Peter L. Roberson

Source placement error for permanent implant of the prostate

The performance of ultrasound (US) and fluoroscopic-guided permanent 125I source implant of the prostate using CT identification of the source positions has been evaluated. Marker seeds were implanted during the planning study to assist in the alignment of the US and CT prostate volumes for treatment planning and to guide the placement of needles. The relative positions of the needles and marker seeds were checked by fluoroscopy. A postimplant CT study was used to input the radioactive source positions and to register the sources relative to the preimplant CT and US prostate volumes and the planned source distribution. Source placement errors observed were categorized as: (1) source-to-source spacing differences; (2) needle placement error, both depth and position; and (3) seed splaying, particularly near the prostate periphery. Errors due to source splaying and spacing were in part attributed to prostate motion. Later refinements included fixed-spaced string sources, for which placement errors were smaller than for unattached sources. However, source placement errors due to needle placement error and prostate motion remained unchanged.

MIRD Pamphlet No. 23: Quantitative SPECT for Patient-Specific 3-Dimensional Dosimetry in Internal Radionuclide Therapy

In internal radionuclide therapy, a growing interest in voxel-level estimates of tissue-absorbed dose has been driven by the desire to report radiobiologic quantities that account for the biologic consequences of both spatial and temporal nonuniformities in these dose estimates. This report presents an overview of 3-dimensional SPECT methods and requirements for internal dosimetry at both regional and voxel levels. Combined SPECT/CT image-based methods are emphasized, because the CT-derived anatomic information allows one to address multiple technical factors that affect SPECT quantification while facilitating the patient-specific voxel-level dosimetry calculation itself. SPECT imaging and reconstruction techniques for quantification in radionuclide therapy are not necessarily the same as those designed to optimize diagnostic imaging quality. The current overview is intended as an introduction to an upcoming series of MIRD pamphlets with detailed radionuclide-specific recommendations intended to provide best-practice SPECT quantification–based guidance for radionuclide dosimetry.

Impact of differences in ultrasound and computed tomography volumes on treatment planning of permanent prostate implants

PURPOSE Both ultrasound (US) and computerized tomography (CT) images have been used in the planning of prostate interstitial therapy. Ultrasound images more clearly define the apex and capsule of the prostate, while CT images define seed positions for postimplant dosimetry. Proper registration of the US volume with the CT volume is critical to the assessment of dosimetry. We therefore compared US and CT prostate volumes to determine if differences were significant. METHODS AND MATERIALS Ten consecutive patients entered in an interstitial implant program were studied by pretreatment US. In addition, pretreatment CT scans were obtained and three physicians independently outlined the dimensions of the prostate on these images. The patients subsequently underwent placement of radioactive 125I or 103Pd. Postimplant CT images were obtained the next day and the postimplant prostate volumes were outlined by the same three physicians. Seven of 10 patients underwent late CT scans 9-14 months postimplant for comparison of preimplant and immediate postimplant CT studies. RESULTS There were differences between US and CT volumes. Although the physician-to-physician variation was significant, the trends were consistent, with US prostate volume typically smaller (47%) than the preimplant CT volume and markedly smaller (120%) than the postimplant CT volume. Prostate volumes derived from late CT images did not consistently return to preimplant levels. CONCLUSIONS Significant differences in volume of the prostate structure were found between US and CT images. The data suggests that: (a) Implants planned on CT tend to overestimate the size of the prostate and may lead to unnecessary implantation of the urogenital diaphragm and penile urethra. (b) Registration of initial US and postimplant CT prostate volumes required for accurate dosimetry is difficult due to the increased volume of prostate secondary to trauma. (c) Further study to determine the optimal time for the postimplant CT is necessary.

Prostate position late in the course of external beam therapy: patterns and predictors

PURPOSE To examine prostate and seminal vesicles position late in the course of radiation therapy and to determine the effect and predictive value of the bladder and rectum on prostate and seminal vesicles positioning. METHODS AND MATERIALS Twenty-four patients with localized prostate cancer underwent a computerized tomography scan (CT1) before the start of radiation therapy. After 4-5 weeks of radiation therapy, a second CT scan (CT2) was obtained. All patients were scanned in the supine treatment position with instructions to maintain a full bladder. The prostate, seminal vesicles, bladder, and rectum were contoured. CT2 was aligned via fixed bony anatomy to CT1. The geometrical center and volume of each structure were obtained and directly compared. RESULTS The prostate shifted along a diagonal axis extending from an anterior-superior position to a posterior-inferior position. The dominant shift was to a more posterior-inferior position. On average, bladder and rectal volumes decreased to 51% (+/-29%) and 82% (+/-45%) of their pretreatment values, respectively. Multiple regression analysis (MRA) revealed that bladder movement and volume change and upper rectum movement were independently associated with prostate motion (p = 0.016, p = 0. 003, and p = 0.052 respectively). CONCLUSION Patients are often instructed to maintain a full bladder during a course of external beam radiation therapy, in the hopes of decreasing bladder and small bowel toxicity. However, our study shows that large bladder volumes late in therapy are strongly associated with posterior prostate displacement. This prostate displacement may result in marginal miss.

Impact of ultrasound and computed tomography prostate volume registration on evaluation of permanent prostate implants

PURPOSE Ultrasound (US)-guided permanent prostate implants typically use US prostate volumes to plan the implant procedure and CT prostate volumes for 3D dosimetric evaluation of the implant. Such a protocol requires that CT and US prostate volumes be registered. We have studied the impact of prostate volume registration on postimplant dosimetry for patients with low-grade prostate cancer treated with combined US and fluoroscopic-guided permanent implants. METHODS AND MATERIALS A US image set was obtained with the patient in the lithotomy position to delineate the prostate volume that was subsequently used for treatment planning. Each plan was customized and optimized to ensure complete coverage of the US prostate volume. After implant, a CT scan was obtained for postimplant dosimetry with the patient lying supine. Sources were localized on CT by interactively creating orthogonal images of small cubes, whose dimensions were slightly larger than the source, to assure unique identification of each seed. Ultrasound and CT 3D surfaces were registered using either (a) the rectal surface and base of the prostate, or (b) the Foley balloon and urethra as the alignment reference. A dose distribution was assigned to the US prostate volume based on the CT source distribution, and the dose-volume histogram (DVH) was calculated. RESULT Prostate volumes drawn from US images differ from those drawn from CT images with the CT volumes being typically larger than the US volumes. Urethral registration of the prostate volume based on aligning the prostatic urethra generates a dose distribution that best follows the preimplant plan and is geometrically the preferable choice for dosimetry. CONCLUSION The dose distribution and the DVH for the US prostate is sensitive to the mode of registration limiting the ability to determine if acceptable dose coverage has been achieved.

131I-Tositumomab Radioimmunotherapy: Initial Tumor Dose–Response Results Using 3-Dimensional Dosimetry Including Radiobiologic Modeling

For optimal treatment planning in radionuclide therapy, robust tumor dose–response correlations must be established. Here, fully 3-dimensional (3D) dosimetry was performed coupling SPECT/CT at multiple time points with Monte Carlo–based voxel-by-voxel dosimetry to examine such correlations. Methods: Twenty patients undergoing 131I-tositumomab for the treatment of refractory B-cell lymphoma volunteered for the study. Sixty tumors were imaged. Activity quantification and dosimetry were performed using previously developed 3D algorithms for SPECT reconstruction and absorbed dose estimation. Tumors were outlined on CT at multiple time points to obtain absorbed dose distributions in the presence of tumor deformation and regression. Equivalent uniform dose (EUD) was calculated to assess the biologic effects of the nonuniform absorbed dose, including the cold antibody effect. Response for correlation analysis was determined on the basis of the percentage reduction in the product of the largest perpendicular tumor diameters on CT at 2 mo. Overall response classification (as complete response, partial response, stable disease, or progressive disease) used for prediction analysis was based on criteria that included findings on PET. Results: Of the evaluated tumor-absorbed dose summary measures (mean absorbed dose, EUD, and other measures from dose-volume histogram analysis), a statistically significant correlation with response was seen only with EUD (r = 0.36 and P = 0.006 at the individual tumor level; r = 0.46 and P = 0.048 at the patient level). The median value of mean absorbed dose for stable disease, partial response, and complete response patients was 196, 346, and 342 cGy, respectively, whereas the median value of EUD for each of these categories was 170, 363, and 406 cGy, respectively. At a threshold of 200 cGy, both mean absorbed dose and EUD had a positive predictive value for responders (partial response + complete response) of 0.875 (14/16) and a negative predictive value of 1.0 (3/3). Conclusion: Improved dose–response correlations were demonstrated when EUD incorporating the cold antibody effect was used instead of the conventionally used mean tumor-absorbed dose. This work demonstrates the importance of 3D calculation and radiobiologic modeling when estimating absorbed dose for correlation with outcome.

Use and uncertainties of mutual information for computed tomography/magnetic resonance (CT/MR) registration post permanent implant of the prostate

Post-implant dosimetric analysis for permanent implant of the prostate benefits from the use of a computed tomography (CT) dataset for optimal identification of the radioactive source (seed) positions and a magnetic resonance (MR) dataset for optimal description of the target and normal tissue volumes. The CT/MR registration process should be fast and sufficiently accurate to yield a reliable dosimetric analysis. Since critical normal tissues typically reside in dose gradient regions, small shifts in the dose distribution could impact the prediction of complication or complication severity. Standard procedures include the use of the seed distribution as fiducial markers (seed match), a time consuming process that relies on the proper identification of signals due to the same seed on both datasets. Mutual information (MI) is more efficient because it uses image data requiring minimal preparation effort. A comparison of MI registration and seed-match registration was performed for twelve patients. MI was applied to a volume limited to the prostate and surrounding structures, excluding most of the pelvic bone structures (margins around the prostate gland were approximately 2 cm right-left, approximately 1 cm anterior-posterior, and approximately 2 cm superior-inferior). Seeds were identified on a 2 mm slice CT dataset using an automatic seed identification procedure on reconstructed three-dimensional data. Seed positions on the 3 mm slice thickness T2 MR data set were identified using a point-and-click method on each image. Seed images were identified on more than one MR slice, and the results used to determine average seed coordinates for MR images and matched seed pairs between CT and MR images. On average, 42% (19%-64%) of the seeds (19-54 seeds) were identified and matched to their CT counterparts. A least-squares method applied to the CT and MR seed coordinates was used to produce the optimum seed-match registration. MI registration and seed match registration angle differences averaged 0.5 degrees, which was not significantly different from zero. Translation differences averaged 0.6 (1.2 standard deviation) mm right-left, -0.5(1.5) mm posterior-anterior, and -1.2(2.0) mm inferior-superior. Registration error estimates were approximately 2 mm for both the MI and seed-match methods. The observed standard deviations in the offset values were consistent with propagation of error. Registration methods as applied here using mutual information and seed matching are consistent, except for a small systematic difference in the inferior-superior axis for a minority of cases (approximately 15%). Cases registered with mutual information and with bony anatomy misregistration of greater than approximately 5 mm should be evaluated for rescan or seed-match registration. The improvement in efficiency of use for the MI registration method is substantial, approximately 30 min compared to several hours using seed match registration.

Comparison of MRI pulse sequences in defining prostate volume after permanent implantation

PURPOSE To determine the relative value of three MRI pulse sequences in defining the prostate volume after permanent implantation. METHODS AND MATERIALS A total of 45 patients who received a permanent 125I implant were studied. Two weeks after implantation, an axial CT scan (2 mm thickness) and T1-weighted, T1-weighted fat saturation, and T2-weighted axial MRI (3-mm) studies were obtained. The prostate volumes were compared with the initial ultrasound planning volumes, and subsequently the CT, T1-weighted, and T1-weighted fat saturation MRI volumes were compared with the T2-weighted volumes. Discrepancies in volume were evaluated by visual inspection of the registered axial images and the registration of axial volumes on the sagittal T2-weighted volumes. In a limited set of patients, pre- and postimplant CT and T2-weighted MRI studies were available for comparison to determine whether prostate volume changes after implant were dependent on the imaging modality. RESULTS T1-weighted and T1-weighted fat saturation MRI and CT prostate volumes were consistently larger than the T2-weighted MRI prostate volumes, with a volume on average 1.33 (SD 0.24) times the T2-weighted volume. This discrepancy was due to the superiority of T2-weighted MRI for prostate definition at the following critical interfaces: membranous urethra, apex, and anterior base-bladder and posterior base-seminal vesicle interfaces. The differences in prostate definition in the anterior base region suggest that the commonly reported underdose may be due to overestimation of the prostate in this region by CT. The consistent difference in volumes suggests that the degree of swelling observed after implantation is in part a function of the imaging modality. In patients with pre- and postimplant CT and T2-weighted MRI images, swelling on the T2-weighted images was 1.1 times baseline and on CT was 1.3 times baseline, confirming the imaging modality dependence of prostate swelling. CONCLUSION Postimplant T2-weighted MRI images provided superior prostate definition in all critical regions of the prostate compared with CT and the other MRI sequences tested. In addition to defining an optimal technique, these findings call two prior observations into question. Under dosing at the anterior base region may be overestimated because of poor definition of the prostate-bladder muscle interface. The swelling observed after implantation was lower on T2-weighted images as well, suggesting that a fraction of postimplant swelling is a function of the imaging modality. These findings have implications for preimplant planning and postimplant evaluation. As implant planning techniques become more conformal, and registration methods become more efficient, T2-weighted MRI after implantation will improve the accuracy of postimplant dosimetry.

The effect of patient position and treatment technique in conformal treatment of prostate cancer

PURPOSE The relative value of prone versus supine positioning and axial versus nonaxial beam arrangements in the treatment of prostate cancer remains controversial. Two critical issues in comparing techniques are: 1) dose to critical normal tissues, and 2) prostate stabilization. METHODS AND MATERIALS Ten patients underwent pretreatment CT scans in one supine and two prone positions (flat and angled). To evaluate normal tissue exposure, prostate/seminal vesicle volumes or prostate volumes were expanded 8 mm and covered by the 95% isodose surface by both 6-field axial and 4-field nonaxial techniques. A total of 280 dose-volume histograms (DVHs) were analyzed to evaluate dose to rectal wall and bladder relative to patient position and beam arrangement. A CT scan was repeated in each patient after 5 weeks of treatment. Prostate motion was assessed by comparing early to late scans by three methods: 1) center of mass shift, 2) superior pubic symphysis to anterior prostate distance, and 3) deviation of the posterior surface of the prostate. RESULTS For prostate (P) or prostate/seminal vesicle (P/SV) treatments, prone flat was advantageous or equivalent to other positions with regard to rectal sparing. The mechanism of rectal sparing in the prone position may be related to a paradoxical retraction of the rectum against the sacrum, away from the P/SV. Although there was no clear overall preference for beam arrangement, substantial improvements in rectal sparing could be realized for individual patients. In this limited number of patients, there was no convincing evidence prostate position was stabilized by prone relative to supine position. CONCLUSIONS Prone flat positioning was advantageous over other positions and beam arrangements in rectal sparing. This study suggests that patient position is a more critical a factor in conformal therapy than beam arrangement, and may improve the safety of dose escalation.

Assessment of skin dose for breast chest wall radiotherapy as a function of bolus material

Skin dose assessment for chest wall radiotherapy is important to ensure sufficient dose to the surface target volume without excessive skin reaction. This study quantified changes to the surface doses as a function of bolus material for conventional and intensity modulated radiation therapy (IMRT) tangential fields. Three types of bolus materials (2 mm solid, 2 mm fine mesh and 3.2 mm large mesh Aquaplast) were compared with Superflab. Surface dose measurements were performed using an Attix parallel plate chamber in a flat solid water phantom at 0 degrees , 45 degrees and 70 degrees incident angles. Over-response correction factors were applied to the Attix chamber results for different incident angles. Surface dose measurements on an anthropomorphic phantom were done using a thermoluminescent dosimeter extrapolation method. Dose characteristics of Superflab and solid Aquaplast were within 2% of solid water material. No significant differences (within 3%) in the surface dose were found between conventional and IMRT tangential techniques. The bolus effect was large for chest wall tangential radiotherapy, with up to an 82% increase using 2 mm fine mesh Aquaplast. The dosimetric effect of different Aquaplast materials has been quantified in this work. These materials can be used to create a custom bolus with potentially better reproducibility of placement.