Bradley R. Prestidge

THE AMERICAN BRACHYTHERAPY SOCIETY RECOMMENDATIONS FOR PERMANENT PROSTATE BRACHYTHERAPY POSTIMPLANT DOSIMETRIC ANALYSIS

PURPOSE The purpose of this report is to establish guidelines for postimplant dosimetric analysis of permanent prostate brachytherapy. METHODS Members of the American Brachytherapy Society (ABS) with expertise in prostate dosimetry evaluation performed a literature review and supplemented with their clinical experience formulated guidelines for performing and analyzing postimplant dosimetry of permanent prostate brachytherapy. RESULTS The ABS recommends that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy for optimal patient care. At present, computed tomography (CT)-based dosimetry is recommended, based on availability cost and the ability to image the prostate as well as the seeds. Additional plane radiographs should be obtained to verify the seed count. Until the ideal postoperative interval for CT scanning has been determined, each center should perform dosimetric evaluation of prostate implants at a consistent postoperative interval. This interval should be reported. Isodose displays should be obtained at 50%, 80%, 90%, 100%, 150%, and 200% of the prescription dose and displayed on multiple cross-sectional images of the prostate. A dose-volume histogram (DVH) of the prostate should be performed and the D90 (dose to 90% of the prostate gland) reported by all centers. Additionally, the D80, D100, the fractional V80, V90, V100, V150 and V200 (i.e., the percentage of prostate volume receiving 80%, 90%, 100%, 150%, and 200% of the prescribed dose, respectively), the rectal, and urethral doses should be reported and ultimately correlated with clinical outcome in the research environment. On-line real-time dosimetry, the effects of dose heterogeneity, and the effects of tissue heterogeneity need further investigation. CONCLUSION It is essential that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy. Guidelines were established for the performance and analysis of such dosimetry.

Centralized Multiinstitutional Postimplant Analysis for Interstitial Prostate Brachytherapy

PURPOSE To investigate the feasibility and utility of performing centralized postimplant analysis for transperineal interstitial permanent prostate brachytherapy (TIPPB) by conducting a pilot study that compares the results obtained from 125I implants conducted at five different institutions. METHODS AND MATERIALS Dose-volume histogram (DVH) analysis was performed on 10 postimplant CT scans from each of five institutions. This analysis included the total implanted activity of 125I, ultrasound, and CT volumes of the prostate, target-volume ratios, dose homogeneity quantifiers, prostate dose coverage indices, and rectal doses. As a result of the uncertainty associated with the delineation of the prostatic boundaries on a CT scan, the contours were redrawn by a single, study center physician, and a repeat DVH analysis was performed. This provided the basis for comparison between institutions in terms of implant technique and quality. RESULTS By comparing total activity to preimplant ultrasound volume we clearly demonstrated that differences exist in implant technique among these five institutions. The difficulty associated with determining glandular boundaries on CT scans was apparent, based upon the variability in prostate volumes drawn by the various investigators compared to those drawn by the study center physician. This made no difference, of course, in the TVR or homogeneity quantifiers that are independent of target location. Furthermore, this variability made surprisingly little difference in terms of dose coverage of the prostate gland. Rectal doses varied between institutions according to the various implant techniques. CONCLUSIONS Centralized, outcome-based evaluation of transperineal interstitial permanent prostate brachytherapy is viable and appropriate. Such an approach could be reasonably used in the conduct of multiinstitutional trials used to study the efficacy of the procedure.

The Importance of Local Control in the Treatment of Prostatic Cancer

In a retrospective analysis of 946 patients with prostatic carcinoma treated with external beam radiotherapy between 1958 and 1989 at Stanford University Hospital the 15-year actuarial clinical local control rate was 77.8 +/- 3.3% for Stanford stage T1, 61.3 +/- 4.4% for stage T2 and 64.9 +/- 4.8% for stage T3 disease. Overall, there was improvement in disease-specific survival without a significant alteration in survival in patients who achieved clinical local control. For the 50 Stanford stage T1 cases with local control on clinical examination and a positive post-treatment biopsy a decrease in disease-specific survival was observed. There was no difference in disease-specific survival for comparable stage T2 or T3 cases. In an analysis of patients who underwent ultrasound guided prostatic biopsy performed after irradiation the trend of prostate specific antigen was more important than biopsy results in predicting which patients would have relapse.

Prostate Specific Antigen after Irradiation for Prostatic Carcinoma

The clinical significance of serum prostate specific antigen after primary irradiation for adenocarcinoma of the prostate is uncertain. Between September 1986 and December 1987 serial prostate specific antigen values were determined in 43 patients before and after definitive radiation therapy. The study group included 6 patients with stage T0d, 10 with stage T1, 11 with stage T2 and 16 with stage T3 disease, with a mean pre-treatment prostate specific antigen level of 49.2 +/- 10.8. For all patients the first post-treatment prostate specific antigen level was less than the pre-treatment level. One patient failed locally with recurrent prostatic cancer that invaded the rectum. The 6 patients who failed with symptomatic metastases had an increasing prostate specific antigen level 2 to 7 months before detection of recurrence. Based on the absolute value and trend of the prostate specific antigen, patients were described as being at high, intermediate or low risk for distant metastases. Of 9 high, 6 intermediate and 28 low risk patients 4 (44%), 2 (33%) and 0 (0%) have experienced recurrent disease (p = 0.0025). We conclude that serial post-irradiation prostate specific antigen values may be useful in the early identification of patients at risk for treatment failure.

The clinical significance of a positive post-irradiation prostatic biopsy without metastases

To define the prognostic value of a post-irradiation prostatic biopsy, the outcome of 203 previously irradiated patients who underwent post-treatment biopsy was analyzed. The majority of patients were selected for biopsy based on an abnormal digital rectal exam or elevated prostate specific antigen. Patients with distant metastases found at the time of biopsy were excluded from further analysis. One hundred thirty-nine (139) of these had a positive biopsy and 64 were negative. Those with a positive biopsy tended to present with more locally-advanced (Stage B2/C) tumors (61%) compared to those with negative biopsies (42%). The 10- and 15-year survival and cause-specific survival from the time of initial presentation were similar for both groups. However, those with a negative biopsy had a more favorable survival and cause-specific survival from the time of post-treatment biopsy and were less likely to develop distant metastases than the positive biopsy group. These data suggest that a positive prostatic biopsy is associated with a greater likelihood of subsequent distant relapse and decreased survival following biopsy relative to patients with negative biopsies. Since a positive post-treatment biopsy is more likely among patients presenting with locally-advanced disease, perhaps more aggressive initial therapy (i.e., interstitial boost or hyperthermia) would benefit this subgroup.

Source localization from axial image sets by iterative relaxation of the nearest neighbor criterion

The use of axial image sets has become widely used to localize interstitial brachytherapy sources. One application of this method of localization is to perform post-implant dosimetry following transperineal interstitial permanent prostate brachytherapy (TIPPB) where the target structure and the source locations are displayed on the same image. The design of an appropriate scanning sequence often results in abutting slices of an intermediate slice width (3, 4, or 5 mm). Because a single source may be imaged on more than one slice, the resultant scans always show many more source locations than actual sources implanted. The physicist is then faced with the tedious task of determining which sources appear on more than one slice and deciding which source locations to eliminate from the data set. We have developed an algorithm, similar to one employed by Roy et al., which automates this process by relaxing the nearest neighbor criterion until the number of sources is reduced to either the number of sources implanted or the number counted on a projection radiograph. This paper details this algorithm and the results of its application to phantom studies, comparing to known source locations, as well as clinical studies, comparing to orthogonal film source localization, on a series of ten patients. Phantom studies demonstrate the superiority of the algorithm over orthogonal film reconstruction, locating 100% of the sources within 5 mm of the actual location as compared to 66% for the paired radiographs. The clinical study findings are commensurate with these results, with 72% of the sources on average located within 5 mm of the corresponding source in the other data set. The positive correlation of the quality of the orthogonal film reconstruction results with the quality of the coregistration results suggests that differences in registration between the two data sets may be due primarily to the uncertainties in the orthogonal film reconstruction.

The Observed Variance Between Predicted and Measured Radiation Dose in Breast and Prostate Patients Utilizing an In Vivo Dosimeter

PURPOSE Report the results of using a permanently implantable dosimeter in radiation therapy: determine specific adverse events, degree of migration, and acquire dose measurements during treatment to determine difference between expected and measured dose. METHODS AND MATERIALS The Dose Verification System is a wireless, permanently implantable metal-oxide semiconductor field-effect transistor dosimeter using a bidirectional antenna for power and data transfer. The study cohort includes 36 breast (33 patients received two devices) and 29 prostate (21 patients received two devices) cancer patients. A total of 1,783 and 1,749 daily dose measurements were obtained on breast and prostate patients, respectively. The measurements were compared with the planned expected dose. Biweekly computed tomography scans were obtained to evaluate migration and the National Cancer Institutes Common Toxicity Criteria, version 3, was used to evaluate adverse events. RESULTS Only Grade I/II adverse events of pain and bleeding were noted. There were only four instances of dosimeter migration of >5 mm from known factors. A deviation of > or =7% in cumulative dose was noted in 7 of 36 (19%) for breast cancer patients. In prostate cancer patients, a > or =7% deviation was noted in 6 of 29 (21%) and 8 of 19 (42%) during initial and boost irradiation, respectively. The two patterns of dose deviation were random and systematic. Some causes for these differences could involve organ movement, patient movement, or treatment plan considerations. CONCLUSIONS The Dose Verification System was not associated with significant adverse events or migration. The dosimeter can measure dose in situ on a daily basis. The accuracy and utility of the dose verification system complements current image-guided radiation therapy and intensity-modulated radiation therapy techniques.

Sector analysis of prostate implants.

The analysis of treatment plans generated following prostate implants (post plans) is an essential part of the patients treatment regimen. The results are used to determine the adequacy of the individual implant and, just as importantly, to provide an evaluation of the institutions brachytherapy technique. Compiled post plan results can be used to compare data from different institutions and help determine guidelines that should be established as dosimetric goals. Sector analysis, or spatial dose mapping, is a novel method of analyzing brachytherapy results that has been developed for this purpose. The display of isodose curves provides spatial information pertaining to the dosimetric evaluation of post plans but is an unwieldy tool; ill suited to the creation of general conclusions for comparative efforts. Dose-volume histogram (DVH) analysis is an excellent tool for examining dosimetric results, but the spatial information is lost. Sector analysis bridges the gap between isodose curves and DVH analysis in post plan analysis. To perform sector analysis we divide the gland into three regions in the cranial-caudal direction (base, midgland, and apex) and four regions on each transverse slice (anterior, posterior, left and right). This gives twelve sectors, each identified by its location in the cranial-caudal direction and position on the transverse slice, e.g., posterior midgland. DVH analysis is performed for each region separately and compiled for display. We present an example of the use of this technique wherein we have analyzed a sequential series of 118 implants performed by a single practitioner (BRP) at two institutions over a calendar year. The implants were performed using two different techniques at the two institutions. Sector analysis was used to compare the results of the implants at the two institutions.

Evaluation of hybrid inverse planning and optimization (HIPO) algorithm for optimization in real-time, high-dose-rate (HDR) brachytherapy for prostate

The purpose of this study is to investigate the effectiveness of the HIPO planning and optimization algorithm for real‐time prostate HDR brachytherapy. This study consists of 20 patients who underwent ultrasound‐based real‐time HDR brachytherapy of the prostate using the treatment planning system called Oncentra Prostate (SWIFT version 3.0). The treatment plans for all patients were optimized using inverse dose‐volume histogram–based optimization followed by graphical optimization (GRO) in real time. The GRO is manual manipulation of isodose lines slice by slice. The quality of the plan heavily depends on planner expertise and experience. The data for all patients were retrieved later, and treatment plans were created and optimized using HIPO algorithm with the same set of dose constraints, number of catheters, and set of contours as in the real‐time optimization algorithm. The HIPO algorithm is a hybrid because it combines both stochastic and deterministic algorithms. The stochastic algorithm, called simulated annealing, searches the optimal catheter distributions for a given set of dose objectives. The deterministic algorithm, called dose‐volume histogram–based optimization (DVHO), optimizes three‐dimensional dose distribution quickly by moving straight downhill once it is in the advantageous region of the search space given by the stochastic algorithm. The PTV receiving 100% of the prescription dose (V100) was 97.56% and 95.38% with GRO and HIPO, respectively. The mean dose (Dmean) and minimum dose to 10% volume (D10) for the urethra, rectum, and bladder were all statistically lower with HIPO compared to GRO using the student pair t‐test at 5% significance level. HIPO can provide treatment plans with comparable target coverage to that of GRO with a reduction in dose to the critical structures. PACS number: 87.55.‐X

Ultrasound guided placement of transperineal prostatic afterloading catheters

PURPOSE A new method of performing temporary prostate brachytherapy which does not require an open laparotomy is described. METHODS AND MATERIALS This procedure allows dynamic visualization of the placement of 13-gauge (I-125) or 17-gauge (Ir-192) afterloading catheters into the prostate gland via saggital ultrasound imaging. The image enables visualization of the entire path of the catheter as well as cephalad gland movement. The prostate gland, seminal vesicles, bladder neck, urethra, and rectum are easily identified and implanted, if desired, during the procedure. This procedure has been used in 34 patients as an interstitial boost for locally advanced (T2b, T3) prostatic carcinoma following external beam therapy as a means to safely deliver higher doses to the gland. Another eight patients have undergone this procedure as salvage following failure of prior radical prostatectomy or external beam therapy. RESULTS Very customized dosimetry has been obtained using this technique as a result of the optimal catheter placement achieved under ultrasound guidance, particularly with I-125. Although it is too early to evaluate efficacy, the procedure has been well tolerated and is associated with minimal morbidity to date. CONCLUSION This new procedure seems to be an excellent means of safe delivery of higher doses to the gland compared to conventional external beam therapy. Due to the ability to cover the seminal vesicles as well as the afterloading nature of this procedure, a more customized implant is obtained relative to most permanent techniques, and open laparotomy is not required.