Brachytherapy
Volume 10, Issue 1 , Pages 35-43, January 2011

Postimplant rectal dosimetry is not dependent on 103Pd or 125I seed activity

  • Gregory S. Merrick

      Affiliations

    • Schiffler Cancer Center & Wheeling Jesuit University, Wheeling, WV
    • Corresponding Author InformationCorresponding author. Schiffler Cancer Center, 1 Medical Park, Wheeling, WV 26003. Tel.: +1-304-243-3490; fax: +1-304-243-5047.
    • ,
  • John Sylvester

      Affiliations

    • Seattle Prostate Institute, Seattle, WA
    • ,
  • Peter Grimm

      Affiliations

    • Seattle Prostate Institute, Seattle, WA
    • ,
  • Zachariah A. Allen

      Affiliations

    • Schiffler Cancer Center & Wheeling Jesuit University, Wheeling, WV
    • ,
  • Wayne M. Butler

      Affiliations

    • Schiffler Cancer Center & Wheeling Jesuit University, Wheeling, WV
    • ,
  • Joshua L. Reed

      Affiliations

    • Schiffler Cancer Center & Wheeling Jesuit University, Wheeling, WV
    • ,
  • Jonathan Khanjian

      Affiliations

    • Seattle Prostate Institute, Seattle, WA

Received 24 September 2009; received in revised form 3 December 2009; accepted 8 December 2009. published online 12 February 2010.

Article Outline

Abstract 

Purpose

In this study, the effect of prostate brachytherapy seed activity on postimplant rectal dosimetry was evaluated in Pro-Qura (Prostate Brachytherapy Quality Assurance; Seattle, WA) proctored, community-based programs.

Methods and Materials

Twenty-three hundred patients (1563 iodine-125 [125I] and 737 palladium-103 [103Pd]) from 78 brachytherapists with postimplant rectal dosimetry were identified. Seed activity was stratified into three tertiles for each isotope (≤0.300, 0.301–0.326, and >0.326mCi/seed for 125I and ≤1.330, 1.331–1.547, and >1.547mCi/seed for 103Pd). Postimplant dosimetry was performed in a standardized fashion. The rectum was contoured by outlining the outer rectal wall. The volume of the rectum receiving 100% of the prescription dose (R100) was calculated in cubic centimeters. The prostate V100 and D90 volumes were also calculated.

Results

The mean prostate volume was 35.8 and 32.3cm3 for 125I and 103Pd. The median time to postimplant CT was 30 days. For 125I, the V100 increased from 91.0% to 93.7% (p=0.012) and the D90 increased from 105.9% to 108.7% (p<0.001) for the lowest to the highest 125I seed activities. In contrast, no significant changes in V100 (p=0.751) or D90 (p=0.200) were discerned when stratified by seed activity. For both isotopes, there was no correlation between seed activity and R100, and R100 was highest for the intermediate seed activities. Overall, the R100 was lower for 103Pd vs. 125I (0.63 vs. 0.82cm3, p<0.001).

Conclusions

Within the confines of seed activities used in this study, higher activity seeds did not result in a deleterious effect on rectal dose. Higher activity seeds were associated with improved prostate dosimetry for 125I, whereas 103Pd dosimetry was not dependent on seed activity.

Keywords: Prostate brachytherapy, Rectal dose, Seed strength, Dosimetry

 

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Introduction 

Although brachytherapy-related rectal morbidity has declined over time, serious rectal complications remain the most dreaded outcome of brachytherapy and constitute most of the brachytherapy-related medical litigation [1], [2]. Although typical rectal complications after brachytherapy consist of mild, self-limited proctitis in 4–11% of patients, serious rectal bleeding and/or ulceration occasionally progresses to prostatorectal fistula [3], [4]. Refinements in implantation technique, establishment of postimplant dose thresholds for normal tissue tolerance, and improved ultrasound imaging have contributed to improved rectal function after brachytherapy [5], [6].

There is no consensus in the brachytherapy community regarding whether higher seed activity is associated with better prostate dosimetry and/or higher doses to normal surrounding structures, including the rectum. In 1995, Wallner et al. (7) reported that rectal bleeding and ulceration were associated with greater rectal doses; however, no relationship was discerned between source activity or total implant activity and long-term morbidity. In a randomized trial of high- vs. low-source strength iodine-125 (125I), higher activity seeds improved prostate coverage with no statistically significant differences in rectal or urethral doses (8).

In contrast, a theoretical study evaluating the effect of random seed placement in 125I implants suggested that placement errors with higher activity seeds result in significantly greater doses to the urethra (9). Although theoretical doses to the rectum were not calculated, the authors concluded that there would be a higher probability of unfavorable target coverage because of random seed placement error when using 125I seeds >0.35mCi activity. In a comparable study, treatment plans were designed for 125I and palladium-103 (103Pd) of varying seed activities (10). The external volume index (i.e., the amount of healthy tissue receiving at least the prescription dose as a percentage of the target volume) was substantially lower for both isotopes with lower activity seeds. However, over the range of seed activities simulated, the external volume index of 103Pd was lower than 125I. The authors concluded that higher seed activities might result in higher doses to the rectum with both isotopes.

Pro-Qura (Prostate Brachytherapy Quality Assurance; Seattle, WA) was established as a quality initiative to standardize pre- and postimplant dosimetry and to facilitate dosimetry comparisons across institutional and community practices (11). Consistent external feedback was expected to improve biochemical control rates and decrease brachytherapy-related morbidity. In a prior evaluation of the Pro-Qura database, we demonstrated that the volume of the rectum receiving 100% of the prescription dose (R100) decreased with brachytherapy experience (12). It has been reported that maintaining the Day 0 R100 below 1.0cm3 results in a proctitis rate below 2% (13). In addition, limiting the Day 0 R100 to <0.5cm3 reduced the prostatorectal fistula rate to less than 1 in 900 (14).

In this study, the effect of prostate brachytherapy seed activity on postimplant rectal dosimetry in 103Pd and 125I implants was evaluated in Pro-Qura proctored, community-based brachytherapy programs.

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Methods and materials 

From February 2002 to December 2008, 2300 patients were implanted with permanent, low–dose rate brachytherapy seeds by a cohort of 78 brachytherapists actively participating in Pro-Qura. Their postimplant computed tomography (CT) scans were evaluated for prostate and rectal dosimetry from March 2002 to December 2008. The median number of implants per brachytherapist was 29.5±44.7 (median, 15; range, 1–308). Patients implanted at the authors' institutions are not part of the Pro-Qura database.

For 125I implants, 73.6% of patients were prescribed a monotherapy dose of 145Gy and 5.7% of patients were prescribed 144Gy. The predominant boost therapy dose of 110Gy was used in 19.8% of patients, whereas the remaining 1% of patients received boost dose prescriptions between 100 and 120Gy. For 103Pd, the only monotherapy dose prescribed was 125Gy in 68.7% of patients, but boost dose prescriptions were nearly evenly divided between 100 (16.0%) and 90Gy (14.8%). The remaining 0.5% of patients received other boost dose prescriptions between 94 and 115Gy.

To compare dosimetric outcomes as a function of seed strength without bias when a variety of monotherapy and boost therapy doses were prescribed, seed strengths were normalized to a monotherapy equivalent after the implant dosimetry was evaluated. Consider the relative dose–volume histogram (DVH) for an implant using a given source model and strength to deliver some prescribed dose. That seed distribution can be used to produce an identical relative DVH for any other prescribed dose if the seed strength is changed by the ratio of the new prescribed dose to the original prescribed dose. In this study, the seed strengths used were adjusted for comparative purposes by the relation:

(1)

The standard monotherapy prescribed dose was assigned as 145Gy for 125I and 125Gy for 103Pd. In this way, implants using seeds that were relatively “hot” for a prostate brachytherapy boost can be fairly compared with implants that used seeds that were relatively hot for monotherapy. For example, a solitary 0.33-mCi 125I seed in the rectal wall will cover 5mm3 of rectum to the prescribed dose of 145Gy. That same seed will cause the same rectal volume damage if the prescribed dose is 110Gy and the activity is 0.25mCi, which is the monotherapy activity times the dose ratio 145/110Gy. Likewise, a monotherapy implant seed that is 20% hotter than the mean activity will produce identical rectal damage to a seed from any boost prescription dose if its adjusted activity is 20% hotter than the adjusted mean activity.

Seed activity was stratified into three tertiles for each isotope (Table 1). The tertiles in each isotope group were bounded by the activity values, which divided the group into nearly three equal subgroups. The cut points were adjusted so that all patients with a given activity fell completely within one and only one tertile, which resulted in tertiles of unequal numbers. For 125I, seed activity stratification was below 0.319, 0.319 to 0.336, and ≥0.336mCi per seed. For 103Pd, the seed activity stratification was <1.410, 1.410 to 1.547, and ≥1.547mCi per seed, respectively. Although these monotherapy equivalent seed activity ranges are characteristic of the Pro-Qura population, they should not be taken as definitive of low and high activity in any other prostate brachytherapy context.

Table 1. Categorical treatment parameters stratified by adjusted seed activity groups and isotope for the 2300 patients
Adjusted seed activity group (mCi/seed)Adjusted seed activityNumber of patientsNumber of brachytherapistsaMonotherapyActual seed activity (mCi/seed)Boost therapyActual seed activity (mCi/seed)
Mean±SDCount (%)Mean±SDCount (%)Mean±SD
125I
<0.3190.299±0.02151749476 (38.4)0.298±0.02241 (12.7)0.233±0.010
0.319–0.3360.327±0.00552247407 (32.8)0.325±0.005115 (35.5)0.250±0.002
≥0.3360.368±0.03952442356 (28.7)0.367±0.036168 (51.9)0.278±0.034
pb <0.001
Overall0.331±0.0381563671239 (79.3)0.327±0.037324 (20.7)0.263±0.030

103Pd
<1.4101.308±0.09623921162 (32.0)1.307±0.10877 (33.3)0.981±0.050
1.410–1.5471.503±0.03818329108 (24.8)1.496±0.03675 (32.5)1.186±0.058
≥1.5471.630±0.12931531236 (42.7)1.613±0.11979 (34.2)1.269±0.111
pb 0.001
Overall1.494±0.17273737506 (68.7)1.490±0.168231 (31.3)1.146±0.145

SD=standard deviation.

aThe total number of brachytherapists was 78. The numbers in the columns do not add to either 78 or the overall numbers because many brachytherapists were represented in more than one activity group and some use one radionuclide exclusively.

bp-Values determined by Pearson chi-square for the distribution of patients between monotherapy and boost therapy.

Another subgroup analysis was based on the number of procedures performed per brachytherapist. There have been many studies correlating outcomes of various surgical procedures to the institutional and individual surgeon experience (15). Better radical prostatectomy outcomes have been associated with high individual surgeon annual volume thresholds ranging from 10 to 40 patients per year (16). In this study, we split the patient population into nearly two equal groups according to the number of implants performed by the brachytherapist, and we defined a high-volume brachytherapist (HVB) as one who had implanted 50 or more patients.

Postimplant dosimetry was performed in a standardized fashion by overlapping the preimplant ultrasound and postimplant CT. The technique was developed by Pro-Qura and has previously been reported in detail [11], [12]. Postimplant CT scans were obtained at a mean and median of 29.3±12.3 days and 30 days, respectively. Rectal doses were calculated based on CT rectal contours. The entirety of the outer rectal wall was contoured, extending 1cm above the base and below the apex of the prostate, and evaluated for dose. Rectal dose was defined in terms of the volume of the rectum in cubic centimeters receiving 100% of the prescription dose (R100). Criteria for postimplant rectal dosimetry adequacy were a R100≤1.0cm3 for early dosimetry (Day 0–14 postimplant CT) and a R100≤1.3cm3 for late dosimetry (Day 15–50 postimplant CT) [13], [17]. Doses exceeding these cut points were shown to increase the risk of Radiation Therapy Oncology Group (RTOG) Grade 2 or greater rectal morbidity. Pro-Qura criteria for postimplant prostate dosimetric adequacy included a V100 above 80% and a D90 of 90% to 140% of the minimum prescribed peripheral dose for both 103Pd and 125I. If any of the prostate or rectal criteria did not meet minimum standards, the implant was deemed inadequate. All cases were preplanned. There is no data on ad hoc intraoperative changes to the plans. The attending brachytherapist received Pro-Qura recommendations regarding implant techniques to improve prostate and rectal dose distributions. The patient database contains no information regarding any supplemental therapy offered by brachytherapists to patients with suboptimal prostate dosimetry or prophylactic measures used in patients at risk for rectal morbidity.

Pearson's chi-square test was applied to determine differences in population distributions. One-way analysis of variance tests were performed to determine the significance of the differences in mean clinical and dosimetric parameters across seed strengths. Linear regressions were applied to scatter plot data to determine the correlation between seed strength and R100. Univariate and multivariate regression analysis was used to identify predictors of binary categorical outcomes. All data were analyzed using Predictive Analytics Software, version 17.0 (SPSS, Chicago, IL). Statistical significance was set at a p≤0.05 for all analyses except for selection of predictors in multivariate regression analysis, where a threshold of less than 0.10 was used.

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Results 

Twenty-three hundred postimplant CT scans from 78 Pro-Qura affiliated brachytherapists were evaluated for prostate and rectal dosimetry. Of the 78 brachytherapists, 41 of the 67 125I users used that radionuclide exclusively, whereas 11 of the 103Pd users implanted exclusively with that radionuclide. Twenty-six brachytherapists used both radionuclides in their practice. The mean and median days between implant and postimplant CT were 29.3±12.3 and 30 days, respectively. Table 1 summarizes the number of cases by seed activity (stratified by tertiles). 125I was used substantially more often than 103Pd (1563 vs. 737 cases) and for both isotopes monotherapy cases far outnumbered boost brachytherapy. The dispersion of monotherapy dose adjusted seed strengths was greater for 103Pd than 125I. The mean of the high activity tertile was 25% higher than the lowest tertile for 103Pd, whereas for 125I the range was 23% from low to high.

The distribution of patients between monotherapy and boost differed significantly according to adjusted dose tertiles for each isotope. Most of the 125I boost patients (51.9%) were in the high tertile, whereas the low tertile for monotherapy patients had a slight excess of patients (38.4%). The 103Pd boost patients were evenly distributed among the adjusted seed activity groups, but the higher activity group was disproportionately populated by the monotherapy patients (42.7%).

From our definition of a HVB as one who had implanted 50 or more patients in this study, 12 of the 78 brachytherapists were of high volume and accounted for 55% of the patients evaluated. For the entire study population, there was no significant difference between adjusted seed activity used by HVBs and low-volume brachytherapists, but HVBs had significantly lower R100 values, 0.67 vs. 0.87cm3, and significantly higher V100, V150, and D90 values (Table 2). When further stratified by isotope, the HVBs used significantly higher adjusted mean 125I activity, had significantly higher V100 and D90 values, and significantly lower R100 values (Table 2). For 103Pd users, the HVBs used significantly lower mean 103Pd seed activity, and the HVBs had significantly higher D90 values. The V100 and R100 values for 103Pd users were not significantly different based on patient case volume.

Table 2. Continuous dosimetric parameters stratified by high and low brachytherapist case volume and isotope
Radio-nuclideBrachytherapist volumeaNumber of patientsAdjusted seed activity (mCi)V100 (% vol)V150 (% vol)D90 (% mPD)R100 (cm3)
Mean±SDMean±SDMean±SDMean±SDMean±SD
BothLow10350.69±0.5689.1±9.450.1±15.6102.8±15.90.87±1.01
High12650.72±0.5590.6±9.352.0±14.9106.4±19.10.67±1.03
pb0.112<0.0010.003<0.001<0.001

125ILow7270.33±0.0489.8±9.248.3±16.3104.5±15.50.94±1.09
High8360.34±0.0491.7±7.849.0±14.4107.6±16.00.73±0.76
pb<0.001<0.0010.328<0.001<0.001

103PdLow3081.53±0.1587.4±9.654.5±12.698.9±16.30.71±0.79
High4291.47±0.1888.4±11.457.7±14.2104.1±23.70.57±1.41
pb<0.0010.2080.0010.0010.123

SD=standard deviation; mPd=minimum prescribed peripheral dose.

aLow-volume brachytherapists performed less than 50 implants, whereas high-volume brachytherapists performed 50 implants or more.

bp-Values determined two-sided t test.

Table 3 summarizes dosimetric outcome stratified by isotope and seed activity. For 125I, there was a statistically significant difference in prostate volume, specific activity, the prostate dosimetric quality indices, and rectal dose when stratified by seed activity. Those patients implanted with the highest activity seeds (>0.335mCi/seed) had statistically higher V100 and D90 values (p<0.001). Although the difference between adjusted activity tertiles was significant for R100, the highest rectal doses were documented in those patients with intermediate 125I seed activities (R100: 0.83, 0.91, and 0.73cm3 for low, intermediate and higher activity tertiles, respectively). The lowest activity tertile for both isotopes also had the lowest specific activity implanted as millicuries per cubic centimeter. For 103Pd, there was no significant difference between adjusted seed activity tertiles and prostate volume (V100). There was seed activity dependence for 103Pd implants, with the lowest adjusted seed activity group having the highest D90. Consistent with 125I, there was a significant difference between activity groups for R100, but here there was a trend for higher rectal doses with higher 103Pd seed activities (R100: 0.42, 0.63, and 0.78cm3 for low, intermediate, and higher activity tertiles, respectively). When comparing 125I with 103Pd, the mean R100 was lower in the 103Pd group, 0.63±1.19cm3 vs. 0.82±0.93cm3 for 125I (p<0.001). The reverse order held true for the prostate V100 and D90 values. The relationship between seed activity, rectal dose, and the comparisons between 125I and 103Pd were not influenced by the timing of the postimplant CT.

Table 3. Continuous dosimetric parameters stratified by adjusted seed activity groups and isotope
Seed activity group (mCi/seed)Prostate volume (cm3)Specific activity (mCi/cm3)V100 (% vol)D90 (% mPD)R100 (cm3)Days to CT
Mean±SDMean±SDMean±SDMean±SDMean±SDMean±SD
125I
<0.31938.0±10.40.84±0.1789.4±9.7104.2±17.50.83±0.9728.7±12.7
0.319–0.33536.1±10.20.91±0.2189.9±8.3103.4±14.70.91±0.9328.2±18.7
≥0.33533.7±9.21.30±0.2293.1±7.0110.8±14.30.73±0.8928.8±9.2
pa<0.001<0.001<0.001<0.0010.0090.794
Overall35.9±10.10.93±0.2190.8±8.6106.1±15.90.82±0.9328.5±14.1

103Pd
<1.41031.2±9.64.18±0.9588.5±12.5104.9±26.40.42±0.5132.6±5.4
1.410–1.54732.1±9.54.82±0.9988.2±8.6100.4±16.80.63±1.6929.6±5.6
≥1.54733.3±10.54.80±0.9387.5±10.3100.6±18.50.78±1.1830.2±8.0
p0.055<0.0010.5360.0330.001<0.001
Overall32.3±10.04.60±0.9988.0±10.7101.9±21.10.63±1.1930.8±6.8

SD=standard deviation; mPd=minimum prescribed peripheral dose.

ap Values determined by one-way analysis of variance.

The elapsed days from implant to CT was significantly different between the activity groups for 103Pd, but the difference was not clinically significant. What may be significant is the effect of implant trauma and radiation edema and the postoperative dosimetry values. Although the maximum amount of edema and its duration are patient-specific, the reported ranges of each have been used by Chen et al. (18) to create a rigorous model that sets limits on the range of dosimetry errors as a function of time since implant. These results were incorporated into American Association of Physicists in Medicine recommendations of the optimum time for postimplant CT to minimize the dosimetry errors (19). The recommended postimplant dosimetry time for 125I is 1 month±1 week and for 103Pd it is 16±4 days. Because the dosimetry CT was obtained at about 1 month postimplant for both radionuclides, comparisons involving 103Pd have diminished validity.

Fig. 1, Fig. 2 are scatter plots of R100 vs. adjusted seed activity for 125I and 103Pd. For both isotopes, there is substantial scatter without any correlation (R2<0.01) between higher activity seeds and higher rectal doses. The total equivalent seed activity was calculated from the number of seeds implanted and the monotherapy dose adjusted seed activities. For 125I, the mean was 31.8±6.4mCi, and for 103Pd, the mean total activity was 143.0±34.2mCi. For both isotopes, total activity implanted increased significantly from one tertile to the next. Fig. 3, Fig. 4 plot R100 vs. total adjusted activity for 125I and 103Pd. As with the individual seed activity plots, the total activity showed negligible correlation with rectal dose.

  • View full-size image.
  • Fig. 1 

    Seed strength adjusted to monotherapy prescription dose vs. R100 for 1,563 125I cases. The vertical lines denote the tertile boundaries of 0.319 mCi and 0.335 mCi. The linear regression line shows virtually no correlation.

  • View full-size image.
  • Fig. 2 

    Seed strength adjusted to monotherapy prescription dose vs. R100 for 737 103Pd cases. The vertical lines denote the tertile boundaries of 1.270 mCi and 1.540 mCi. The linear regression line shows virtually no correlation.

Table 4 summarizes dosimetric inadequacies based on isotope and seed activity. For 125I, an inadequate R100 (>1.0cm3 for early dosimetry and >1.3cm3 for late dosimetry) was found in 22.2%, 26.4%, and 14.7% of the patients with low, intermediate, and higher seed activities, respectively. For 103Pd, an inadequate R100 was noted in 6.3%, 10.4%, and 17.1% of patients with low, intermediate, and higher seed activities. For both isotopes, the difference in distribution of inadequate R100 between activity tertiles was statistically significant, p<0.001. Overall, for each isotope group, an inadequate R100 was noted in 21.1% of 125I and 11.9% of 103Pd patients. Prostate dosimetric inadequacy was defined by deficiency in either prostate V100<80% or prostate D90<90%. By these criteria, 13.1% of 125I implants and 22.9% of 103Pd implants had inadequate prostate dosimetry. Overall implant inadequacy was defined as either R100 or prostate dosimetry inadequacy. For 125I and 103Pd, 31.8% and 32.3% of patients were found to have inadequate implants. Implant inadequacy for 103Pd was more likely a result of inadequate prostate coverage vs. rectal dosimetry, whereas the converse was true for 125I implants.

Table 4. Dosimetric inadequacies and their relationship to seed activity
Adjusted seed activity group (mCi/seed)R100 inadequateProstate dosimetry inadequateOverall implant inadequate
Count (%)aCount (%)aCount (%)a
125I
<0.31911522.28316.118535.8
0.319–0.33513826.48416.120439.1
≥0.3357714.7387.310820.6
pb<0.001<0.001<0.001
Overall33021.120513.149731.8

103Pd
<1.410156.34518.85824.3
1.410–1.5471910.44524.66133.3
≥1.5475417.17925.111937.8
pb<0.0010.1840.003
Overall8811.916922.923832.3

R100 inadequacy was defined as >1.0cm3 for cases with CT scans within 15 days of implant and >1.3cm3 otherwise. Overall implant inadequacy was defined as any of the following: inadequate R100, V100<80%, or D90<90%.

aPercentage of inadequate implants within each seed strength group.

bp-Value determined by Pearson chi-squared test comparing distribution of adequate vs. inadequate.

The difference in distribution of inadequate implants between activity tertiles was statistically significant for each isotope in the basis of R100 and overall implant dosimetry, but the difference in distribution of prostate dosimetry inadequacy was significant only in 125I implants. When stratified by monotherapy vs. boost therapy, the percentage of R100 inadequate 125I implants was 22.0% and 17.6%, respectively. For 103Pd, the percentage of R100 inadequate implants was 12.8% and 10.0% for monotherapy and boost therapy, respectively. The prostate dosimetry inadequate 125I implants were 14.3% and 8.6% for monotherapy and boost therapy, respectively, and for 103Pd, the percentages were 23.7% and 21.2%. For the three inadequacy classifiers, monotherapy implants failed more frequently than boost implants. When monotherapy and boost therapy implants were further stratified by activity tertiles, the distribution of inadequate implants was significantly different for monotherapy R100 and overall implant inadequacy for both isotopes and for monotherapy prostate dosimetry of 125I implants. There was no significant difference in the distribution of inadequate implants among boost implants for any dosimetric trigger for either isotope.

The univariate and multivariate predictors of inadequate R100 and inadequate prostate dosimetry are listed in Table 5. In multivariate analysis, inadequate R100 in 125I implants was predicted by seed strength group, prostate volume, D90 and V200. For 103Pd implants, seed strength group was the only multivariate predictor of inadequate R100. In terms of inadequate prostate dosimetry, seed strength group was not a predictor for either isotope in multivariate analysis and was a predictor for 125I alone in univariate analysis.

Table 5. Linear regression predictors of R100 inadequacy and prostate dosimetry inadequacy, stratified by isotope
ParameterR100 inadequateProstate dosimetry inadequate
UnivariateMultivariateUnivariateMultivariate
125I
Seed strength group<0.0010.002<0.0010.022
Brachytherapist case volume<0.0010.0010.0050.017
Prostate dosimetry inadequate<0.001
Monotherapy vs. boost therapy<0.001 <0.0010.021
Prescription dose0.770 0.315
Prostate volume0.0230.0010.148
Total adjusted activity0.026 <0.001<0.001
D90%0.0070.001<0.001a
V100%0.393 <0.001a
V150%0.326 <0.001a
V200%0.023<0.001<0.001a

103Pd
Seed strength group0.025<0.0010.4240.015
Brachytherapist case volume<0.0010.0150.0280.011
Prostate dosimetry inadequate<0.001
Monotherapy vs. boost therapy<0.001 <0.001
Prescription dose0.670 0.333
Prostate volume0.036 0.021
Total adjusted activity0.698 <0.0010.002
D90%0.067 <0.001a
V100%0.835 <0.001a
V150%0.205 <0.001a
V200%0.556 <0.001a

aDosimetric parameters were excluded as multivariate analysis predictors for prostate dosimetry inadequate because those parameters define inadequacy.

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Discussion 

Serious brachytherapy-related rectal morbidity has declined over time, reflecting improvements in implantation techniques, identification of postimplant dose thresholds for normal tissue tolerance, and improved ultrasound imaging [5], [6]. The importance of minimizing rectal dose has been demonstrated in multiple prior studies [7], [13], [14], [17]. Unfortunately, serious rectal morbidity, primarily prostatorectal fistulas, occur occasionally (1).

Although there are theoretical studies concluding that higher activity seeds may increase the dose to normal surrounding structures [9], [10], two clinical studies (a small, prospective randomized trial with 40 patients at the University of Michigan (8)) and the current population based Pro-Qura study, both of which demonstrate a lack of correlation between seed activity and rectal dose and at least equivalent prostate dosimetric coverage without higher activity seeds. In the University of Michigan prospective trial of seed strengths, the 125I seed activities intentionally differed by a factor of two (0.60 vs. 0.31mCi/seed), which is much greater than that would be possible in any retrospective analysis, such as this present study. Despite Pro-Qura feedback, inadequate rectal dosimetry was found in a substantial minority of patients and was approximately twice as likely to occur in the 125I cohort (21.1% for 125I and 11.9% for 103Pd). This discrepancy is most likely a result of differences in isotope energy, with the lower average energy of photons from 103Pd causing a more rapid falloff of dose.

In a prior evaluation of the Pro-Qura database, we demonstrated improvements in R100 with brachytherapy experience (12). In this study, there was a correlation between brachytherapist experience and seed activity when stratified by isotope, with HVBs using significantly higher 125I seed activity and significantly lower 103Pd activity. Brachytherapists with high-case volume had lower mean R100 and higher D90, V100, and V150. We found no correlation between seed activity and brachytherapist case volume. However, there was a significantly greater likelihood of R100 inadequacy in the higher activity tertiles of 103Pd implants and the highest likelihood of R100 inadequacy in the intermediate activity tertile of 125I implants. Use of seed activities from the lowest tertile resulted in the lowest specific activity, and, for 125I, this translated into mean V100 and D90 values lower than those of implants from the highest tertile but with no advantage in R100. Paradoxically, the lowest activity tertile of 103Pd had mean V100 and D90 values higher than those of implants from the highest tertile, and these implants also had the lowest mean R100.

Our labeling of some implants as inadequate in terms of rectal, prostate, or overall dosimetry does not equate with negligence on the part of the brachytherapist for many reasons. Suboptimal dosimetry may result from seed loss or seed migration, and for many patients no supplementary action is required. The participating brachytherapists used Pro-Qura for consistent implant evaluations and a means to quality improvement. The Pro-Qura database contains no information regarding any additional therapy offered by brachytherapists to patients with inadequate dosimetry.

Shortcomings of our study include the relatively small ranges of 125I and 103Pd seed activities, variability of postimplant CT timing, and the absence of access to preplans not created by Pro-Qura. There is also no data on ad hoc intraoperative changes to the plans, but specific activity increased with increasing activity tertile, implying that brachytherapists neither increased nor decreased the number of seeds implanted in response to perceived relative seed activity. Strengths of this study include a large sample of 2300 patients from 78 community-based brachytherapists.

In this study, higher activity seeds resulted in at least equivalent prostate dosimetric coverage without a corresponding increase in rectal dose in 125I implants. Higher activity 103Pd seeds did result in higher rectal dose, but 103Pd implants had lower rectal dose than 125I implants. As such, higher activity seeds should result in at least as favorable long-term biochemical control rates as low activity seeds [20], [21]. In the absence of an increased risk of rectal complications, higher seeds will result in a lower implant cost because of the need for fewer seeds.

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Conclusion 

Within the confines of seed activities used in this study, higher activity seeds did not result in a deleterious effect on rectal dose. Higher activity seeds were associated with improved prostate dosimetry for 125I, whereas 103Pd dosimetry was not dependent on seed activity. Postimplant adequacy was more related to prostate coverage than rectal dose for 103Pd, whereas the converse was true for 125I.

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References 

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 Conflicts of interest: John Sylvester and Peter Grimm are owners of Pro-Qura. Jonathan Khanjian is employed by Pro-Qura. No other conflicts of interest exist.

PII: S1538-4721(09)00367-5

doi:10.1016/j.brachy.2009.12.001

Brachytherapy
Volume 10, Issue 1 , Pages 35-43, January 2011

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