A comparison of permanent prostate brachytherapy techniques: preplan vs. hybrid interactive planning with postimplant analysis

PURPOSE: To compare preparation time, procedure time in the operating room, equipment needs, and Day 0 postimplant dosimetry between two different Mick implant techniques performed at a single institution. METHODS AND MATERIALS: One hundred consecutive monotherapy patients treated from 1999 to 2000 with 125I transperineal permanent implantation of the prostate using an afterloading Mick applicator were evaluated. The first 40 patients were treated with a preplanned modified peripheral loading Mick technique. The next 60 were treated with a hybrid interactive image-guided Mick technique. The analysis included planning the following: ultrasound volume, time required of preplanning, Day 0 CT volume, number of seeds, number of needles, activity per seed, total activity of the implant, and procedure time. Dosimetric parameters included D(90), V(100), and V(150). RESULTS: Mean planning ultrasound volume (33 vs. 37 cc), Day 0 CT volume (49 vs. 47 cc), mCi/seed (0.30 vs. 0.34 mCi/seed), number of seeds (121 vs. 96), total activity of the implant (36 vs. 32 mCi), D(90) (132 vs. 149 Gy), V(100) (86% vs. 91%), and V(150) (51% vs. 38%) were comparable. Significant differences (p < 0.01) were noted in mean preplan time (30 vs. 7 min), number of needles (32 vs. 19), and procedure time (90 vs. 40 min). CONCLUSIONS: Hybrid interactive Mick prostate brachytherapy consistently reduces preplanning time, procedure time, and number of needles used, reducing patient treatment time and costs while maintaining excellent dosimetric coverage. Use of hybrid interactive Mick prostate brachytherapy results in improved therapeutic ratios, i.e., maintains Day 0 D(90) >140 Gy, V(100) >90%, and V(150) <40%, without the need for sophisticated three-dimensional intraoperative planning technology.     

Is intraoperative nomogram-based overplanning of prostate implants necessary?

PURPOSE: Several investigators have described intraoperative planning of prostate implants based on a nomogram. The aim of this work was to investigate the adequacy of the nomogram in predicting the total activity necessary for optimal dosimetry. METHODS AND MATERIALS: Eighty CT-based postimplant treatment plans were performed for patients who underwent ultrasound guided I-125 permanent implants alone between April 2000 and March 2001. The cohort of 40 patients had early stage (T1-T2) prostatic carcinoma and pre-treatment prostate volumes of 19-50 cc. I-125 seeds (0.391 mCi/seed) were implanted to achieve a distribution of 75% of the activity peripherally and 25% centrally. The CT studies were obtained on the day of (CT1) and at 1 month (CT2) after implant. All patients were catheterized at CT1, and 28 patients were catheterized at CT2 to visualize the urethra. For each patient, the percentage difference (dA) between the total implanted and nomogram predicted activity for a known prostate volume was calculated. The V200 (volume receiving 200% of the prescribed dose), V150, V100, V90, D100 (maximum dose received by 100% of the volume), D90, and D80 were measured for the prostate at CT1 and CT2. For the urethra, V275, V250, V200, and V150 were evaluated, and V100 and V70 were evaluated for the rectum. The Pearson test was used to correlate the dosimetric parameters with dA. Linear regression was used to fit the correlation of the volume and dose parameters with dA. RESULTS: The median V100 at CT1 and CT2 was 91.8% and 94.2%, respectively. The Pearson test was significant for the prostate V100 and dA measured at CT1 (p = 0.005) but not at CT2 (p = 0.106). A similar correlation was found for the prostate D90 at CT1 (p = 0.002), but not at CT2 (p = 0.076). D100 (maximum dose received by 100% of volume) for prostate did not correlate with dA at CT1 (p = 0.094) and CT2 (p = 0.148). The volume of the prostate receiving higher doses (greater than 150% and 200% of the prescribed dose) correlated with dA. There were no significant correlations between V275, V250, V200, and V150 at CT1 and CT2 as a function of dA for the urethra. V100 and V70 for the rectum correlated significantly with dA; for V100, p = 0.041 at CT1 and p = 0.014 at CT2 and for V70, p = 0.041 at CT1 and p = 0.026 at CT2. A linear regression model fitted to the prostate data obtained from CT1 with the goal of achieving a V100 of 90% and D90 of 145 Gy suggests that no increase in the number of seeds may be warranted using intraoperative planning. The implants examined showed no concomitant increase of urethral doses with increase in activity relative to the nomogram, but showed an increase in the rectal doses for the same increase in activity. CONCLUSION: The doses evaluated at CT1 represent an underestimate, whereas those obtained at CT2 represent an overestimate of the actual delivered protracted permanent implant dose. Based on these results and consideration of the dynamic nature of the dose distribution, target coverage obtained with intraoperative planning using the nomogram predicted activity is consistent with published guidelines for a quality implant and critical structure doses are within tolerance.     

Influence of prostate volume on dosimetry results in real-time 125I seed implantation

PURPOSE: Achieving a minimal dose of 140 Gy to 90% of the prostate (D90) on postimplant dosimetry has been shown to yield improved biochemical control by 125I brachytherapy, and a D90 >180 Gy can be associated with increased long-term toxicity of seed implantation. Significant enlargement of the prostate on postimplant CT compared with the ultrasound (US) volume at implantation (CT/US ratio) has been associated with lower dose results, but other factors predicting for high or low doses are not well established. We determined whether the prostate size at implantation influenced the CT/US ratio results affecting postimplant dosimetry or predicted for D90 values <140 or >180 Gy in patients implanted with 125I in a community hospital setting. METHODS AND MATERIALS: The dosimetry results from 501 patients from 33 community hospitals were analyzed after full dose 125I implantation. Implant radioactivity was obtained from reference tables relating millicuries to prostate volume (PV). Seeds were placed under real-time US guidance with peripheral weighting in a uniform method for all prostate sizes. CT-based dosimetry was performed 1 month after implantation. Dose-volume histogram parameters were analyzed for volume effects, including D90, the dose to 10% and 30% of the rectal wall, and the dose to 30% of the urethra and bladder. The PV was defined as small (<25 cm3), medium (25 to <40 cm3), or large (> or =40 cm3). RESULTS: The PV ranged from 9 to 79 cm3 (median 32.7). A D90 > or =140 Gy was achieved in 452 patients (90%). The median D90 was 164 Gy (range 90-230) and increased from 149.5 Gy in small prostates to 164 Gy in medium (p <0.001) and 176 Gy in large (p <0.001) prostates. A D90 <140 Gy occurred in 20% of small vs. 9% of medium and 3% of large prostates (p = 0.003). A D90 >180 Gy occurred in 7% of small and 10% of medium vs. 25% of large glands (p <0.001). The rectal dose increased significantly with an enlarging PV. The bladder and urethral doses increased from the small to medium PVs, although did not increase further in the large glands. The median CT/US ratios showed a significant volume relationship, decreasing with enlarging PVs, but were not associated with a D90 <140 or >140 Gy. The D90 results for <140 Gy and >140 Gy occurred at equal activities per volume. CONCLUSION: Ninety percent of patients implanted by community-level practitioners using reference tables and real-time US-guided implantation achieved a D90 outcome of > or =140 Gy. Significant differences in dose outcomes <140 Gy and >180 Gy occurred related to PV. Those with prostates <25 cm3 had a 20% frequency of D90 <140 Gy, unrelated to excessive postimplant volume enlargement or insufficient activity per reference table, suggesting that the activity-to-volume recommendations may not allow for much variance in final seed position. Such seed displacement may contribute to lower doses, most commonly in small glands. One may consider increasing the activity implanted in small prostates, because a D90 >180 Gy occurred in only 7% of these cases. Patients with glands >40 cm3 were 25% likely to have a D90 result >180 Gy and were at only 3% risk of a D90 <140 Gy. These patients may benefit from intraoperative dosimetry or a reduction in implant activity.     

Prostate brachytherapy post-implant dosimetry: a comparison between higher and lower source density.

BACKGROUND AND PURPOSE: To compare post-implant dosimetry between high density source implants (HDI) and low density source implants (LDI). MATERIALS AND METHOD: Dosimetric analysis of the whole prostate (V200, V150, V100, D90, D80, contiguous V200 and V150, external index), prostate quadrants (V200, V150, V100, D90), rectum (V150, V120, V100, V80, V60) and deviated surrogate urethra (V200, V150, V120, V100, V80) was performed on 39 consecutive prostate brachytherapy LDI and 39 volume matched HDI over the same time period. The distinction between LDI and HDI was based on differing prescribed dose using 125-Iodine sources, with MPD of 115 and 144 Gy, respectively, using a fixed source strength of 0.424 U (0.334 mCi). Cases were contoured by two independent blinded observers. Repeated measures analysis of variance was used to look at the effects of treatment arm, observer and their interaction. RESULTS: Whole prostate (WP) volume did not differ significantly between the treatment arms, mean of 25.4 cc for LDI and 26.6 cc for HDI. There was no significant difference in any of the measured post-implant dosimetric parameters for the WP or quadrants, surrogate urethra or rectum. CONCLUSIONS: No difference in post-implant dosimetric parameters was observed between Iodine 125 LDI and HDI. Neither dose homogeneity nor conformality is compromised with a lower source density. Higher strength sources have the potential for considerable cost saving and reduced morbidity.     

Rectal-wall dose dependence on postplan timing after permanent-seed prostate brachytherapy

PURPOSE: Dose to rectal wall after permanent-seed prostate brachytherapy is dependent on distance between posterior prostatic seeds and anterior rectal wall and is influenced by postimplant periprostatic edema. We analyzed the effect of postplan timing on anterior rectal-wall dose. METHODS AND MATERIALS: Twenty patients received permanent seed 125I brachytherapy as monotherapy (145 Gy). Implants were preplanned by use of transrectal ultrasound (TRUS) and carried out by use of preloaded needles. Postimplant dosimetry was calculated by use of magnetic resonance imaging-computed tomography fusion on Days 1, 8, and 30. The anterior rectal-wall dose is reported as the isodose enclosing 1.0 or 2.0 cc of rectal wall and as the RV100 in cc. RESULTS: The dose to rectal wall increased progressively over time. The median increase in dose to 1.0 cc of rectal wall (RD [1 cc]) from Day 1 to 30 was 39.2 Gy (p < 0.001). RV100 increased from a median of 0.07 cc on Day 1 to 0.67 cc on Day 30. The most significant predictor of rectal-wall dose (RD [1 cc], RD [2 cc], or RV100) was the time of evaluation (p < 0.001). CONCLUSION: Although periprostatic edema cannot be quantified by postimplant imaging, the dose to the anterior rectal wall increases significantly over time as prostatic and periprostatic edema resolve. Critical-organ dose reporting and guidelines for minimizing toxicity must take into account the time of the assessment.     

Prostate brachytherapy in patients with prostate volumes ≥ 50 cm: dosimetic analysis of implant quality

Objectives: Permanent implantation with ¹²⁵I in patients with localized prostate cancer who have prostate volumes ≥ 50 cm³ is often technically difficult owing to pubic arch interference. The objective of this study was to describe dosimetry outcomes in a group of patients who were implanted using the real-time ultrasound-guided technique who had prostate volumes ≥ 50 cm³.

Materials and Methods: A total of 331 patients received an ¹²⁵I prostate seed implant from January 1, 1995, to June 1, 1999, of whom 66 (20%) had prostate volumes ≥ 50 cm³ at the time of the procedure. The real-time seed implant method was used in all patients and consisted of intraoperative planning and real-time seed placement using a combination of axial and sagittal ultrasound imaging. Pubic arch interference was managed using an extended lithotomy position or by angling the tip of the ultrasound probe in an anterior direction. No preimplant pubic arch CT scan study was performed and no patients were excluded from treatment because of prostate size. Implant quality was assessed using CT-based dosimetry performed 1 month postimplant. Dose–volume histograms for the prostate, bladder, rectum, and urethra volumes were generated. The target dose for these implants was 160 Gy and an adequate implant was defined as the dose delivered to 90% of the prostate (D90) ≥ 140 Gy. The dose delivered to 95% of the prostate (D95) and doses to 30% of the rectal (DRECT30) and urethral (DURE30) volumes were also calculated.

Results: Prostate volumes in the 66 patients ranged from 50 to 93 cm³ (median 57, mean 61 cm³). Total activity implanted was 27.8–89.1 mCi (median 57 mCi), with a range in activity per seed of 0.36–0.56 mCi (median 0.4 mCi). The prostate D90s and D95s ranged from 13,245 to 22,637 cGy (median 18,750) and 11,856 to 20,853 cGy (median 16,725), respectively. Only one patient (1.5%) had a D90 < 140 Gy. The DURE30 values ranged from 15,014 to 27,800 cGy (median 20,410) and the DRECT30 values were 3137–9910 cGy (median 5515).

Conclusion: Implantation of the large prostate can be accomplished using the real-time method. A total of 98.5% of the patients receive a high-quality implant. In addition, these implants should not put patients at increased risk for significant urinary and bowel complications because urethral and rectal doses can be kept at acceptable levels.     

MRI-based preplanning in low-dose-rate prostate brachytherapy

PURPOSE: To compare the dosimetric results between MRI-based and TRUS-based preplanning in permanent prostate brachytherapy, and to estimate the accuracy of MRI-based preplanning by comparing with CT/MRI fusion-based postimplant dosimetry. METHODS AND MATERIALS: Twenty-one patients were entered in this prospective study with written informed consent. MRI-based and TRUS-based preplanning were performed. The seed and needle locations were identical according to MRI-based and TRUS-based preplanning. MRI-based and TRUS-based preplanning were compared using DVH-related parameters. Following brachytherapy, the accuracy of the MRI-based preplanning was evaluated by comparing it with CT/MRI fusion-based postimplant dosimetry. RESULTS: Mean MRI-based prostate volume was slightly underestimated (0.73 cc in mean volume) in comparison to TRUS-based volume. There were no significant differences in the mean DVH-related parameters except with rectal V(100)(cc) between TRUS-based and MRI-based preplanning. Mean rectal V(100)(cc) was 0.74 cc in TRUS-based and 0.29 cc in MRI-based preplanning, respectively, and the values demonstrated a statistical difference. There was no statistical difference in mean rectal V(150)(cc), and rectal V(100)(cc) between MRI-based preplanning and CT/MRI fusion-based postimplant dosimetry. CONCLUSION: Prostate volume estimation and DVH-related parameters in MRI-based preplanning were almost identical to TRUS-based preplanning. From the results of CT/MRI fusion-based postimplant dosimetry, MRI-based preplanning was therefore found to be a reliable and useful modality, as well as being helpful for TRUS-based preplanning. MRI-based preplanning can more accurately predict postimplant rectal dose than TRUS-based preplanning.     

Significant correlation between rectal DVH and late bleeding in patients treated after radical prostatectomy with conformal or conventional radiotherapy (66.6-70.2 Gy)

PURPOSE: Investigating the correlation between dosimetric/clinical parameters and late rectal bleeding in patients treated with adjuvant or salvage radiotherapy after radical prostatectomy. METHODS AND MATERIALS: Data of 154 consecutive patients, including three-dimensional treatment planning and dose-volume histograms (DVHs) of the rectum (including filling), were retrospectively analyzed. Twenty-six of 154 patients presenting a (full) rectal volume >100 cc were excluded from the analysis. All patients considered for the analysis (n = 128) were treated at a nominal dose equal to 66.6-70.2 Gy (ICRU dose 68-72.5 Gy; median 70 Gy) with conformal (n = 76) or conventional (n = 52) four-field technique (1.8 Gy/fr). Clinical parameters such as diabetes mellitus, acute rectal bleeding, hypertension, age, and hormonal therapy were considered. Late rectal bleeding was scored using a modified Radiation Therapy Oncology Group scale, and patients experiencing >or=Grade 2 were considered bleeders. Median follow-up was 36 months (range 12-72). Mean and median rectal dose were considered, together with rectal volume and the % fraction of rectum receiving more than 50, 55, 60, and 65 Gy (V50, V55, V60, V65, respectively). Median and quartile values of all parameters were taken as cutoff for statistical analysis. Univariate (log-rank) and multivariate (Cox hazard model) analyses were performed. RESULTS: Fourteen of 128 patients experienced >or=Grade 2 late bleeding (3-year actuarial incidence 10.5%). A significant correlation between a number of cutoff values and late rectal bleeding was found. In particular, a mean dose >or=54 Gy, V50 >or=63%, V55 >or=57%, and V60 >or=50% was highly predictive of late bleeding (p or=63% and those with V50 <63% (DVH grouping), data were fitted with a Cox regression hazard model using DVH grouping, rectal volume, and the main clinical parameters as independent variables. Results of the analysis showed that DVH grouping (relative risk 3.3; p = 0.04) and acute bleeding (relative risk 7.1; p = 0.001) are independently predictive of late bleeding. CONCLUSIONS: DVHs of the rectum are significantly correlated with late bleeding for patients irradiated at 66.6-70.2 Gy after radical prostatectomy.     

The robustness of dose distributions to displacement and migration of 125I permanent seed implants over a wide range of seed number, activity, and designs

PURPOSE: To investigate the robustness of permanent prostate implant dosimetry for various (125)I seed activities and various seed models. The dosimetric impact of seed misplacement and seed migration (seed loss) is also taken into account using various standard dose indices. METHODS AND MATERIALS: A dose-based inverse planning algorithm is used for automated dosimetric plan creation (45-60 s per plan) and provides an unbiased way to compare the robustness of various optimal dosimetric plans. Seed misplacement and seed migration are simulated by way of Monte Carlo, based on the measured displacement distributions from clinical postimplant cases. Plans were generated for seed activities between 0.2 and 1.4 mCi (0.25 to 1.78 U) and for 11 different seed models. RESULTS: The numbers of seeds and needles are shown to decrease rapidly for a seed activity between 0.3 mCi and 0.6 mCi (0.38 and 0.76 U). The loss in V100, from 100%, because of seed misplacement is below 10% for an apparent activity ranging from 0.2 to 0.9 mCi (0.25 to 1.14 U). A minimum degradation in V100 is observed around 0.6-0.7 mCi (0.76-0.89 U). D90 increases from 150 to 170 Gy between 0.3 and 0.7 mCi (0.38 and 0.89 U) and decreases afterward to fall below 140 Gy at higher activity. V200 and D10 to the target volume both show an increase in hot spots up to 0.7 mCi, and then decrease linearly at higher activities for all seed models. V200 and D10 to the urethra remain about constant for all seed activities up to 0.8 mCi (1.02 U), at which point they start to decrease. All seed models follow this general trend. CONCLUSIONS: Plans were shown to be robust to misplacement and migration of seeds over a wide range of seed activity and for various seed models. With a properly tuned inverse planning algorithm able to ensure the dose coverage and protection for the organs at risk in the presence of placement errors (displacement and migration), the choice of a preferred seed activity, in a range up to about 0.7 mCi (0.89 U), is open. The upper part of this range offers the opportunity to significantly reduce the number of seeds and needles, thus reducing surgical trauma to the patient, saving time in an operating room planning setting, and reducing the cost of a permanent prostate implant procedure.