- Email: [email protected]
Importance of Post-Implant Dosimetry in Permanent Prostate Brachytherapy
European Urology
European Urology 41 (2002) 434±439
Importance of Post-Implant Dosimetry in Permanent Prostate Brachytherapy Richard G. Stocka,*, Nelson N. Stoneb a
Department of Radiation Oncology, Mount Sinai School of Medicine, Box 1236, 1184 5th Avenue, New York, NY 10025, USA Department of Urology, Mount Sinai School of Medicine, New York, NY, USA
b
Accepted 15 June 2001
Abstract Objective: Post-implant dosimetry has become the gold standard for implant evaluation and it is recommended that it be performed on all patients undergoing prostate brachytherapy. The technique, results and correlation with clinical outcomes will be presented. Methods: The method and outcomes of post-implant dosimetry are explored by outlining the experience at the Mount Sinai Medical Center, New York, as well as reviewing the literature. The most accurate time to perform postimplant dosimetry is 1 month after implant. Computed tomography (CT)-based dosimetry is currently the best available technique for performing this analysis. The technique involves taking 3-mm abutting CT slices throughout the implanted area. The prostate and normal structures are outline on the CT slices. These structures are recreated in three dimensions. Dose volume histograms (DVH) are created and allow the dose to these organs to be quanti®ed. Results: The relationship between dosimetric ®ndings and clinical outcomes has been established. The dose delivered to 90% of the prostate on DVH (D90) has been correlated to prostate-speci®c antigen (PCA) control and post-treatment biopsy results. D90 values of 140 Gy have been associated with improved biochemical control and lower positive post-treatment biopsy results. Doses derived from the dosimetric analysis to prostate, urethra and rectum have been correlated with the development of acute and chronic urinary morbidity, sexual potency and rectal morbidity. Future initiatives involve performing dosimetric calculations intraoperatively at the time of the implant. Conclusions: Post-implant CT-based dosimetry is an essential component of prostate brachytherapy. It is the only method of assessing the actual dose delivered to the prostate and normal surrounding structures. Future development in post-implant and intraoperative dosimetry will continue to improve permanent prostate brachytherapy as a safe an effective treatment for prostate cancer. # 2002 Published by Elsevier Science B.V. Keywords: Prostate cancer; Brachytherapy; Dosimetry 1. Introduction The lessons learned from the retropubic era of prostate brachytherapy are that implant quality can greatly affect treatment outcomes. The inadequate technology available at that time resulted in poor seed distribution throughout the prostate gland. This led to higher tumor recurrence rates compared to other therapeutic modalities [1,2]. Unfortunately, at that time there did not exist an adequate method for evaluating *
Corresponding author. Tel.: 1-212-241-7502; Fax: 1-212-410-7194. E-mail address: [email protected] (R.G. Stock).
implant quality. The only technique available at that time involved plain X-rays of the pelvis to determine seed locations. Although this process demonstrated the radiation dose distribution around the seeds, there was no way of relating these doses to the actual prostate since the gland was not imaged. Despite these limitations, the total dose delivered by these retropubicly implanted seeds was correlated to local failure as measured by the digital rectal examination [3]. These data highlighted the need for implant quality evaluation and demonstrated the importance of the delivered dose in achieving tumor control. During the advent of the transperineal ultrasound-guided seed implant technique
0302-2838/02/$ ± see front matter # 2002 Published by Elsevier Science B.V. PII: S 0 3 0 2 - 2 8 3 8 ( 0 2 ) 0 0 0 1 8 - 0
R.G. Stock, N.N. Stone / European Urology 41 (2002) 434±439
a newer more accurate method of implant quality evaluation was developed. This new method, known as computed tomography (CT)-based post-implant dosimetry, utilized CT to image the prostate and allowed the location and dose distribution of the seeds to be directly related to the actual prostate [4,5]. Postimplant dosimetry has become the gold standard for implant evaluation and it is recommended by the American Brachytherapy Society, the American Association of Physicists in Medicine and the ESTRO/EAU/ EORTC that it be performed on all patients undergoing permanent prostate brachytherapy [6±8]. The technique and methods of analyzing post-implant dosimetry developed at the Mount Sinai Medical Center, New York, as well as clinical correlations and a literature review will be presented in order to show its crucial role in the continued improvement of prostate brachytherapy. 2. Materials and methods 2.1. Post-implant dosimetry technique The most commonly used and best technique currently available for performing dosimetry is CT-based [6]. The technique developed at the Mount Sinai School of Medicine, New York, NY, is employed by taking 3-mm abutting CT slices throughout the implanted area [5]. On every CT slice, the prostate is contoured. The urethral location is estimated in the majority of cases by comparison with ultrasound images or by the use of a Foley catheter. The inner and outer wall of the bladder and rectum are outlined. The ADAC (Milpitas, CA, USA) pinnacle system is used to perform the dosimetry calculations. Seed locations are identi®ed on every CT slice. The total number of seeds implanted is cross checked with the number of seeds counted on orthogonal X-ray ®lms. All structures are reconstructed in three dimensions and dose distributions to these structures are calculated.
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2.2. Outlining the prostate volume Multiple methods exist for outlining the prostate on the postimplant CT study. Merrick et al. [9] describe three methods: outlining the prostate plus a periprostatic margin; outlining the prostate only which excludes the puborectalis muscles, the periprostatic fat and the periprostatic venous plexus, and superimposing the pre-planning ultrasound volume magni®ed to conform to the magni®cation factor of the post-implant CT. They found little differrence in the dosimetric ®ndings using the different volume approaches [9]. The Mount Sinai technique utilizes the features of the ADAC pinnacle system to enhance the accuracy of the volume determination. The image is enlarged to exclude all surrounding structures beyond the bladder, prostate, seminal vesicles and rectum. The CT images are set at a window of 400 and a level of 800 to enhance soft tissue delineation. The prostate is outlined without a margin. The periprostatic venous plexus and fat as well as surrounding musculature are excluded (Fig. 1). This technique has resulted in a good correlation between the ultrasound volume and the CT volume. In a study of 297 125I post-implant dosimetry analyses, the CT/ultrasound volume ratios were between 0.8 and 1.2 in 74% of cases [10]. 2.3. Timing of post-implant dosimetry Since implantation can cause swelling and edema within the gland, which can alter the prostate volume, the timing of the implant analysis is important. Prostate volume increases on average have ranged from 20 to 50% [11±15]. The half-life of this edema has been reported to be about 10 days [11]. Although performing dosimetry 1 day after implantation may be the most convenient, the edema on this day has been reported to cause an average increase in prostate volume of 52%. This will result in an approximate 10% decrease in the calculated delivered dose [11]. For this reason, the 1-month time has been used to perform dosimetry. The dose calculated at 1 month has been shown to most accurately represent the delivered dose over the life of the implant [14]. It is felt that the most reproducible results will be obtained by performing dosimetry at this time [6]. 2.4. Dosimetry analysis The information obtained from the post-implant CT scan can be used to generate dose volume histograms (DVH). These plots
Fig. 1. Transverse CT image of implanted prostate: (a) without contoured prostate; (b) with prostate contoured.
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describe the dose distribution of the prostate. Using the DVH, the amount of prostate receiving a given dose of radiation can be obtained. Terms such as D100, D90 and D80 refer to the amount of dose delivered to 100, 90 and 80%, respectively, of the prostate volume as outlined on the CT slices. Conversely terms such as V100, V150 refer to the volume of the prostate receiving 100 and 150%, respectively, of the prescription dose. Since there may be small errors in outlining the prostate as well as small areas within the prostate that are underdosed, the term D90 has been adopted as the best description of delivered dose [6,7]. In addition, the D90 is the only dose parameter that has been correlated to the prostate-speci®c antigen (PSA) response [16]. The D100 is a poor dose description since it is extremely sensitive to the volume drawn as well as any areas, no matter how small, which are underdosed. In addition D100 has been shown to poorly correlate to the D90 [10,17].
3. Results Most available information on post-implant dosimetry comes from studies on 125I prostate seed implantation. There is currently little data available on dosimetry following 103Pd implants. Extrapolations of the data on 125 I dosimetry to 103Pd dosimetry are dif®cult due to the inherent differences in dose rate, half life and tissue attenuation between the two isotopes. There are few reports on post-implant dosimetry results with large numbers of patients. Many analyses have been used to show that the exact pre-planned dose coverage used for a pre-planning technique can rarely be achieved [18±22]. Willins and Wallner [18] showed that on average only 84% (76±92%) of the target was covered by the prescription dose of 140 Gy. These reports emphasize the importance of the post-implant analysis since the pre-plan will rarely represent the actual delivered dose. The largest dosimtery report comes from Stock et al. [10]. In this study, 297 patients implanted using a realtime ultrasound-guided technique with 125I alone (prescription dose 160 Gy) without external beam irradiation underwent 1 month CT-based dosimetry. All prostate volumes were outline by one person. In this study, the median D100, D95, D90 and D80 were 102, 157, 176 and 199 Gy, respectively. In addition, the median V100 and V150 were 94 and 56%, respectively. The study also showed that factors associated with more precise implantation such as decreased postimplant edema, newer technology and increased number of seeds would lead to higher D90 values [10]. 3.1. Clinical correlation 3.1.1. PSA and biopsy data The ®rst clinical correlation of dosimetry results to PSA control was reported by Stock et al. [23]. In this
study, 134 patients with T1±T2 prostate cancer underwent 125I seed implantation alone. Since these patients were treated from 1990 to 1996 and changes in technique and the amount of activity implanted per volume were made over this time, different prostatic doses were delivered. Based on these doses, a dose-response analysis was performed. The study revealed that those patients receiving D90 values of 140 Gy had an improved biochemical control rate (PSA 1.0 ng/ ml) of 92% at 4 years compared to 68% for those patients with D90 values of <140 Gy ( p 0:02) [13]. An update of these data continues to support a close relationship between delivered dose (D90) and tumor control. In 180 patients, freedom from PSA failure (FFPF) at 6 years was 60% for D90 <140 Gy, 97% for 140±160 Gy, 98% for 160±180 Gy, and 95% for >180 Gy (p 0:0025). Overall, patients with doses of <140 Gy (median follow-up 66 months) had a FFPF of 60% compared to 96% for patients with doses of 140 Gy (median follow-up 35 months; p 0:0002) [23]. In addition, this type of dose response was demonstrated with respect to 2-year post-treatment prostate biopsies. In 113 patients, positive biopsies were found in 23% for doses of <140 Gy, 21% for 140±160 Gy, 10% for 160±180 Gy, and 8% for 180 Gy. Overall, biopsies were positive in 22% for doses of <160 Gy versus 9% for 160 Gy ( p 0:05) [23]. 3.2. Acute urinary morbidity Acute urinary symptoms such as frequency, dysuria, urgency, nocturia and weak stream are common side effects of prostate brachytherapy. These symptoms usually occur 1±2 weeks after implantation and can last for months following the procedure. Most acute urinary symptoms subside by 1 year following brachytherapy [24±27]. In a study by Desai et al. [24], acute urinary symptoms as assessed by the international prostate symptom score (IPSS) were correlated to dosimetric parameters in 117 patients treated with 125 I prostate seed implantation. This study found that increasing doses delivered to the prostate resulted in increased urinary symptoms. The D90 correlated well with the total IPSS ( p < 0:001). In addition, the dose delivered to 5 cm2 of urethra correlated with the maximal frequency score ( p 0:04) [24]. Others have not found DVH parameters to affect acute morbidity [26,27]. 3.3. Chronic urinary morbidity Fibrosis and necrosis that can occur within the prostate and urethra secondary to irradiation can cause chronic urinary morbidity. Typically, these late
R.G. Stock, N.N. Stone / European Urology 41 (2002) 434±439
radiation changes develop 18 months or longer following implantation. The ®rst study to examine the relationship between urinary morbidity and dosimetric parameters was by Wallner et al. [28]. In this study, the dose delivered to the urethra in 45 patients treated with 125I seed implantation was correlated to the radiation therapy and oncology group (RTOG) morbidity scale. This study found an association with the length of urethra receiving 400 Gy and the RTOG morbidity score. Patients with RTOG grades 0±1 urinary morbidity had an average of 1 cm of urethra irradiated to >400 Gy compared to 2 cm for patients with grade 2±3 morbidity (p 0:07) [28]. In a larger study by Stock et al. [23], the relationship between prostate dose and late urinary morbidity was assessed in 276 patients treated with 125I seed implantation and followed from 18 to 108 (median 34) months. The relationship between prostate D90 and the last IPSS was examined by comparing the patients' pre-treatment IPSS to their last follow-up IPSS in different D90 dose groups. There were minimal changes in IPSS seen in the dose groups <140, 140±160, and 160±180 Gy. For patients receiving D90 of >180 Gy, there was signi®cant worsening of the mean scores from 0.5 to 1.0 ( p 0:002) for emptying, 0.76 to 1.29 ( p 0:004) for weak stream, 0.24±0.51 ( p 0:009) for straining, 1.55 to 1.82 ( p 0:05) for nocturia, and 6.3±8.45 ( p 0:0009) for total score [23]. These data suggest that a higher prostatic dose of >180 Gy may lead to increased late urinary symptoms. 3.4. Sexual potency Theoretically, the dose delivered to the prostate could have a signi®cant impact on erectile function preservation, since the neurovascular bundles are in such close proximity to the posterior lateral prostate. In a study by Stock et al. [29], the effect of multiple pretreatment and treatment factors on potency was analyzed in 416 patients treated with both 125I and 103Pd implantation without external beam irradiation. D90 values had a signi®cant impact on potency. Those patients receiving higher doses of radiation (D90 160 Gy for 125I or 100 Gy for 103Pd) had lower potency preservation (58% at 6 years) than those receiving lower doses (64% at 6 years; p 0:02). Of all the factors that affected potency, only the patient's pre-treatment potency status and the delivered dose (D90) signi®cantly impacted preservation of erectile function in multivariate analysis [29]. 3.5. Rectal toxicity Due to the close proximity of the posterior prostate to the anterior rectal wall there exists a risk of inducing
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radiation changes in the rectum secondary to prostate brachytherapy. The ®rst study to explore the relationship of radiation dose to rectal morbidity following brachytherapy was reported by Wallner et al. [28]. This study used postimplant dosimetry following 125I brachytherapy in 45 patients to calculate anterior rectal wall surface area doses. There was a relationship between developing rectal morbidity and increasing surface area dose. Patients with RTOG grade 1±2 complications had an average of 17 mm2 of their rectal wall irradiated to >100 Gy compared to 11 mm2 for patients without rectal morbidity ( p 0:02) [28]. Merrick et al. [17] analyzed 45 patients treated with either 125I or 103Pd seeds with or without external beam irradiation. An obturator was placed in the rectum during the CT dosimetric analysis to help identify the rectal wall. The recommendation of the study was to keep the length of anterior rectal wall receiving 100 and 120% of the prescribed dose at approximately 10 and 5 mm, respectively, in order to limit the incidence of mild self limited proctitis at 9% [30]. A more practical and useful method of calculating rectal doses from the dosimetric evaluation was described by Snyder et. al. [31]. This technique utilized a rectal dose volume histogram analysis. The rectum volume was de®ned by outlining an inner and outer rectal wall on CT from 9 mm above the seminal vesicles to 9 mm below the prostate. The absolute amount of rectal tissue, measured in cubic centimeters, receiving different doses of radiation was correlated with the risk of developing rectal bleeding. Patients were followed from 12 to 61 (median 28) months after implant. The results of 212 patients treated with 125I implantation revealed that the development of proctitis was signi®cantly volume-dependent for a given dose. The prescription dose (160 Gy) delivered to 1.3 cm3 of rectal tissue resulted in a 5% rate of proctitis at 5 years versus 18% for volumes >1.3 cm3 (p 0:001). As the rectal volume receiving the prescription dose increased, so did the proctitis rate: 0% for 0.8 cm3; 7% for 0.8±1.3 cm3; 8% for 1.3±1.8 cm3; 24% for 1.8± 2.3 cm3, and 25.5% for >2.3 cm3 [31]. 4. Discussion Post-implant dosimetry is crucial in establishing the dose delivered from the implant. Although the implant procedure is over at the time of the dosimetric analysis, the ®ndings from this analysis can be very important. Poor quality implants can be potentially supplemented
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with another implant or external beam irradiation. Dosimetry information has been correlated with tumor control and morbidity. Stock et al. [16] demonstrated a good correlation between D90 values and biochemical control. Doses delivered to the urethra as well the prostate are related to the development of both acute and long-term urinary morbidity [23,28]. Multiple studies have shown that the dose delivered to the rectum is associated with the risk of developing radiation proctitis [28,30,31]. In addition, the D90 has been shown to impact the development of impotency following brachytherapy [29]. The information obtained from these studies can be used to help establish dose goals and tolerance information. Unfortunately, much of this information is only obtained after the implant is complete. Future developments will utilize this information to help improve implant quality in the operating room. A new concept in prostate brachytherapy is real-time intraoperative planning. This technique involves obtaining dosimetric information real-time as the implant is being performed. This would allow physicians to use dosimetric feedback to help modify the implant as it is being performed. Information obtained
from post-implant dosimetric correlation with clinical outcomes can be used intraoperatively to de®ne optimal dose delivery and normal tissue dose tolerance. An intraoperative planning system has been developed using the real-time ultrasound guided technique [32,33]. Dosimetry information obtained intraoperatively using this system has been shown to correlate well with the traditional 1-month CT-based dosimetric analysis [34]. 5. Conclusions Post-implant CT based dosimetry is an essential component of prostate brachytherapy. It is the only method of assessing the actual dose delivered to the prostate and normal surrounding structures. Analyses of dosimetry results have provided valuable information for de®ning optimal doses for tumor control and tolerance doses to limit treatment-related morbidity. Future development in post-implant and intraoperative dosimetry will continue to improve permanent prostate brachytherapy as a safe and effective treatment for prostate cancer.
References [1] Deblasio D, Hilaris B, Nori D, Fuks Z, Whitmore W, Fair W, Anderson L. Permanent interstital implantation of prostatic cancer in the 1980s. Endocur Hypertherm Oncol 1988;4:193±201. [2] Morton JD, Peschel RE. Iodine-125 implants vs. external beam therapy for stages A2, B, C prostate canceer. Int J Radiat Oncol Biol Phys 1988;14:1152±3. [3] Fuks Z, Leibel S, Wallner K, Begg CB, Fair WR, Anderson LL, et al. The effect of local control on metastatic dissemination in carcinoma of the prostate: Long-term results in patients treated with I-125 implantation. Int J Radiat Oncol Biol Phys 1991;21:537±47. [4] Roy JN, Wallner KE, Harrington PJ, Ling CC, Anderson LL. CTbased evaluation method for permanent implants: Application to prostate. Int J Radiat Oncol Biol Phys 1993;26:163±9. [5] Stone NN, Stock RG, DeWyngaert JK, Tabert A. Prostate brachytherapy: Improvements in prostate volume measurements and dose distribution using interactive ultrasound guided implantation and three-dimensional dosimetry. Radiat Oncol Invest 1995;3:185±95. [6] Nag S, Bice W, DeWyngaert K, Prestidge B, Stock R, Yu Y. American Brachytherapy guidelines for post-implant dosimetry for prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000;46:221± 30. [7] Yu Y, Anderson LL, Li Z, Mellenberg DE, Nath R, Schell MC, et al. Permanent prostate seed implant brachytherapy. Report of the American Association of Physicists in Medicine Task Group No. 64. Med Phys 1999;26:2054±76. [8] Ash D, Flynn A, Batterman J, de Reijke T, Lavagnini P, Blank L. ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol 2000;57:315± 21. [9] Merrick GS, Butler WM, Dorsey AT, Lief JH. The dependence of
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prostate post-implant dosimetric quality on CT volume determination. Int J Radiat Oncol Biol Phys 1999;44:1111±7. Stock RG, Stone NN, Lo YC, Malhado N, Kao J, DeWyngaert JK. Post-implant dosimetry for I-125 prostate implants: De®ntions and factors affecting outcome. Int J Radiat Oncol Biol Phys 2000;48:899±906. Waterman FM, Yue N, Corn BW, Dicker AP. Edema associated with I-125 or Pd-103 prostate brachytherapy and its impact on postimplant dosimetry: An analysis based on serial CT acquisition. Int J Radiat Oncol Biol Phys 1998;41:1069±77. Moerland MA, Wijrdeman HK, Beersma R, Bakker CJ, Batterman JJ. Evaluation of permanent I-125 prostate implants using radiography and magnetic resonance imaging. Int J Radiat Oncol Biol Phys 1997;37:927±33. Narayana V, Robertson PL, Pu A. Impact of differences in ultrasound and computed tomography volumes on treatment planning of permanent prostate implants. Int J Radiat Oncol Biol Phys 1997;37:1181±5. Prestidge BR, Bice WS, Kiefer EJ, Prete JJ. Timing of computed tomography-based post-implant assessment following permanent transperineal prostate brachytherapy. Int J Radiat Oncol Biol Phys 1998;40:1111±5. Merrick GS, Butler WM, Dorsey AT. In¯uence of timing on the dosimetric analysis of transperineal ultrasound-guided prostatic conformal brachytherapy. Radiat Oncol Invest 1998;6:182±90. Stock RG, Stone NN, Tabert A, Iannuzzi C, DeWyngaert JK. A doseresponse study for I-125 prostate implants. Int J Radiat Oncol Biol Phys 1998;41:101±8. Merrick GS, Butler WM, Dorsey AT, Lief JH. Potential role of various dosimetric quality indicators in prostate brachytherapy. Int J Radiat Oncol Phys 1999;44:717±24.
R.G. Stock, N.N. Stone / European Urology 41 (2002) 434±439 [18] Willins J, Wallner K. CT based dosimetry for transperineal I-125 prostate brachytherapy. Int J Radiat Oncol Biol Phys 1997;39:347± 53. [19] Narayana V, Roberson PL, Win®eld RJ, Kessler ML, McLaughlin PW. Optimal placement of radioisotopes for permanent prostate implants. Radiology 1996;199:457±60. [20] Dawson JE, Wu T, Roy T, Kim H. Dose effects of seeds placement deviations from pre-planned positions in ultrasound guided prostate implants. Radiother Oncol 1993;32:268±70. [21] Roberson PL, Narayana V, McShan RJ, Win®eld RJ, McLaughlin PW. Source placement error for permanent implant of the prostate. Med Phys 1997;24:251±7. [22] Yu Y, Waterman FM, Suntharalingam N, Schulsinger A. Limitations of the minimum peripheral dose as a parameter for dose speci®cation in permanent 125I prostate implants. Int J Radiat Oncol Biol Phys 1996;34:717±25. [23] Stock RG, Stone NN, Dahlal M, Lo YC. What is the optimal dose for I-125 prostate implants: A dose response analysis of biochemical control, post-treatment prostate biopsies and long-term urinary symptoms. Int J Radiat Oncol Biol Phys 2000;48(suppl):149. [24] Desai JD, Stock RG, Stone NN, Iannuzzi C, DeWyngaert JK. Acute urinary morbidity following I-125 interstitial implantation of the prostate gland. Radiat Oncol Invest 1998;6:135±41. [25] Lee WR, McQuellon RP, Harris-Henderson K, Case LD, McCullough DL. A preliminary analysis of health-related quality of life in the ®rst year after permanent source interstitial brachytherapy (PIB) for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2000;46:77±81. [26] Merrick GS, Butler WM, Lief JH, Dorsey AT. Temporal resolution of
Editorial Comment
Gunnar Aus, JoÈnkoÈping, Sweden An increasing number of patients with low and intermediate risk, localized prostate cancer are today offered radiation therapy with permanent seed implants. Patients are attracted by the minimal invasive technique and the possibility to have a potentially curative treatment delivered as a single-session, outpatient procedure. Reported outcomes from center of excellence are encouraging with results comparable to those obtained by radical prostatectomy or modern 3-D conformal external beam radiotherapy. However, permanent seed implantation is a delicate procedure. All members of the brachytherapy team need to pay attention to details in order to achieve repeatable good implants with the goal of maintaining the combination of good treatment results and low complication rates. The authors of the present article have elegantly underlined how the outcome of the post-implant dosimetry affects both oncological outcome and treatmentrelated side effects of permanent seed brachytherapy. It is clear that the post-implant dosimetry is one of the early benchmarks which may be used when the brachytherapy team aims to judge the quality of their
[27] [28] [29] [30] [31]
[32]
[33] [34]
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urinary morbidity following prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000;47:121±8. Gelblum DY, Potters L, Ashley R, Waldbaum R, Wang XH, Leibel S. Urinary morbidity following ultrasound-guided transperineal prostate seed implantation. Int J Radiat Oncol Biol Phys 1999;45:59±67. Wallner K, Roy J, Harrison L. Dosimetry guidelines to minimize urethral and rectal morbidity following transperineal I-125 prostate brachytherapy. Int J Radiat Oncol Biol Phys 1995;32:465±71. Stock RG, Kao J, Stone NN. Penile erectile function following permanent radioactive seed implantation for the treatment of prostate cancer. J Urol 2001;165:436±9. Merrick GS, Butler WM, Dorsey AT, Lief JH, Walbert HL, Blatt HJ. Rectal dosimetric analysis following prostate brachytherapy. Int J Radiat Oncol Biol Phys 1999;43:1021±7. Snyder KM, Stock RG, Hong SM, Lo YC, Stone NN. De®ning the risk of developing grade 2 proctits following (125)I prostate brachytherapy using a rectal dose-volume histogram analysis. Int J Radiat Oncol Biol Phys 2001;50:335±41. Stock RG, Stone NN, Wesson MF, DeWyngaert JK. A modi®ed technique allowing interactive ultrasound-guided three-dimensional transperineal prostate implantation. Int J Radiat Oncol Biol Phys 1995;32:219±25. Stock RG, Stone NN, Lo TC. Intraoperative dosimetric representation of the real- time ultrasound-guided prostate implant. Tech Urol 2000;6:95±8. Lo YC, Stock RG, Hong S, Stone NN. Prospective comparison of intraoperative real-time to post-implant dosimetry in patients preceiving prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000;48(suppl):359.
implant procedures. This procedure should thus be an obligatory part of all permanent seed implant programs, both for quality control and learning purposes. The major problem with the presented technique is highly operator dependent. Outlining of the prostate on the CT scans is at times dif®cult and the outcome of the post-implant is highly related to this. The ®gure provided in the article is taken form the mid-gland where the prostate borders most often are readily seen. However, contouring of the prostate at the base and apex of the prostate may be much more dif®cult and detection of cold `spots' at these points may be an enigma. What whole-mount step-sections is for radical prostatectomy, post-implant dosimetry should be for permanent seed implants. The above-mentioned limitations mean that the postimplant dosimetry procedure may be subject to some bias. One way to limit the impact of the operator dependence is to send, from time to time, some post-implant CT scans to a totally independent reviewer for quality assurance. As pointed out by the authors, intraoperative dosimetry, with recognition of the already placed seeds on ultrasound, may be the procedure of the near future as it allows a poor implant to be corrected directly.
European Urology 41 (2002) 434±439
Importance of Post-Implant Dosimetry in Permanent Prostate Brachytherapy Richard G. Stocka,*, Nelson N. Stoneb a
Department of Radiation Oncology, Mount Sinai School of Medicine, Box 1236, 1184 5th Avenue, New York, NY 10025, USA Department of Urology, Mount Sinai School of Medicine, New York, NY, USA
b
Accepted 15 June 2001
Abstract Objective: Post-implant dosimetry has become the gold standard for implant evaluation and it is recommended that it be performed on all patients undergoing prostate brachytherapy. The technique, results and correlation with clinical outcomes will be presented. Methods: The method and outcomes of post-implant dosimetry are explored by outlining the experience at the Mount Sinai Medical Center, New York, as well as reviewing the literature. The most accurate time to perform postimplant dosimetry is 1 month after implant. Computed tomography (CT)-based dosimetry is currently the best available technique for performing this analysis. The technique involves taking 3-mm abutting CT slices throughout the implanted area. The prostate and normal structures are outline on the CT slices. These structures are recreated in three dimensions. Dose volume histograms (DVH) are created and allow the dose to these organs to be quanti®ed. Results: The relationship between dosimetric ®ndings and clinical outcomes has been established. The dose delivered to 90% of the prostate on DVH (D90) has been correlated to prostate-speci®c antigen (PCA) control and post-treatment biopsy results. D90 values of 140 Gy have been associated with improved biochemical control and lower positive post-treatment biopsy results. Doses derived from the dosimetric analysis to prostate, urethra and rectum have been correlated with the development of acute and chronic urinary morbidity, sexual potency and rectal morbidity. Future initiatives involve performing dosimetric calculations intraoperatively at the time of the implant. Conclusions: Post-implant CT-based dosimetry is an essential component of prostate brachytherapy. It is the only method of assessing the actual dose delivered to the prostate and normal surrounding structures. Future development in post-implant and intraoperative dosimetry will continue to improve permanent prostate brachytherapy as a safe an effective treatment for prostate cancer. # 2002 Published by Elsevier Science B.V. Keywords: Prostate cancer; Brachytherapy; Dosimetry 1. Introduction The lessons learned from the retropubic era of prostate brachytherapy are that implant quality can greatly affect treatment outcomes. The inadequate technology available at that time resulted in poor seed distribution throughout the prostate gland. This led to higher tumor recurrence rates compared to other therapeutic modalities [1,2]. Unfortunately, at that time there did not exist an adequate method for evaluating *
Corresponding author. Tel.: 1-212-241-7502; Fax: 1-212-410-7194. E-mail address: [email protected] (R.G. Stock).
implant quality. The only technique available at that time involved plain X-rays of the pelvis to determine seed locations. Although this process demonstrated the radiation dose distribution around the seeds, there was no way of relating these doses to the actual prostate since the gland was not imaged. Despite these limitations, the total dose delivered by these retropubicly implanted seeds was correlated to local failure as measured by the digital rectal examination [3]. These data highlighted the need for implant quality evaluation and demonstrated the importance of the delivered dose in achieving tumor control. During the advent of the transperineal ultrasound-guided seed implant technique
0302-2838/02/$ ± see front matter # 2002 Published by Elsevier Science B.V. PII: S 0 3 0 2 - 2 8 3 8 ( 0 2 ) 0 0 0 1 8 - 0
R.G. Stock, N.N. Stone / European Urology 41 (2002) 434±439
a newer more accurate method of implant quality evaluation was developed. This new method, known as computed tomography (CT)-based post-implant dosimetry, utilized CT to image the prostate and allowed the location and dose distribution of the seeds to be directly related to the actual prostate [4,5]. Postimplant dosimetry has become the gold standard for implant evaluation and it is recommended by the American Brachytherapy Society, the American Association of Physicists in Medicine and the ESTRO/EAU/ EORTC that it be performed on all patients undergoing permanent prostate brachytherapy [6±8]. The technique and methods of analyzing post-implant dosimetry developed at the Mount Sinai Medical Center, New York, as well as clinical correlations and a literature review will be presented in order to show its crucial role in the continued improvement of prostate brachytherapy. 2. Materials and methods 2.1. Post-implant dosimetry technique The most commonly used and best technique currently available for performing dosimetry is CT-based [6]. The technique developed at the Mount Sinai School of Medicine, New York, NY, is employed by taking 3-mm abutting CT slices throughout the implanted area [5]. On every CT slice, the prostate is contoured. The urethral location is estimated in the majority of cases by comparison with ultrasound images or by the use of a Foley catheter. The inner and outer wall of the bladder and rectum are outlined. The ADAC (Milpitas, CA, USA) pinnacle system is used to perform the dosimetry calculations. Seed locations are identi®ed on every CT slice. The total number of seeds implanted is cross checked with the number of seeds counted on orthogonal X-ray ®lms. All structures are reconstructed in three dimensions and dose distributions to these structures are calculated.
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2.2. Outlining the prostate volume Multiple methods exist for outlining the prostate on the postimplant CT study. Merrick et al. [9] describe three methods: outlining the prostate plus a periprostatic margin; outlining the prostate only which excludes the puborectalis muscles, the periprostatic fat and the periprostatic venous plexus, and superimposing the pre-planning ultrasound volume magni®ed to conform to the magni®cation factor of the post-implant CT. They found little differrence in the dosimetric ®ndings using the different volume approaches [9]. The Mount Sinai technique utilizes the features of the ADAC pinnacle system to enhance the accuracy of the volume determination. The image is enlarged to exclude all surrounding structures beyond the bladder, prostate, seminal vesicles and rectum. The CT images are set at a window of 400 and a level of 800 to enhance soft tissue delineation. The prostate is outlined without a margin. The periprostatic venous plexus and fat as well as surrounding musculature are excluded (Fig. 1). This technique has resulted in a good correlation between the ultrasound volume and the CT volume. In a study of 297 125I post-implant dosimetry analyses, the CT/ultrasound volume ratios were between 0.8 and 1.2 in 74% of cases [10]. 2.3. Timing of post-implant dosimetry Since implantation can cause swelling and edema within the gland, which can alter the prostate volume, the timing of the implant analysis is important. Prostate volume increases on average have ranged from 20 to 50% [11±15]. The half-life of this edema has been reported to be about 10 days [11]. Although performing dosimetry 1 day after implantation may be the most convenient, the edema on this day has been reported to cause an average increase in prostate volume of 52%. This will result in an approximate 10% decrease in the calculated delivered dose [11]. For this reason, the 1-month time has been used to perform dosimetry. The dose calculated at 1 month has been shown to most accurately represent the delivered dose over the life of the implant [14]. It is felt that the most reproducible results will be obtained by performing dosimetry at this time [6]. 2.4. Dosimetry analysis The information obtained from the post-implant CT scan can be used to generate dose volume histograms (DVH). These plots
Fig. 1. Transverse CT image of implanted prostate: (a) without contoured prostate; (b) with prostate contoured.
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describe the dose distribution of the prostate. Using the DVH, the amount of prostate receiving a given dose of radiation can be obtained. Terms such as D100, D90 and D80 refer to the amount of dose delivered to 100, 90 and 80%, respectively, of the prostate volume as outlined on the CT slices. Conversely terms such as V100, V150 refer to the volume of the prostate receiving 100 and 150%, respectively, of the prescription dose. Since there may be small errors in outlining the prostate as well as small areas within the prostate that are underdosed, the term D90 has been adopted as the best description of delivered dose [6,7]. In addition, the D90 is the only dose parameter that has been correlated to the prostate-speci®c antigen (PSA) response [16]. The D100 is a poor dose description since it is extremely sensitive to the volume drawn as well as any areas, no matter how small, which are underdosed. In addition D100 has been shown to poorly correlate to the D90 [10,17].
3. Results Most available information on post-implant dosimetry comes from studies on 125I prostate seed implantation. There is currently little data available on dosimetry following 103Pd implants. Extrapolations of the data on 125 I dosimetry to 103Pd dosimetry are dif®cult due to the inherent differences in dose rate, half life and tissue attenuation between the two isotopes. There are few reports on post-implant dosimetry results with large numbers of patients. Many analyses have been used to show that the exact pre-planned dose coverage used for a pre-planning technique can rarely be achieved [18±22]. Willins and Wallner [18] showed that on average only 84% (76±92%) of the target was covered by the prescription dose of 140 Gy. These reports emphasize the importance of the post-implant analysis since the pre-plan will rarely represent the actual delivered dose. The largest dosimtery report comes from Stock et al. [10]. In this study, 297 patients implanted using a realtime ultrasound-guided technique with 125I alone (prescription dose 160 Gy) without external beam irradiation underwent 1 month CT-based dosimetry. All prostate volumes were outline by one person. In this study, the median D100, D95, D90 and D80 were 102, 157, 176 and 199 Gy, respectively. In addition, the median V100 and V150 were 94 and 56%, respectively. The study also showed that factors associated with more precise implantation such as decreased postimplant edema, newer technology and increased number of seeds would lead to higher D90 values [10]. 3.1. Clinical correlation 3.1.1. PSA and biopsy data The ®rst clinical correlation of dosimetry results to PSA control was reported by Stock et al. [23]. In this
study, 134 patients with T1±T2 prostate cancer underwent 125I seed implantation alone. Since these patients were treated from 1990 to 1996 and changes in technique and the amount of activity implanted per volume were made over this time, different prostatic doses were delivered. Based on these doses, a dose-response analysis was performed. The study revealed that those patients receiving D90 values of 140 Gy had an improved biochemical control rate (PSA 1.0 ng/ ml) of 92% at 4 years compared to 68% for those patients with D90 values of <140 Gy ( p 0:02) [13]. An update of these data continues to support a close relationship between delivered dose (D90) and tumor control. In 180 patients, freedom from PSA failure (FFPF) at 6 years was 60% for D90 <140 Gy, 97% for 140±160 Gy, 98% for 160±180 Gy, and 95% for >180 Gy (p 0:0025). Overall, patients with doses of <140 Gy (median follow-up 66 months) had a FFPF of 60% compared to 96% for patients with doses of 140 Gy (median follow-up 35 months; p 0:0002) [23]. In addition, this type of dose response was demonstrated with respect to 2-year post-treatment prostate biopsies. In 113 patients, positive biopsies were found in 23% for doses of <140 Gy, 21% for 140±160 Gy, 10% for 160±180 Gy, and 8% for 180 Gy. Overall, biopsies were positive in 22% for doses of <160 Gy versus 9% for 160 Gy ( p 0:05) [23]. 3.2. Acute urinary morbidity Acute urinary symptoms such as frequency, dysuria, urgency, nocturia and weak stream are common side effects of prostate brachytherapy. These symptoms usually occur 1±2 weeks after implantation and can last for months following the procedure. Most acute urinary symptoms subside by 1 year following brachytherapy [24±27]. In a study by Desai et al. [24], acute urinary symptoms as assessed by the international prostate symptom score (IPSS) were correlated to dosimetric parameters in 117 patients treated with 125 I prostate seed implantation. This study found that increasing doses delivered to the prostate resulted in increased urinary symptoms. The D90 correlated well with the total IPSS ( p < 0:001). In addition, the dose delivered to 5 cm2 of urethra correlated with the maximal frequency score ( p 0:04) [24]. Others have not found DVH parameters to affect acute morbidity [26,27]. 3.3. Chronic urinary morbidity Fibrosis and necrosis that can occur within the prostate and urethra secondary to irradiation can cause chronic urinary morbidity. Typically, these late
R.G. Stock, N.N. Stone / European Urology 41 (2002) 434±439
radiation changes develop 18 months or longer following implantation. The ®rst study to examine the relationship between urinary morbidity and dosimetric parameters was by Wallner et al. [28]. In this study, the dose delivered to the urethra in 45 patients treated with 125I seed implantation was correlated to the radiation therapy and oncology group (RTOG) morbidity scale. This study found an association with the length of urethra receiving 400 Gy and the RTOG morbidity score. Patients with RTOG grades 0±1 urinary morbidity had an average of 1 cm of urethra irradiated to >400 Gy compared to 2 cm for patients with grade 2±3 morbidity (p 0:07) [28]. In a larger study by Stock et al. [23], the relationship between prostate dose and late urinary morbidity was assessed in 276 patients treated with 125I seed implantation and followed from 18 to 108 (median 34) months. The relationship between prostate D90 and the last IPSS was examined by comparing the patients' pre-treatment IPSS to their last follow-up IPSS in different D90 dose groups. There were minimal changes in IPSS seen in the dose groups <140, 140±160, and 160±180 Gy. For patients receiving D90 of >180 Gy, there was signi®cant worsening of the mean scores from 0.5 to 1.0 ( p 0:002) for emptying, 0.76 to 1.29 ( p 0:004) for weak stream, 0.24±0.51 ( p 0:009) for straining, 1.55 to 1.82 ( p 0:05) for nocturia, and 6.3±8.45 ( p 0:0009) for total score [23]. These data suggest that a higher prostatic dose of >180 Gy may lead to increased late urinary symptoms. 3.4. Sexual potency Theoretically, the dose delivered to the prostate could have a signi®cant impact on erectile function preservation, since the neurovascular bundles are in such close proximity to the posterior lateral prostate. In a study by Stock et al. [29], the effect of multiple pretreatment and treatment factors on potency was analyzed in 416 patients treated with both 125I and 103Pd implantation without external beam irradiation. D90 values had a signi®cant impact on potency. Those patients receiving higher doses of radiation (D90 160 Gy for 125I or 100 Gy for 103Pd) had lower potency preservation (58% at 6 years) than those receiving lower doses (64% at 6 years; p 0:02). Of all the factors that affected potency, only the patient's pre-treatment potency status and the delivered dose (D90) signi®cantly impacted preservation of erectile function in multivariate analysis [29]. 3.5. Rectal toxicity Due to the close proximity of the posterior prostate to the anterior rectal wall there exists a risk of inducing
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radiation changes in the rectum secondary to prostate brachytherapy. The ®rst study to explore the relationship of radiation dose to rectal morbidity following brachytherapy was reported by Wallner et al. [28]. This study used postimplant dosimetry following 125I brachytherapy in 45 patients to calculate anterior rectal wall surface area doses. There was a relationship between developing rectal morbidity and increasing surface area dose. Patients with RTOG grade 1±2 complications had an average of 17 mm2 of their rectal wall irradiated to >100 Gy compared to 11 mm2 for patients without rectal morbidity ( p 0:02) [28]. Merrick et al. [17] analyzed 45 patients treated with either 125I or 103Pd seeds with or without external beam irradiation. An obturator was placed in the rectum during the CT dosimetric analysis to help identify the rectal wall. The recommendation of the study was to keep the length of anterior rectal wall receiving 100 and 120% of the prescribed dose at approximately 10 and 5 mm, respectively, in order to limit the incidence of mild self limited proctitis at 9% [30]. A more practical and useful method of calculating rectal doses from the dosimetric evaluation was described by Snyder et. al. [31]. This technique utilized a rectal dose volume histogram analysis. The rectum volume was de®ned by outlining an inner and outer rectal wall on CT from 9 mm above the seminal vesicles to 9 mm below the prostate. The absolute amount of rectal tissue, measured in cubic centimeters, receiving different doses of radiation was correlated with the risk of developing rectal bleeding. Patients were followed from 12 to 61 (median 28) months after implant. The results of 212 patients treated with 125I implantation revealed that the development of proctitis was signi®cantly volume-dependent for a given dose. The prescription dose (160 Gy) delivered to 1.3 cm3 of rectal tissue resulted in a 5% rate of proctitis at 5 years versus 18% for volumes >1.3 cm3 (p 0:001). As the rectal volume receiving the prescription dose increased, so did the proctitis rate: 0% for 0.8 cm3; 7% for 0.8±1.3 cm3; 8% for 1.3±1.8 cm3; 24% for 1.8± 2.3 cm3, and 25.5% for >2.3 cm3 [31]. 4. Discussion Post-implant dosimetry is crucial in establishing the dose delivered from the implant. Although the implant procedure is over at the time of the dosimetric analysis, the ®ndings from this analysis can be very important. Poor quality implants can be potentially supplemented
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with another implant or external beam irradiation. Dosimetry information has been correlated with tumor control and morbidity. Stock et al. [16] demonstrated a good correlation between D90 values and biochemical control. Doses delivered to the urethra as well the prostate are related to the development of both acute and long-term urinary morbidity [23,28]. Multiple studies have shown that the dose delivered to the rectum is associated with the risk of developing radiation proctitis [28,30,31]. In addition, the D90 has been shown to impact the development of impotency following brachytherapy [29]. The information obtained from these studies can be used to help establish dose goals and tolerance information. Unfortunately, much of this information is only obtained after the implant is complete. Future developments will utilize this information to help improve implant quality in the operating room. A new concept in prostate brachytherapy is real-time intraoperative planning. This technique involves obtaining dosimetric information real-time as the implant is being performed. This would allow physicians to use dosimetric feedback to help modify the implant as it is being performed. Information obtained
from post-implant dosimetric correlation with clinical outcomes can be used intraoperatively to de®ne optimal dose delivery and normal tissue dose tolerance. An intraoperative planning system has been developed using the real-time ultrasound guided technique [32,33]. Dosimetry information obtained intraoperatively using this system has been shown to correlate well with the traditional 1-month CT-based dosimetric analysis [34]. 5. Conclusions Post-implant CT based dosimetry is an essential component of prostate brachytherapy. It is the only method of assessing the actual dose delivered to the prostate and normal surrounding structures. Analyses of dosimetry results have provided valuable information for de®ning optimal doses for tumor control and tolerance doses to limit treatment-related morbidity. Future development in post-implant and intraoperative dosimetry will continue to improve permanent prostate brachytherapy as a safe and effective treatment for prostate cancer.
References [1] Deblasio D, Hilaris B, Nori D, Fuks Z, Whitmore W, Fair W, Anderson L. Permanent interstital implantation of prostatic cancer in the 1980s. Endocur Hypertherm Oncol 1988;4:193±201. [2] Morton JD, Peschel RE. Iodine-125 implants vs. external beam therapy for stages A2, B, C prostate canceer. Int J Radiat Oncol Biol Phys 1988;14:1152±3. [3] Fuks Z, Leibel S, Wallner K, Begg CB, Fair WR, Anderson LL, et al. The effect of local control on metastatic dissemination in carcinoma of the prostate: Long-term results in patients treated with I-125 implantation. Int J Radiat Oncol Biol Phys 1991;21:537±47. [4] Roy JN, Wallner KE, Harrington PJ, Ling CC, Anderson LL. CTbased evaluation method for permanent implants: Application to prostate. Int J Radiat Oncol Biol Phys 1993;26:163±9. [5] Stone NN, Stock RG, DeWyngaert JK, Tabert A. Prostate brachytherapy: Improvements in prostate volume measurements and dose distribution using interactive ultrasound guided implantation and three-dimensional dosimetry. Radiat Oncol Invest 1995;3:185±95. [6] Nag S, Bice W, DeWyngaert K, Prestidge B, Stock R, Yu Y. American Brachytherapy guidelines for post-implant dosimetry for prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000;46:221± 30. [7] Yu Y, Anderson LL, Li Z, Mellenberg DE, Nath R, Schell MC, et al. Permanent prostate seed implant brachytherapy. Report of the American Association of Physicists in Medicine Task Group No. 64. Med Phys 1999;26:2054±76. [8] Ash D, Flynn A, Batterman J, de Reijke T, Lavagnini P, Blank L. ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol 2000;57:315± 21. [9] Merrick GS, Butler WM, Dorsey AT, Lief JH. The dependence of
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R.G. Stock, N.N. Stone / European Urology 41 (2002) 434±439 [18] Willins J, Wallner K. CT based dosimetry for transperineal I-125 prostate brachytherapy. Int J Radiat Oncol Biol Phys 1997;39:347± 53. [19] Narayana V, Roberson PL, Win®eld RJ, Kessler ML, McLaughlin PW. Optimal placement of radioisotopes for permanent prostate implants. Radiology 1996;199:457±60. [20] Dawson JE, Wu T, Roy T, Kim H. Dose effects of seeds placement deviations from pre-planned positions in ultrasound guided prostate implants. Radiother Oncol 1993;32:268±70. [21] Roberson PL, Narayana V, McShan RJ, Win®eld RJ, McLaughlin PW. Source placement error for permanent implant of the prostate. Med Phys 1997;24:251±7. [22] Yu Y, Waterman FM, Suntharalingam N, Schulsinger A. Limitations of the minimum peripheral dose as a parameter for dose speci®cation in permanent 125I prostate implants. Int J Radiat Oncol Biol Phys 1996;34:717±25. [23] Stock RG, Stone NN, Dahlal M, Lo YC. What is the optimal dose for I-125 prostate implants: A dose response analysis of biochemical control, post-treatment prostate biopsies and long-term urinary symptoms. Int J Radiat Oncol Biol Phys 2000;48(suppl):149. [24] Desai JD, Stock RG, Stone NN, Iannuzzi C, DeWyngaert JK. Acute urinary morbidity following I-125 interstitial implantation of the prostate gland. Radiat Oncol Invest 1998;6:135±41. [25] Lee WR, McQuellon RP, Harris-Henderson K, Case LD, McCullough DL. A preliminary analysis of health-related quality of life in the ®rst year after permanent source interstitial brachytherapy (PIB) for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2000;46:77±81. [26] Merrick GS, Butler WM, Lief JH, Dorsey AT. Temporal resolution of
Editorial Comment
Gunnar Aus, JoÈnkoÈping, Sweden An increasing number of patients with low and intermediate risk, localized prostate cancer are today offered radiation therapy with permanent seed implants. Patients are attracted by the minimal invasive technique and the possibility to have a potentially curative treatment delivered as a single-session, outpatient procedure. Reported outcomes from center of excellence are encouraging with results comparable to those obtained by radical prostatectomy or modern 3-D conformal external beam radiotherapy. However, permanent seed implantation is a delicate procedure. All members of the brachytherapy team need to pay attention to details in order to achieve repeatable good implants with the goal of maintaining the combination of good treatment results and low complication rates. The authors of the present article have elegantly underlined how the outcome of the post-implant dosimetry affects both oncological outcome and treatmentrelated side effects of permanent seed brachytherapy. It is clear that the post-implant dosimetry is one of the early benchmarks which may be used when the brachytherapy team aims to judge the quality of their
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[32]
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urinary morbidity following prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000;47:121±8. Gelblum DY, Potters L, Ashley R, Waldbaum R, Wang XH, Leibel S. Urinary morbidity following ultrasound-guided transperineal prostate seed implantation. Int J Radiat Oncol Biol Phys 1999;45:59±67. Wallner K, Roy J, Harrison L. Dosimetry guidelines to minimize urethral and rectal morbidity following transperineal I-125 prostate brachytherapy. Int J Radiat Oncol Biol Phys 1995;32:465±71. Stock RG, Kao J, Stone NN. Penile erectile function following permanent radioactive seed implantation for the treatment of prostate cancer. J Urol 2001;165:436±9. Merrick GS, Butler WM, Dorsey AT, Lief JH, Walbert HL, Blatt HJ. Rectal dosimetric analysis following prostate brachytherapy. Int J Radiat Oncol Biol Phys 1999;43:1021±7. Snyder KM, Stock RG, Hong SM, Lo YC, Stone NN. De®ning the risk of developing grade 2 proctits following (125)I prostate brachytherapy using a rectal dose-volume histogram analysis. Int J Radiat Oncol Biol Phys 2001;50:335±41. Stock RG, Stone NN, Wesson MF, DeWyngaert JK. A modi®ed technique allowing interactive ultrasound-guided three-dimensional transperineal prostate implantation. Int J Radiat Oncol Biol Phys 1995;32:219±25. Stock RG, Stone NN, Lo TC. Intraoperative dosimetric representation of the real- time ultrasound-guided prostate implant. Tech Urol 2000;6:95±8. Lo YC, Stock RG, Hong S, Stone NN. Prospective comparison of intraoperative real-time to post-implant dosimetry in patients preceiving prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000;48(suppl):359.
implant procedures. This procedure should thus be an obligatory part of all permanent seed implant programs, both for quality control and learning purposes. The major problem with the presented technique is highly operator dependent. Outlining of the prostate on the CT scans is at times dif®cult and the outcome of the post-implant is highly related to this. The ®gure provided in the article is taken form the mid-gland where the prostate borders most often are readily seen. However, contouring of the prostate at the base and apex of the prostate may be much more dif®cult and detection of cold `spots' at these points may be an enigma. What whole-mount step-sections is for radical prostatectomy, post-implant dosimetry should be for permanent seed implants. The above-mentioned limitations mean that the postimplant dosimetry procedure may be subject to some bias. One way to limit the impact of the operator dependence is to send, from time to time, some post-implant CT scans to a totally independent reviewer for quality assurance. As pointed out by the authors, intraoperative dosimetry, with recognition of the already placed seeds on ultrasound, may be the procedure of the near future as it allows a poor implant to be corrected directly.