Permanent Prostate Implants Research Articles

Quality of life of patients after permanent prostate brachytherapy in relation to dosimetry: Van Gellekom MPR, Moerland MA, Van Vulpen M, Wijrdeman HK, Battermann JJ, Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands

To investigate changes in quality of life (QoL) after permanent prostate brachytherapy and to correlate these changes with postimplant dosimetry based on magnetic resonance (MR) images. For this study, 127 patients with low-stage prostate cancer and treated with brachytherapy received a QoL questionnaire at five time points: before treatment and at 4 weeks, 6 months, 1 year, and 2 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer (EORTC) core questionnaire, the tumor-specific EORTC prostate cancer module, and the American Urological Association symptom index. Postimplant dosimetry was based on registered T1 spin echo transversal, T2 turbo spin echo transversal, and T2 turbo spin echo sagittal MR images and CT images taken 4 weeks after implantation of the iodine-125 seeds. Calculated parameters were prostate volume, prostate volume receiving 100% (V100) and 150% (V150) dose, dose to 90% of the prostate volume (D90), maximum dose in 1-, 2-, and 5-cm3 rectum volume, distance between prostate and anterior rectum wall, and the maximum dose in 1%, 2%, and 5% urethra volume. Analysis of variance for repeated measures was used for comparison of the means of all variables in the different questionnaires. Linear regression analysis (stepwise) was used to investigate the correlations between QoL parameters and dosimetry parameters. On average, only the QoL at 4 weeks after implant was significantly different from (worse than) the QoL at the other time points. Regression analysis showed a significant correlation between changes in bowel problems and the maximum dose in 2-cm3 rectum volume, between changes in urinary symptoms and prostate volume, and between changes in urinary problems and the D90 value of the prostate. The QoL for patients with permanent prostate implants was worse in the first months after treatment but returned to baseline values 1 year after implant. Significant correlations were found between dose distribution and QoL.

Quality assurance methods for the first Radiation Therapy Oncology Group permanent prostate implant protocol

Purpose To report the quality assurance methodology used by the Radiation Therapy Oncology Group in the first cooperative group, multi-institution Phase II trial of transrectal ultrasound guided permanent radioactive implantation of the prostate for definitive treatment of localized adenocarcinoma of the prostate. Methods and materials Participating institutions were credentialed to participate in this protocol, Radiation Therapy Oncology Group 98-05. International Commission on Radiation Units and Measurements (ICRU) Report 58 was used as the basis for definition of terms. The AAPM's dosimetric prerequisites for low energy interstitial brachytherapy sources were adopted. A nondigital approach to central review was used. The implant dosimetry was recalculated based upon centrally reviewed target volumes by both a radiation oncologist and a diagnostic radiologist. Results There are differences in the definition of the postimplant prostate between the participating institution, the central review radiation oncologist, and the central review diagnostic radiologist. Thus, there are differences in dose/volume parameters. Six of the 95 patients reviewed did not meet the per protocol criteria based upon information supplied by the participating institution. This increased to 18 cases when using the postimplant target volume defined by the central oncologist and to 23 cases when defined by the radiologist. Conclusions This work indicated that there is a need for a central review process of dose–volume analysis within the cooperative group setting. It is indicated that a digital approach to centralized review, which has now been developed, would result in a higher quality and easier review.

SU‐FF‐T‐356: Permanent Prostate Implants: Dose to Critical Structures Inferior to the Prostate

The basic goal of any radiation therapy is to maximize the dose to the tumor while minimizing dose to normal structure. With permanent prostate implants, treatment plans are developed to spare the urethra and the rectum. Post‐implant evaluation shows that the actual implant does not mimic the plan primarily due to prostate swelling and source position shift either at the time of deposition or post implant. Dose indices have been developed to evaluate dose coverage to the implant. 90% prescription to the 100% of the prostate (V100) is considered an excellent implant. A good execution of the implant plan will still maintain a cooler urethra and low dose to the rectum. It is common to see under‐dose in the base region of the prostate and seeds below the apex of the prostate. Sources below the apex of the prostate result in dose to the external sphincter, corpus cavernosum and internal pudendal artery. At our institution, we routinely obtain an MR for anatomic delineation and a CT for source localization 2 weeks after the implant. The datasets are registered based on mutual information techniques and dose to the normal tissue are reported. Fifteen patient entered in this study received a permanent implant to 145 Gy using I125 sources. The average volume of the MR prostate was 50.7cc. The average V100 was 90.5%. The average max dose to the right and left corpus cavernosum was 26.1(10.6) Gy and 28.1(12.4) Gy, respectively. The average max dose to the right and left pudendal arteries was 39.7(25.2) and 40.9(18.5) Gy, respectively. The average dose to 90% of the external sphincter was 132.1(44.9) Gy. With sufficient follow‐up it is possible to correlate the dose to the vascular structures and their effect on erectile function, and dose to the external sphincter and the effect on urinary function.

SU‐FF‐T‐263: Imaging with Brachytherapy Sources

Purpose: To demonstrate the concept of 2D projection and 3D volumetric imaging using brachytherapy treatment sources in patient prior to or during treatment. Method and Materials: As shown Figure 1, an Ir‐192 HDR catheter is placed at 15 cm depth (a reasonable value for pelvic site) in a solid water phantom. XV films are placed on top of the phantom to capture 2D projection images. Vertebra‐like structures serving as anatomical landmarks are placed at mid distance between the catheter and film. Results: The structures are clearly shown on the projection film with a dwell time of 600 seconds. Projection image acquisition time on the order of seconds or less is achievable with more sensitive (100 times more) detectors such as silicone flat panels and detectors used in SPECT cameras. The projection of the landmark coincides with the reference mark when the source is at the correct dwell position and is off the mark when the HDR source is away from the correct dwell position, as shown in Figure 1b and 1c. Thus a “port film” approach can be developed to verify the source position prior to treatment. With the possibility of verifying one dwell position against its reference mark, all other dwell positions can be verified against its own the reference mark. This provides a way of dynamically tracking the dwell positions of a multiple dwell position treatment plan. With projections taken at multiple angles with sensitive detectors at a fraction of a typical therapeutic dwell time, it will be possible and useful to obtain volume images of the treatment sources superimposed on anatomy, using tomographic (CT, SPECT, tomosynthesis) reconstruction methods. Conclusion: Three dimensional volume imaging with a HDR treatment source has been demonstrated. The concept applies to other brachytherapy modalities, e.g., SPECT for permanent prostate implants, LDRs.

PSA bounce after permanent implant prostate brachytherapy may mimic a biochemical failure: A study of 295 patients with a minimum 3-year followup

Purpose To assess the frequency and features of the PSA bounce phenomenon in a series of patients treated with permanent implant brachytherapy for prostate cancer, and to evaluate the percentage of cases in which this bounce could have mimicked a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology consensus criteria. Methods and materials From January 1999 to December 2001, 295 patients were treated with a permanent prostate implantation (real-time technique, with free 125I seeds) by the Paris Institut Curie/Hospital Cochin/Hospital Necker Paris group. Duration of followup is 40.3 months (9–66 months). PSA level was reported at intervals not exceeding 6 months. Bounce was defined by temporary elevation in PSA level, followed by a spontaneous decrease. Results In our series, 161 patients (55%) showed a transitory PSA increase (bounce) of at least 0.1 ng/mL; 145 patients (49%) a bounce of 0.2 ng/mL; 93 patients (32%) a bounce of 0.4 ng/mL; and 43 patients (15%) a bounce of at least 1 ng/mL. Mean PSA bounce was 0.8 ng/mL (0.1–4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of total) presented three successive PSA increases, and therefore were to be considered as experiencing a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria. Among those 32 patients, 18 (56%) subsequently showed, without any treatment, a complete normalization of their PSA. In multivariate analysis, age <70 ( p < 0.0001) and D90 > 200 Gy ( p < 0.003) were identified as independent factors for a PSA bounce of at least 0.4 ng/mL. Conclusions The observed rate of 32% of patients showing a PSA bounce of at least 0.4 ng/mL in our series is in good agreement with what has been previously reported in the literature. Among 32 patients fulfilling the classical ASTRO criteria for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, questioning the ASTRO consensus for the biochemical followup of patients undergoing permanent implant prostate brachytherapy.

Three-dimensional conformal external beam radiotherapy compared with permanent prostate implantation in low-risk prostate cancer based on endorectal magnetic resonance spectroscopy imaging and prostate-specific antigen level

To evaluate the metabolic response by comparing the time to resolution of spectroscopic abnormalities (TRSA) and the time to prostate-specific antigen level in low-risk prostate cancer patients after treatment with three-dimensional conformal external beam radiotherapy (3D-CRT) compared with permanent prostate implantation (PPI). Recent studies have suggested that the treatment of low-risk prostate cancer yields similar results for patients treated with 3D-CRT or PPI. A total of 50 patients, 25 in each group, who had been treated with 3D-CRT or PPI, had undergone endorectal magnetic resonance spectroscopy imaging before and/or at varying times after therapy. The 3D-CRT patients had received radiation doses of > or =72 Gy compared with 144 Gy for the PPI patients. The spectra from all usable voxels were examined for detectable levels of metabolic signal, and the percentages of atrophic and cancerous voxels were tabulated. The median time to resolution of the spectroscopic abnormalities was 32.2 and 24.8 months and the time to the nadir prostate-specific antigen level was 52.4 and 38.0 months for the 3D-CRT and PPI patients, respectively. Of the 3D-CRT patients, 92% achieved negative endorectal magnetic resonance spectroscopy imaging findings, with 40% having complete metabolic atrophy. All 25 PPI patients had negative endorectal magnetic resonance spectroscopy imaging findings, with 60% achieving complete metabolic atrophy. The results of this study suggest that metabolic and biochemical responses of the prostate are more pronounced after PPI. Our results have not proved PPI is more effective at curing prostate cancer, but they have demonstrated that it may be more effective at destroying prostate metabolism.

Evaluation of an automated seed loader for seed calibration in prostate brachytherapy

Automated seed loaders for permanent prostate implants are now commercially available. Besides improved radiation safety, these systems offer seed assay capability and ease of needle loading, making preplanned as well as intra‐operative implant procedures more time‐efficient. The Isoloader (Mentor Corp., CA) uses individual I125 seeds (SL‐125 ProstaSeed) loaded in up to 199 chambers inside a shielded cartridge. The unit performs seed counting and calibration using a built‐in solid‐state detector. In order to evaluate the reproducibility and accuracy of the calibration process, two test cartridges were measured with the Isoloader itself and compared with a well‐type ionization chamber (HDR‐1000Plus, Standard Imaging).The air kerma strength measurements for all seeds using the Isoloader had a standard deviation of about 2.7%. For the eight seeds assayed more intensively using both the Isoloader and well chamber, the standard deviations of the measurements for each seed were in the range of 0.8% to 2.8% and 0.6% to 1.3%, respectively. The variation in the Isoloader calibration is attributed to small detector solid angle and bead geometry within seed capsules (verified by radiographs). The reproducibility of the air kerma strength measured by the Isoloader was comparable to that from the well chamber and was clinically acceptable. Seed strength measured with the Isoloader was on average 1%~2% larger than that measured with the well chamber, indicating that the accuracy of the Isoloader was clinically acceptable.PACS numbers: 87.53.Jw, 87.53.Xd, 87.56.Fc

Prostatic edema in permanent prostate implants: Dynamical dosimetry taking volume changes into account

The purpose of this study is to determine the impact of edema on the dose delivered to the target volume. An evaluation of the edema characteristics was first made, and then a dynamical dosimetry algorithm was developed and used to compare its results to a standard clinical (static) dosimetry. Source positions and prostate contours extracted from 66 clinical cases on images taken at different points in time (planning, implant day, post-implant evaluation) were used, via the mean interseed distance, to characterize edema [initial increase (deltar0), half-life (tau)]. An algorithm was developed to take into account the edema by summing a time series of dose-volume histograms (DVHs) with a weight based on the fraction of the dose delivered during the time interval considered. The algorithm was then used to evaluate the impact of edema on the dosimetry of permanent implants by comparing its results to those of a standard clinical dosimetry. The volumetric study yielded results as follows: the initial prostate volume increase was found to be 1.58 (ranging from 1.15 to 2.48) and the edema half-life, approximately 30 days (range: 3 to 170 days). The dosimetric differences in D90 observed between the dynamic dosimetry and the clinical one for a single case were up to 15 Gy and depended on the edema half-life and the initial volume increase. The average edema half-life, 30 days, is about 3 times longer than the previously reported 9 days. Dosimetric differences up to 10% of the prescription dose are observed, which can lead to differences in the quality assertion of an implant. The study of individual patient edema resorption with time might be necessary to extract meaningful clinical correlation or biological parameters in permanent implants.

Impact of interseed attenuation and tissue composition for permanent prostate implants

The purpose is to evaluate the impact of interseed attenuation and prostate composition for prostate treatment plans with 125I permanent seed implants using the Monte Carlo (MC) method. The effect of seed density (number of seeds per prostate unit volume) is specifically investigated. The study focuses on treatment plans that were generated for clinical cases. For each plan, four different dose calculation techniques are compared: TG-43 based calculation, superposition MC, full MC with water prostate, and full MC with realistic prostate tissue. The prostate tissue description is from the ICRP report 23 (W. S. Snyer, M. J. Cook, E. S. Nasset, L. R. Karkhausen, G. P. Howells, and I. H. Tipton, "Report of the task group on reference man," Technical Report 23, International Commission on Radiological Protection, 1974). According to the comparisons, the seed density has an influence on interseed attenuation. A plan with a typical low seed density (42 0.6 mCi seeds in a 26 cm3 prostate) suffers a 1.2% drop in the CTV D90 value due to interseed attenuation. A drop of 3.0% is calculated for a higher seed density (75 0.3 mCi seeds, same prostate). The influence of the prostate composition is similar for all seed densities and prostate sizes. The difference between MC simulations in water and MC simulations in prostate tissue is between 4.4% and 4.8% for the D90 parameter. Overall, the effect on D90 is ranging from 5.8% to 12.8% when comparing clinically approved TG-43 and MC simulations in prostate tissue. The impact varies from one patient to the other and depends on the prostate size and the number of seeds. This effect can reach a significant level when reporting correlations between clinical effect and deposited dose.

Comparison of day 0 and day 14 dosimetry for permanent prostate implants using stranded seeds

To determine, using MRI-based dosimetry (Day 0 and Day 14), whether clinically significant changes in the dose to the prostate and critical adjacent structures occur between Day 0 and 14, and to determine to what degree any changes in dosimetry are due to swelling or its resolution. A total of 28 patients with a permanent prostate implant using 125I rapid strands were evaluated at Days 0 and 14 by CT/MRI fusion. The minimal dose received by 90% of the target volume (prostate D90), percentage of volume receiving 100% of prescribed minimal peripheral dose (prostate V100), external sphincter D90, and 4-cm3 rectal volume dose were calculated. An acceptable prostate D90 was defined as D90 >90% of prescription dose. Prostate volume changes were calculated and correlated with any dosimetry change. A paradoxic dosimetric result was defined as an improvement in D90, despite increased swelling; a decrease in D90, despite decreased swelling; or a large change in D90 (>30 Gy) in the absence of swelling. The D90 changed in 27 of 28 patients between Days 0 and 14. No relationship was found between a change in prostate volume and the change in D90 (R2 = 0.01). A paradoxic dosimetric result was noted in 11 of 28 patients. The rectal dose increased in 23 of 28 patients, with a >30-Gy change in 6. The external sphincter D90 increased in 19 of 28, with a >50-Gy increase in 6. The dose to the prostate changed between Days 0 and 14 in most patients, resulting in a change in clinical status (acceptable or unacceptable) in 12 of 28 patients. Profound increases in normal tissue doses may make dose and toxicity correlations using Day 0 dosimetry difficult. No relationship was found between the prostate volume change and D90 change, and, in 11 patients, a paradoxic dosimetric result was noted. A differential z-axis shift of stranded seeds vs. prostate had a greater impact on final dosimetry and dose to critical adjacent tissues than did prostate swelling. These findings challenge the model that swelling is the principal cause of dosimetric changes after implantation. Stranded seeds may have contributed to this outcome. On the basis of these findings, a change in technique to avoid placement of stranded seeds inferior to the prostate apex has been adopted. These results may not apply to implants using single seeds within the prostate.

Magnetic Resonance Spectroscopy Imaging and PSA Responses Following Three-Dimensional Conformal External Beam Radiotherapy (3DCRT) or 3DCRT plus Permanent Prostate Implant (PPI) for Intermediate Risk Prostate Cancer

Magnetic Resonance Spectroscopy Imaging and PSA Responses Following Three-Dimensional Conformal External Beam Radiotherapy (3DCRT) or 3DCRT plus Permanent Prostate Implant (PPI) for Intermediate Risk Prostate Cancer

Are Biochemical Control (bNED) Rates Following Permanent Prostate Implants (PPI) Consistent with Findings on Endorectal Magnetic Resonance Spectroscopy Imaging (eMRSI)?

Are Biochemical Control (bNED) Rates Following Permanent Prostate Implants (PPI) Consistent with Findings on Endorectal Magnetic Resonance Spectroscopy Imaging (eMRSI)?

Po‐Poster ‐ 26: Investigation of normalized mutual information for co‐registration of CT — MR images of permanent prostate implants

Post‐implant dosimetric evaluation is the standard contemporary method for assessing permanent prostate implant quality and determining the dose received by the prostate and organs at risk over the course of treatment. In current practice evaluation is performed using a CT image set typically acquired one month after the implant. However, due to poor visualization of prostate contours on the CT images, the evaluation can be difficult and is only approximate. MRI allows a better appreciation of prostate contours, but the visibility of the ensemble of the seeds is insufficient to allow its use as the only means of evaluating the treatment. Image registration of CT and MR image sets can combine the benefits of both imaging modalities and provide the means for sufficiently accurate dosimetric analysis. Mutual information is an efficient registration technique that can be used to fuse selected volumes of interest such as the prostate and neighbouring tissues. In our study we investigate optimization of registration search parameters, such as threshold level, translation and rotation angle ranges, and volume boundaries for fusing CT — MR images of a tissue equivalent prostate phantom implanted with inactive seeds, simulated image data, and clinical data sets. The results obtained so far are encouraging and suggest that mutual information‐based registration may eventually enable automatic fusion of clinical CT and MR images for prostate implant post‐dosimetry.

Quality of life of patients after permanent prostate brachytherapy in relation to dosimetry

To investigate changes in quality of life (QoL) after permanent prostate brachytherapy and to correlate these changes with postimplant dosimetry based on magnetic resonance (MR) images. For this study, 127 patients with low-stage prostate cancer and treated with brachytherapy received a QoL questionnaire at five time points: before treatment and at 4 weeks, 6 months, 1 year, and 2 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer (EORTC) core questionnaire, the tumor-specific EORTC prostate cancer module, and the American Urological Association symptom index. Postimplant dosimetry was based on registered T1 spin echo transversal, T2 turbo spin echo transversal, and T2 turbo spin echo sagittal MR images and CT images taken 4 weeks after implantation of the iodine-125 seeds. Calculated parameters were prostate volume, prostate volume receiving 100% (V100) and 150% (V150) dose, dose to 90% of the prostate volume (D90), maximum dose in 1-, 2-, and 5-cm3 rectum volume, distance between prostate and anterior rectum wall, and the maximum dose in 1%, 2%, and 5% urethra volume. Analysis of variance for repeated measures was used for comparison of the means of all variables in the different questionnaires. Linear regression analysis (stepwise) was used to investigate the correlations between QoL parameters and dosimetry parameters. On average, only the QoL at 4 weeks after implant was significantly different from (worse than) the QoL at the other time points. Regression analysis showed a significant correlation between changes in bowel problems and the maximum dose in 2-cm3 rectum volume, between changes in urinary symptoms and prostate volume, and between changes in urinary problems and the D90 value of the prostate. The QoL for patients with permanent prostate implants was worse in the first months after treatment but returned to baseline values 1 year after implant. Significant correlations were found between dose distribution and QoL.

SU‐FF‐T‐22: Application of Neural Network Algorithm for Treatment Planning Verification of Permanent Prostate Implants

Purpose: The objective of this project is the evaluation of a software brachytherapy nomogram equivalent. This program was designed to predict the required air kerma strength and source count for implants based on site dimensions and volumes. Method and Materials: The nomogram equivalent is based on a three‐layer feed‐forward neural network (NN). The software consists of two separate programs. One program is used for training the NN and the second program is executed for realizing the nomogram equivalent. The NN was trained using site dimensions, volumes and implanted air kerma strengths for 117 prostate cases. The network was then tested on 30 cases not included in the training set. The results of the NN calculations were also compared with the Anderson nomogram predictions. Results: The accuracy of the NN nomogram equivalent is a function of the quality and quantity of training data, the number of iterations set to obtain the desired results, and a consistent source loading methodology. The NN predictions of the total activity and source count are in good agreement (within 11%) with the computer optimized preplanning results for all but two cases. Upon review, significant treatment volume underdosing was observed for these two cases. The Anderson nomogram prediction of the planned total activity was within 13% for all but the two outlier cases. Conclusion: The NN based program implemented in the clinic can be an easy, fast, and accurate tool for performing independent verification of interstitial prostate implants. The NN is field‐customizable, a capability not possible with a standard nomogram.

MO-E-T-618-01: An Integrated CT-Based Monte Carlo Dose-Evaluation System for Brachytherapy and Its Application to Permanent Prostate Implant Postprocedure Dosimetric Analysis

Purpose: To develop a novel integrated CT-based Monte Carlo (MC) dose-evaluation system and use it to investigate the effect of tissue heterogeneities and interseed attenuation on brachytherapy dose distributions. Method and Materials: A MC photon-transport (MCPT) brachytherapy dose-calculation engine, PTRAN_CT, which uses x-ray CT to estimate tissue cross-sections, is developed based on PTRAN_CCG version 7.44. PTRAN_CT uses fast ray tracing that combines patient anatomy modeling via 3D voxel arrays with modeling of sources and applicators via a general combinatorial geometry code. A generalized phase-space source is used for further increasing efficiency. PTRAN_CT uses cross-section data derived from a single-energy CT image. PTRAN_CT was incorporated into an integrated system for performing postimplant dosimetric analysis of permanent prostate implants. A clinical implant consisting of 78 Model-6711 I-125 seeds was investigated to quantify interseed and tissue heterogeneity effects. Three scenarios were simulated a) comprehensive MC simulation including tissue heterogeneities and complete seed geometry b) complete seed geometry in homogeneous water and c) homogeneous water using 2D TG-43 source superposition. Results: Compared to case b), tissue heterogeneities (case a)) reduce doses by 5.8% on average in the target volume, after excluding artifacts from CT data. Interseed effects (case b) vs c)), reduce doses by 3% on average. The seed streaking artifact in CT data can affect MC result as large as 6%. The efficiency of PTRAN_CT relative to the predecessor code PTRAN_CCG is increased by factors of two and five, respectively, with and without enabling the phase-space option. In case b), PTRAN_CT yields the same dose distribution as benchmarked PTRAN_744. Conclusion: A novel post-implant dose evaluation system, based upon an accelerated CT-based Monte Carlo brachytherapy dose-calculation engine, has been developed and its accuracy and efficiency demonstrated. Preliminary results suggest that tissue heterogeneity effects can be incorporated into the clinical planning process.

67 Class solution for inversely planned permanent prostate implants to mimic an experienced dosimetrist for pre and live treatment planning

67 Class solution for inversely planned permanent prostate implants to mimic an experienced dosimetrist for pre and live treatment planning

87 Objective comparison of RAPID strand and free selectSeeds loading for permanent prostate implants using an inverse planning approach

87 Objective comparison of RAPID strand and free selectSeeds loading for permanent prostate implants using an inverse planning approach

58 Comparison of prostate volumes delineated on pre-implant MRI, pre-implant US and intra-operative US images for planning of permanent prostate implants

58 Comparison of prostate volumes delineated on pre-implant MRI, pre-implant US and intra-operative US images for planning of permanent prostate implants

90 Fusion of pre-implant MRI and intra-operative US images for planning of permanent prostate implants

90 Fusion of pre-implant MRI and intra-operative US images for planning of permanent prostate implants