency of intercourse before brachytherapy (if potent), use of neoadjuvant hormonal manipulation, use of moderate dose external beam radiation therapy before implantation, choice of isotope, V100 (the percentage of the prostate volume receiving at least 100% of the prescribed minimal peripheral dose), and sildenafil dose. RESULTS Fifty (80.6%) of 62 patients responded favorably to sildenafil. None of the treatment parameters predicted medication failure, and among the clinical parameters, only diabetes predicted failure (3 of 5) and only with borderline statistical validity (P = 0.046). CONCLUSIONS Our results suggest brachytherapy-induced impotence is as amenable to sildenafil treatment as ED from other causes. In addition, our 80.6% success rate is comparable to reported results for patients who underwent bilateral nerve-sparing radical prostatectomy and significantly better than patients who underwent unilateral nerve-sparing or non-nerve-sparing approaches.

RECTAL DOSIMETRIC ANALYSIS FOLLOWING PROSTATE BRACHYTHERAPY

PURPOSE To retrospectively assess the rectal tolerance dose in transperineal ultrasound-guided prostate brachytherapy using easily measured point doses. METHODS AND MATERIALS Forty-five consecutive patients who underwent prostate seed implantation from January 1996 to October 1996, using either 125I or 103Pd as monotherapy or as a boost following 45 Gy of external beam radiotherapy (XRT), were evaluated. For monotherapy using 125I, the minimal peripheral dose (mPD) was 160 Gy, utilizing dosimetry parameters which are equivalent to 144 Gy under the American Association of Physicists in Medicine Task Group 43 (AAPM TG43) recommendations. Computed tomography (CT)-based dosimetry was performed within 9 days of the implant, with a urinary catheter in place for identification of the urethra, and a rectal obturator positioned prior to the CT scan for identification of the anterior rectal mucosa. Dosimetric parameters relevant to this study were the average, maximal and minimal anterior rectal mucosal dose, and the surface area and length of the anterior rectal mucosa irradiated to 50%, 75%, 90%, 100%, and 120% of the prescribed dose. Rectal complications were determined by patient reporting during office visits and telephone follow-up. Follow-up ranged from 19 to 28 months (median 23). RESULTS Among the four cohorts, the average anterior rectal mucosal dose as a percent of the prescribed mPD was 82.5% +/- 14.1% (standard deviation, SD), and the average maximum was 120% +/- 35%. The length of the rectum receiving a given dose was found to be correlated with the rectal surface area receiving that dose (r2 = 0.82 - 0.93 over the dose range 0.5-1.2 mPD). Rectal complications occurred in only four patients, and consisted of mild, self-limited proctitis. Three of the four were in the top quartile of average and maximal rectal dose and length of rectum receiving > or = 100% of mPD, while the fourth was in the bottom quartile of these parameters. In terms of surface area, all four patients were in the upper half of the study group, with > or = 90 mm2 at dose levels > or = 100% of mPD. CONCLUSION Our results indicate that in an implant program which maintains the anterior rectal mucosa point dose averages to about 85% of the prescribed dose (regardless of the choice of isotope or the treatment approach), the average maximum to 120% of mPD, and the length of the anterior rectal mucosa receiving 100% and 120% of the prescribed dose at approximately 10 mm and 5 mm, respectively, the incidence of mild self-limited proctitis will be in the range of approximately 9%, without incidence of rectal ulceration and/or fistula formation.

Potential role of various dosimetric quality indicators in prostate brachytherapy.

PURPOSE Postoperative CT-based dosimetric analysis provides detailed information regarding the coverage and uniformity of an implant, but the assessment of implant quality remains an unanswered and controversial issue. There is no disagreement that a good implant should cover the target volume with an adequate dose, but there is no consensus as to what represents an adequate dose. MATERIALS AND METHODS The American Brachytherapy Society has recently proposed that prostate brachytherapy quality be measured in terms of the following parameters: D90, V100, and V150 where D90 is defined as the minimal dose covering 90% of the prostate volume and V100 and V150 are defined as the percent volume of the prostate receiving at least 100% or 150% of the prescribed minimal peripheral dose (mPD), respectively. We report detailed day 0 dosimetric evaluation for 60 consecutive prostate brachytherapy patients implanted via a standard transperineal ultrasound guided approach in terms of D90, D100, V90, V100, and V150 and also the maximal and average rectal and urethral dose. RESULTS Dosimetric evaluation resulted in a V100 greater than 80% of the prostate volume and a D90 greater than 90% of the mPD in the entire patient population. There was a statistically significant difference between the quality scores of 125I implants and 103Pd implants with the 125I mean V100 and D90 at 95.3% volume and 109.9% mPD, respectively, vs. 103Pd at 91.8% volume and 103.7% mPD. Likewise, the rectal and urethral doses as a fraction of mPD were significantly lower in 103Pd than in 125I implants. This occurred despite the fact that palladium implants were typically preplanned with significantly better coverage and hotter V150 than iodine implants. We consider V150 to be an important parameter for determining dose homogeneity although the clinical utility of dose homogeneity remains unknown. The mean V150 was 45.6 +/- 9.6% volume. There was no additional dosimetric utility from a determination of V90 while D100 was found to be overly sensitive to steep dose gradients at the periphery of the prostate. CONCLUSIONS This report represents the first detailed postimplant day 0 dosimetric evaluation comparing ABS recommended quality parameters used to evaluate prostate brachytherapy. At the present time, no long-term clinical outcomes are available because of short follow-up. As PSA based follow-up data becomes available, however, this report may help define what represents an adequate implant.

A comparison of radiation dose to the neurovascular bundles in men with and without prostate brachytherapy-induced erectile dysfunction

PURPOSE The etiology of erectile dysfunction after definitive local therapy for carcinoma of the prostate gland represents a multifactorial phenomenon including neurogenic compromise, venous insufficiency, local trauma, and psychogenic causes. It has been suggested that impotence after prostate brachytherapy is a consequence of excessive radiation dose to the neurovascular bundles (NVB). Herein we evaluate the potential relationship between radiation dose to the NVB and the development of erectile dysfunction following prostate brachytherapy. METHODS AND MATERIALS The radiation dose to the NVB was evaluated for 33 patients who developed erectile dysfunction (ED) following brachytherapy plus 21 additional patients who were potent before and subsequent to brachytherapy. Of the 54 patient study group, the median follow up was 37 months, and 25 patients were managed with (125)I as a monotherapeutic approach and 29 received (103)Pd as a boost following 45 Gy of external beam radiation therapy. Radiographic localization of the NVB was performed via a two-dimensional geometric model that placed 3-NVB calculation points on the left and right posterolateral side of each 5-mm CT slice. Parameters evaluated included dose-surface histograms, dose parameters via point doses on each slice, the magnitude of the dose in relationship to the distance from the base, and the relationship between NVB radiation dose in patients with and without ED, patient response to sildenafil and case sequence number. RESULTS In terms of percent prescribed minimum peripheral dose (% mPD), there was no significant difference in mean neurovascular bundle dose between potent and impotent patients, between the isotopes ((125)I or (103)Pd), mono- or boost therapy, or side of the prostate for which the overall average was 217% +/- 55% of mPD. There was also no significant dosimetric difference in terms of response to sildenafil based on a multivariate analysis which included % mPD and various dose thresholds and side of the gland. The dose distribution over the length of the prostate rose smoothly from the base and apex to peak at midgland in (125)I implants while (103)Pd implants had a relatively constant dose over the length of the prostate. Considering the calculation grid as forming a 6-mm wide ribbon along each side of the prostate, the average patient had 70 mm(2) area receiving at least 300% of mPD. CONCLUSION In this study, no relationship between radiation dose to the NVB and the development of post brachytherapy erectile dysfunction was discernible. Such a difference may become evident with additional follow-up. If long-term brachytherapy-induced erectile dysfunction is related to the radiation dose to the NVB, the ultimate preservation of potency following prostate brachytherapy may be markedly inferior to what has been reported. Nevertheless, the majority of this patient population responded favorably to sildenafil.

Comparison of seed loading approaches in prostate brachytherapy

Since uniform seed loading in prostate brachytherapy can produce an intolerably high dose along the urethra, some form of peripheral loading is commonly employed. We define three variants of peripheral loading and compare them in a small, medium, and large prostate in terms of coverage of the planning target volume (PTV), homogeneity, and ability to spare critical structures of excessive dose. Modified uniform loading has at least 2/3 of the seeds occupying sites on a 1 cm cubic grid keyed to the prostate base and the posterior border of the prostate. Nonuniform loading explicitly spares the urethra by using only basal and apical seeds in at least two centrally located needles. Peripheral loading uses higher activity seeds with the posterior implant plane 5 mm anterior to the posterior border of the prostate. The three prostate volumes (18.7, 40.7, and 60.2 cm3 by ultrasound) were expanded to planning volumes (32.9, 60.0, and 87.8 cm3, respectively). The planning volumes (PTVs) were loaded with a 125I seed distribution and activity sufficient to cover 99.7+/-0.3% of the PTV with the prescribed minimal peripheral dose (mPD) of 145 Gy. Activities used ranged from 0.32 to 0.37 mCi/seed (0.41-0.47 U/seed) for the first two approaches and from 0.57 to 0.66 mCi (0.72-0.84 U) for peripheral loading. Modified uniform loading produced the most uniform distribution based on dose-volume histograms and the volume receiving >150% of prescribed dose. All the approaches are capable of constraining the superior-inferior dose profile (the urethral path) to less than 150% of the mPD, but the nonuniform approach with explicit urethral sparing kept the urethral dose below 120% of the mPD. Dose profiles for the three approaches along the posterior-anterior midline axis are comparable near the urethra, but peripheral and nonuniform approaches have extended regions where the dose is >150% of mPD. These regions approach within 10 mm of the rectum or urethra, so these two approaches require greater accuracy in intraoperative execution of the plan. Although each of the three planning approaches can achieve the treatment goals of adequate coverage and critical structure sparing, modified uniform loading has a more homogeneous dose distribution. This approach may be more forgiving of systematic errors in seed placement.

Influence of timing on the dosimetric analysis of transperineal ultrasound-guided, prostatic conformal brachytherapy

Postoperative computed tomography (CT)-based dosimetric analysis of transperineal ultrasound-guided conformal prostate brachytherapy provides detailed information regarding the coverage and uniformity of the implant. However, there is no generally accepted standard for the optimal timing of the postoperative dosimetry. This report details dosimetric analysis and the effect of timing based upon CT and orthogonal film evaluation for ten unselected patients implanted with either iodine-125 (125I) or palladium-103 (103Pd). Within 2 hours after implantation, patients underwent a CT scan and the first of four sequential sets of orthogonal films. Subsequent orthogonal films were obtained on days 3, 14, and 28 postimplant. CT-based dosimetry revealed coverage of the prostate to the prescribed minimal peripheral dose (mPD) at 93.1 +/- 3.6% of the volume, the prostate volume receiving 150% of mPD was 38.2 +/- 8.7%, and the urethral and rectal doses were 114 +/- 12% and 78 +/- 19% of mPD, respectively. The implanted seeds seen on orthogonal films acted as markers for temporal changes in prostate dimensions, and the standard deviation of each dimension was used as input in an ellipsoidal volume calculation. Seed coordinates were self normalized to the center of gravity of each two-dimensional view and were measured relative to the linear regression line in the superior-inferior direction. The reproducibility of the anteroposterior (AP) film setup in terms of temporal variation in the angle of the regression line was markedly better than that of the lateral films, 1.8 degrees +/- 1.2 degrees vs. 4.3 degrees +/- 2.6 degrees, respectively. Dimensional contraction from day 0 to day 28 averaged 11.3% in the superior-inferior direction, 8.5% in the AP/PA (posteroanterior) direction, and 2.5% in the right-left lateral direction. This translated into a volume change of 20.9% (ranged 11.6-31.6%), which was determined by using the ellipsoid method. The half-life for edema resolution was 10.6 +/- 1.8 days (range 8.6-14.3 days). However, because of variability in the degree and extent of edema and its rate of resolution, we believe that it may be futile to define a single point in time as the most accurate indicator of the postoperative dose distribution. Rather, it may be preferable to accept universal standardization of timing and methodology for CT-based postoperative dosimetry, which would facilitate comparison of results between centers and maximize the information content of that single measurement. We conclude that day 0 represents the optimal time, because dosimetric evaluation at that time minimizes patient discomfort and inconvenience (a catheter is already in place), provides information about edema when it is near its maximum extent, and provides prompt closure of the learning loop and, as such, hopefully will result in improved implantation techniques and results.

The dependence of prostate postimplant dosimetric quality on CT volume determination

PURPOSE The postoperative evaluation of permanent prostate brachytherapy requires a subjective determination of the implant volume. This work investigates the magnitude of the effect that various methods of treatment volume delineation have on dosimetric quality parameters for a treatment planning philosophy that defines a target volume as the prostate with a periprostatic margin. METHODS AND MATERIALS Eight consecutive prostate brachytherapy patients with a prescribed dose of 145 Gy from 125I as monotherapy comprised the study population. The prostate ultrasound volume was enlarged to a planning volume by an average factor of 1.8 to encompass probable extracapsular extension in the periprostatic region. For this cohort, the mean pretreatment parameters were 30.3 cm3 ultrasound volume, 51.8 cm3 planning volume, 131 seeds per patient, and 42.9 mCi total activity. On CT study sets obtained less than 2 hours postoperatively, target volumes were drawn using three methods: prostate plus a periprostatic margin, prostate only which excluded the puborectalis muscles, the periprostatic fat and the periprostatic venous plexus, and the preplanning ultrasound magnified to conform to the magnification factor of the postimplant CT scan. Three sets of 5 dosimetric quality parameters corresponding to the different volumetric approaches were calculated: V100, V150, and V200 which are the fractions of the target volume covered by 100, 150, and 200% of the prescribed dose, and D90 and D100, which are the minimal doses covering 90 and 100% of the target volume. RESULTS The postoperative CT volume utilizing the prostate plus margin technique was comparable to the initial planning volume (mean 55.5 cm3 vs. 51.8 cm3, respectively) whereas those determined via superimposing the preplan ultrasound resulted in volumes nearly identical to the initial ultrasound evaluation (mean 32.4 cm3 vs. 30.3 cm3). The prostate only approach resulted in volumes approximately 25% larger than the ultrasound volume approach. Despite the volume determinations being markedly different, no significant differences between the approaches were appreciated for V100, V150, V200, and D90. Large variations seen in D100 were uncorrelated to any of the other parameters and make D100 unsuitable as a quality indicator. CONCLUSIONS In terms of a logarithmic measure, the variation between volumetric approach for V100, V150, V200, and D90 was less than one-fifth the variation of the CT volumes. These results which indicate relative independence of postimplant CT volume determination and dosimetric quality are only valid for a planning philosophy that includes the prostate with a periprostatic margin as the target volume.

Rectal function following prostate brachytherapy.

PURPOSE Quality of life following therapeutic intervention for carcinoma of the prostate gland has not been well documented. In particular, a paucity of data has been published regarding bowel function following prostate brachytherapy. This study evaluated late bowel function in 209 consecutive prostate brachytherapy patients via a one-time questionnaire administered 16-55 months postimplant. MATERIALS AND METHODS Two hundred nineteen consecutive patients underwent permanent prostate brachytherapy from April 1995 through February 1998 using either (125)I or (103)Pd for clinical T1c-T3a carcinoma of the prostate gland. Of the 219 patients, 7 had expired. Of the remaining 212 patients (median follow-up, 28 months), each patient was mailed a self-administered questionnaire (10 questions) with a prestamped return envelope; 209 (98.6%) surveys were returned. Clinical parameters evaluated for bowel dysfunction included patient age, diabetes, hypertension, history of tobacco consumption, clinical T-stage, elapsed time since implant, and prostate ultrasound volume. Treatment parameters included utilization of neoadjuvant hormonal manipulation, utilization of moderate dose external beam radiation therapy prior to implantation, choice of isotope ((125)I vs. (103)Pd), rectal dose (average, median and maximum doses), total implanted seed strength, values of the minimum dose received by 90% of the prostate gland (D(90)), and the percent prostate volume receiving 100%, 150%, and 200% of the prescribed minimum peripheral dose (V(100), V(150) and V(200), respectively). Because detailed baseline bowel function was not available for these patients, a cross-sectional survey was performed in which 30 newly diagnosed prostate cancer patients of comparable demographics served as controls. RESULTS The total rectal function scores for the brachytherapy and control patients were 4.3 and 1.6, respectively, out of a total 27 points (p < 0.001). Of the evaluated clinical parameters, only the preimplant number of bowel movements per day were correlated with the total survey score (p < 0.01). None of the treatment parameters were significantly correlated with the total survey score. Despite the fact that implantation with (103)Pd resulted in lower radiation doses to the rectum, the choice of isotope was not predictive of bowel function scores. A trend toward increased rectal scores was noted for older patients, and a nonsignificant improvement in rectal survey scores was noted with elapsed time from implantation. Only 19.2% (40/208) of the treatment group reported a worsening of bowel function following implantation. Patient perception of overall rectal quality of life, however, was inversely related to the utilization of external beam radiation therapy (p = 0.034). CONCLUSION To date, no severe changes in late bowel function have been noted following prostate brachytherapy. Although the survey scores indicate bowel function is worse after an implant, the minor changes are not significant enough to bother most individuals. Less than 20% of patients reported that their bowel function was worse following prostate brachytherapy.