A detailed examination of the difference between planned and treated margins in 125I permanent prostate brachytherapy

Results The mean postimplant margin at the base (4±2 mm) was significantly less ( p <0.01) than planned (6±2 mm) by 2 mm. The planned and postimplant margins at the midgland (5±1 mm and 5±2 mm) and apex (7±2 mm and 7±3 mm) were indistinguishable ( p = 0.31 and p = 0.69, respectively). At the base, 69% of the measurements were ⩾3 mm compared with 89% and 91% at the midgland and apex, respectively. Overall, 83% of the margin measurements were ⩾3 mm. The prostate postimplant V 100 and D 90 were 96±4% and 193±27 Gy, respectively. Conclusions A 5-mm planning dose margin can potentially treat most EPE. However, the postimplant margin, like other dosimetric parameters, is sensitive to source placement errors and the percentage of EPE treated depends upon how well the plan is executed. Because implant quality is operator dependent, we would not recommend brachytherapy alone for patients with a high risk of EPE. Keywords Prostate brachytherapy Prostate adenocarcinoma Extraprostatic extension 125 I Introduction Permanent 125I prostate seed implants are typically preplanned to deliver 145 Gy to the prostate plus a 3–5-mm treatment margin. The margin serves a twofold purpose. One is to treat possible extra-capsular extension (EPE) of prostatic cancer. There is growing evidence that EPE may exist in a significant fraction of the favorable risk clinical stage T1-T2 patients (1, 2) . Such EPE has been reported in 10–50% of the patients with clinically organ-confined disease. A second purpose is to provide compensation for source placement errors that might otherwise reduce the prostate dose coverage (3, 4) . It is anticipated that source placement errors will reduce the width of the planned dose margin. The purpose of this study is to determine whether the residual margin is sufficient to treat potential EPE. This study does not attempt to determine whether biochemical failure is a result of lack of extraprostatic treatment, what dose is necessary to treat EPE, or the percentage of the EPE that needs to receive the prescribed dose. Insight regarding the margin width that would be necessary to encompass potential EPE is provided by two studies that quantified the extent of EPE in surgical specimens. Davis et al . (5, 6) reported that 11 of 107 patients who met their criteria for brachytherapy (PSA<10 ng/mL; Gleason<7; volume<60 cc) had EPE, with mean and maximum EPE of 0.03 and 0.6 mm, respectively. Sohayda et al . (7) reported EPE was within 3.3 mm of the capsule in 90% of favorable cases (clinical stage T1-T2; PSA⩽10 ng/mL; Gleason⩽6). These studies indicate that it is not necessary to treat beyond 3 mm from the prostate to cover the vast majority of EPE. Thus, we sought to determine the percentage of the posterior margin that was ⩾3 mm. Methods and materials The postimplant dosimetry of 60 patients who received monotherapy (145 Gy) 125 I prostate implants was evaluated to determine whether the margins adequately covered potential EPE. The mean preimplant prostate volume was 42±10 cm 3 . The implants were planned based on a preimplant CT scan instead of an ultrasound volume study. A peripheral loading approach was used in which the margins were generated primarily by intraprostatic seeding. Figure 1 illustrates a typical plan. At midgland, the seeds were placed around the inside periphery of the prostate. No seeds were implanted in the central region of the prostate at midgland; however, seeds were implanted centrally at the base and apex. Some of the needles that were peripheral at midgland were also used to implant seeds at the base and apex. Because of the reduced dimensions of the prostate at the base and apex, these seeds were often extraprostatic by default ( Fig. 1 ). The implants were planned with a nominal 5-mm dose margin. The margin was not established in a formal manner by drawing a planning target volume (PTV) around the prostate or the gross target volume (GTV). Instead, seed strength and seed locations were selected such that the 145-Gy isodose line was nominally 5 mm outside of the capsule ( Fig. 1 ). The planned implants were performed under ultrasound and template guidance. A postimplant CT scan was obtained 33 days±10 days (range 17–69 days) following the procedure. The scan was performed using a 2-mm slice thickness and 2.5-mm spacing. A single individual (F.M.W.) contoured the prostate on each pre- and postimplant image. To reduce the uncertainty in the postimplant contours, two adjacent workstations were employed to simultaneously view corresponding pre- and postimplant images of the same patient. This allowed for the use of the same visual cues in contouring the pre- and postimplant images. The widths of the preplan and postimplant dose margins were measured at the five positions shown in Fig. 1 . These locations were designated as the left lateral, left posterolateral, posterior, right posterolateral, and right lateral points. We focused on these locations because previous reports have demonstrated EPE to be most prevalent in the posterior regions of the prostate (1, 8–10) . For example, Davis et al . reported that 56% of the EPE sites were in posterior locations, 28% in lateral locations, and only 15% in anterior locations. The margin was measured on 6 images of the prostate in both the preplan and postimplant CT scan of each patient. The goal was to sample the margin at the base, midgland, and apex. Therefore, the margin was measured on the two most superior images (base), the two most central images (midgland), and the two most inferior images (apex). Altogether, the margin was measured at 5 locations on 6 images per patient providing a total of 30 measurements. Results The mean postimplant V 100 and D 90 for the patients in this study were 96±4% and 193±27 Gy, respectively. Thus, the prostate was well covered by the prescribed dose in most cases. The relatively high D 90 is a consequence of generating the 5-mm margin without using extraprostatic seeding, but it is also a reflection of the high V 100 . Table 1 provides a quantitative assessment of the difference in the planned and observed dose margins at the base, midgland, and apex of the gland. The mean planned margins ranged from 4–6 mm except the lateral apex points where the margin was greater (9 mm) because of the presence of extraprostatic seeds ( Fig. 1 ). The minimum margin was found at the posterior point in all three sections of the gland. This reflects our attempt to minimize dose to the rectal mucosa by limiting the posterior margin to 3–5 mm. The overall mean planned margins at the base, midgland, and apex were 6±2 mm, 5±1 mm, and 7±2 mm, respectively. Table 1 also lists the mean postimplant margins, which can be compared with the planned margins. The overall mean postimplant margins at the base, midgland, and apex were 4±2 mm, 5±2 mm, and 7±3 mm, respectively. The mean postimplant margin at the base was significantly ( p <0.01) less than planned by 2 mm. However, the mean preplan and postimplant margins at the mid-gland and apex are indistinguishable ( p = 0.31 and p = 0.69, respectively). This indicates that, in general, the planned margins were not significantly reduced by deviations in source placement in these regions. However, this was not true at the base. Figures 2a–c show the frequency distribution of the planned and postimplant margins measured at the base, mid-gland, and apex of the prostate. The vertical dashed line is a reference line that delineates a 3-mm margin, the assumed minimum requirement for adequate coverage of EPE. These plots provide insight into how reliably the planned and postimplant margins encompassed the potential EPE. Note that the planned margins, denoted by open squares and a dashed line, were sometimes less than the 3 mm deemed necessary to treat EPE. The portion of the plotted curves to the left of the vertical dashed line indicates this. Specifically, 10%, 6%, and 5% of the planned margins at the base, midgland, and apex were <3 mm. This is not surprising because a 3-mm minimum constraint was not placed on the margin in planning the implants. Closed circles and the solid line denote the postimplant margins. At the base ( Fig. 2a ), the distribution of the margin measurements is shifted to the left, toward smaller margins. Note also that a significant number of these measurements were negative. A measurement of −3 mm, for example, means that the 145-Gy isodose line was within the prostate 3 mm from the edge of the gland. Sixty-nine percent of the measured margins at the base were ⩾3 mm. This indicates that, in general, the plans were not as well executed at the base as at the midgland and apex, where there is little difference between distributions of planned and postimplant margin measurements. At the midgland and apex, 89% and 91% of the postimplant margin measurements, respectively, were ⩾3 mm, which is approximately the same as planned. Overall, 93% of the planned margins and 83% of postimplant margins, respectively, were ⩾3 mm at the points measured. Table 2 is a detailed analysis of the number of margin measurements per patient that were <3 mm. A total of 30 measurements were made per patient. The number of these that were <3 mm is listed in the first column and the number of patients for which this was true is listed in the second column. Thus, 6 patients had no measurements <3 mm, 7 had 1 measurement <3 mm, 5 had 2 of measurements <3 mm, etc. The margin was <3 mm at one or more locations in most (90%) patients. The median number of measurements that were <3 mm was 4 per patient. At the other extreme, the 11 patients in the right-hand column of Table 2 had 10–18 measurements <3 mm. The results in Table 2 indicate that there was a wide variation in the dose coverage of EPE in the patient population and that it ranged from ∼40% to 100% with a mean coverage of 83%. Discussion The patients in this study were planned with generous dose margins that had a mean value of 5±1 mm at midgland. The mean postimplant margins were indistinguishable from the mean planned margins at the midgland and apex and adequate to treat EPE at ∼90% of the points sampled. However, at the base, the mean postimplant margins were typically 2 mm less than planned. Nevertheless, the residual margin at the base was still adequate to treat potential EPE at 69% of the points sampled. These results generally agree with our earlier study based on 103 Pd implants (11) . There are limitations in the present study with respect to the experimental uncertainty in determining the margin width. This is the uncertainty in contouring the prostate from which the distance of the 145-Gy isodose line was measured. The uncertainty is due both to the voxel size of the CT scan and the uncertainty in distinguishing the prostate capsule from surrounding soft tissues, most notably at the apex. The uncertainty in the localization of the contour is estimated to be 1–2 mm depending upon the portion of the prostate being contoured. Thus, an individual margin measurement may either too large or too small by 1–2 mm. Because this uncertainty is random in nature, the overall impact on this study is believed to be negligible. Furthermore, the same individual performed all of the contouring on pre- and postimplant CT images of equal quality so that interobserver variability was not an issue. It is interesting to note that many implants that are considered adequate because D 90 ⩾140 Gy would not provide complete coverage of EPE. When D 90 = 140 Gy, V 100 is by definition <90%. Whenever V 100 is <100%, some portion of the prostate volume is not encompassed by the 145-Gy isodose surface and there generally would be no margin over this portion of the prostate for treatment of EPE. Thus, a minimum requirement for complete coverage of EPE is that V 100 = 100%. In addition, the margin would have to be ⩾3 mm over the entire prostate volume. It is not the purpose of this study to determine whether all of the potential EPE must be treated to 145 Gy. However, if this is so, it appears that it would be necessary to raise the minimum standards of prostate dosimetry. It is unlikely that a 5-mm planning margin generated without extraprostatic seeding will suffice to provide consistent treatment of all potential EPE unless the precision of source placement is improved. Alternatively, it may be necessary to utilize extraprostatic seeding to provide consistent treatment of all potential EPE. Because implant quality is operator dependent, we would not recommend brachytherapy alone in the treatment of patients at high risk for EPE at this time. Some physicians may choose to treat this potential clinical problem with extraprostatic seeds, supplemental external beam radiation therapy, both or to forgo an implant altogether. The role and importance for supplemental external beam radiation is unclear with the only published report on a randomized trial limited to toxicity data thus far (12) . There are no useful guidelines or prospective data to help with this decision making process. The Radiation Therapy Oncology Group clinical trial, RTOG 0232, will address this question by randomizing intermediate risk patients to either external beam with an implant boost or implant alone. Conclusion A 5-mm planning dose margin can potentially treat most EPE. However, the postimplant margin, like other dosimetric parameters, is sensitive to source placement errors and the percentage of EPE treated depends upon how well the plan is executed. In this study, 69%, 89%, and 91% of the postimplant margin measurements at the base, midgland, and apex of the gland, respectively, were sufficient (⩾3 mm) to treat EPE. Because implant quality is operator dependent, we would not recommend brachytherapy alone for patients with a high risk of EPE. References [1] J.I Epstein A.W Partin J Sauvageot Prediction of progression following radical prostatectomy. 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