Ultrasound-based stereotactic guidance in prostate cancer--quantification of organ motion and set-up errors in external beam radiation therapy.

OBJECTIVE: A mobile transabdominal ultrasound-based targeting system (BAT(R)) has been developed which can stereotactically localize the position of the prostate each treatment day and directly integrate this information into the treatment planning system. Daily target verification facilitates a marked reduction in planning treatment margins by correcting potential organ-motion and set-up errors. Previous studies have been performed to establish the precision of ultrasound localization. This report quantifies the magnitude of the patient isocenter shift parameters encountered during clinical implementation of this system. MATERIAL AND METHODS: After five weeks of conformal external beam radiation therapy, 54 patients underwent a second CT simulation. Prostate-only fields based on this scan were created with no PTV margin beyond the CTV. For each of the final conedown treatments (2-4 fractions), patients underwent ultrasound-based stereotactic prostate localization at the treatment machine. The portable system, which electronically imports the CT simulation target-contour and isocenter information, is situated adjacent to the treatment couch. Transverse and sagittal suprapubic ultrasound images are captured, and the system electronically couples this data to the baseline isocenter. The CT contours are maneuvered in three dimensions by a touch-screen menu to visually overlay the ultrasound images. The system then displays the three-dimensional (3D) couch shifts required to produce field alignment. RESULTS: One hundred and eighty-nine daily ultrasound prostate position shifts were recorded for 54 patients. The isocenter field misalignment between the baseline CT and ultrasound ranged from -26.8 to 33.8 mm in the anterior/posterior (A/P) dimension, -10.2 to 30.9 mm in the lateral dimension, and -24.6 to 9.0 mm in the superior/inferior (S/I) dimension. The corresponding directed average disagreements were -3.0 mm (SD 8.3 mm) A/P, 1.86 mm (SD 5.7 mm) lateral, and -2.6 mm (SD 6.5 mm) S/I. The magnitudes of undirected misalignments were frequently larger than 5 mm (51% of A/P, 31% of lateral, and 35% of superior measurements) and oftentimes larger than 10 mm (21% of A/P, 7% of lateral, and 12% of superior measurements). CONCLUSIONS: Organ motion and set-up uncertainties limit optimization of 3D treatment planning by expanding the width of PTV margins required to ensure target coverage. Transabdominal ultrasound-based stereotactic guidance is a safe and direct method for correcting patient positioning. Our experience with the BAT system in a large cohort of prostate cancer patients revealed that substantial daily isocenter corrections were encountered in a large percentage of cases. This data would suggest that daily clinical isocenter misalignments are greater than would be expected from published data on organ motion and set-up variations encountered in the study setting.

Ultrasound-based stereotactic guidance of precision conformal external beam radiation therapy in clinically localized prostate cancer.

OBJECTIVES: Use of external beam radiation fields that conform to the shape of the target improves biochemical control in prostate cancer by facilitating dose escalation through increased sparing of normal tissue. By correcting potential organ motion and setup errors, ultrasound-directed stereotactic localization is a method that may improve the accuracy and effectiveness of current conformal technology. The purpose of this study was to quantify the precision of the transabdominal ultrasound-based approach using computed tomography (CT) as a standard. METHODS: Thirty-five consecutive men participated in a prospective comparison of daily CT and ultrasound-guided localization at Fox Chase Cancer Center. Daily CT prostate localization was completed before the delivery of each final boost field. In the CT simulation suite, transabdominal ultrasound-based stereotactic localization was also performed. The main outcome measure was a three-dimensional comparison of prostate position as determined by CT versus ultrasound. RESULTS: Sixty-nine daily CT and ultrasound prostate position shifts were recorded for 35 patients. The magnitude of difference between the CT and ultrasound localization ranged from 0 to 7.0 mm in the anterior/posterior, 0 to 6.4 mm in the lateral, and 0 to 6.7 mm in the superior/inferior dimension. The corresponding directed average disagreements were extremely small: anterior/posterior, -0.09 +/- 2.8 mm SD; lateral, -0.16 +/- 2.4 mm SD; and superior/inferior, -0.03 +/- 2.3 mm SD). Analysis of the paired CT-ultrasound shifts revealed a high correlation between the two modalities in all three dimensions (anterior/ posterior r = 0.88; lateral r = 0.91; and superior/inferior r = 0.87). CONCLUSIONS: Ultrasound-directed stereotactic localization is safe and as accurate as CT scanning in targeting the prostate for conformal external beam radiation therapy. The application of this technology to current conformal techniques will allow the reduction of treatment margins in all dimensions. This should diminish treatment-related morbidity and facilitate further dose escalation, resulting in improved cancer control.

A comparison of daily CT localization to a daily ultrasound-based system in prostate cancer.

PURPOSE: Daily CT localization has been demonstrated to be a precise method of correcting radiation field placement by reducing setup and organ motion variations to facilitate dose escalation in prostate carcinoma. The purpose of this study was to evaluate the feasibility and accuracy of daily ultrasound-guided localization utilizing daily CT as a standard. The relatively simple computer-assisted ultrasound-based system is designed to be an efficient means of achieving daily accuracy. METHODS AND MATERIALS: After five weeks of conformal external beam radiation therapy, 23 patients underwent a second CT simulation. Prostate-only fields based on this scan were created with no PTV margin. On each of the final conedown treatment days, a repeat CT simulation and isocenter comparison was performed. Ten of the above patients also underwent prostate localization with a newly developed ultrasound-based system (BAT) that is designed to facilitate patient positioning at the treatment machine. The portable system, which electronically imports the CT simulation target contours and isocenter, is situated adjacent to the treatment couch. Transverse and sagittal suprapubic ultrasound images are captured, and the system overlays the corresponding CT contours relative to the machine isocenter. The CT contours are maneuvered in three dimensions by a touch screen menu to match the ultrasound images. The system then displays the 3-D couch shifts required to produce field alignment. RESULTS: The BAT ultrasound system produced good quality images with minimal operator training required. The localization process was completed in less than 5 min. The absolute magnitude difference between CT and ultrasound was small (A/P range 0 to 5.9 mm, mean 3 mm +/- 1.8; Lat. range 0 to 7.9 mm, mean 2.4 mm +/- 1.8; S/I range 0 to 9 mm, mean 4.6 mm +/- 2.8). Analysis confirmed a significant correlation of isocenter shifts (A/P r = 0.66, p < 0.0001; Lat. r = 0.58, p < 0.003; S/I r = 0.78, p < 0.0001) in all dimensions, and linear regression confirmed the equivalence of the two modalities. CONCLUSIONS: Daily CT localization is a precise method to improve daily target localization in prostate carcinoma. However, it requires significant human and technical resources that limit its widespread applicability. Conversely, localization with the BAT ultrasound system is simple and expeditious by virtue of its ability to image the prostate at the treatment machine in the treatment position. Our initial evaluation revealed ultrasound targeting to be functionally equivalent to CT. This ultrasound technology is promising and warrants further investigation in more patients and at other anatomical sites.

Daily CT localization for correcting portal errors in the treatment of prostate cancer.

INTRODUCTION: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer. METHODS AND MATERIALS: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV1) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV1). The prostate or prostate and seminal vesicles (GTV2) then received 56 Gy to PTV2. All doses were delivered in 2-Gy fractions. After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV3) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field. RESULTS: Utilizing CT-CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm. CONCLUSION: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.

Early stage prostate cancer treated with radiation therapy: stratifying an intermediate risk group.

PURPOSE: This study identifies two early prostate cancer populations within the T1/T2AB, Gleason 2-7, pretreatment prostate specific antigen (PSA) 4-15 ng/ml grouping. By demonstrating different outcomes we may be able to more appropriately select a subgroup for whom adjuvant therapy trials or altered treatment techniques are indicated. MATERIALS AND METHODS: One hundred forty-six patients with T1/T2AB, Gleason score 2-7, PSA 4-15 ng/ml prostate cancer were treated with external beam radiotherapy alone from November 1987 to October 1993. The median pretreatment PSA was 8.6 and the mean 8.7. Minimum follow-up was 2 years with a median of 38 months (mean 42 months, range 24-87). The median age was 70 years (range 58-83) and the median central axis dose delivered was 7240 cGy (mean 7273, range 6541-7895 cGy). Eleven patients received conventional radiotherapy while 135 were treated using conformal techniques. As there is evidence that a low PSA nadir is an early marker for long term biochemical control, time to post treatment PSA < 1 ng/ml was actuarially analyzed by Gleason score, pretreatment PSA, radiation dose, stage, and the presence of perineural invasion. Pretreatment PSA was the only patient characteristic predictive of achieving a PSA level < 1.0 ng/ml. Biochemical relapse free (bNED) control (non rising PSA) was then compared for patients above and below the approximate median pretreatment PSA level of 8 ng/ml. bNED control rates and the time to PSA < 1.0 ng/ml were estimated using Kaplan-Meier methodology, and differences in bNED control and PSA < 1.0 ng/ml according to PSA level were evaluated using the log-rank test. RESULTS: Results from actuarial analysis revealed that pretreatment PSA was the only significant variable predictive of a PSA < 1.0 ng/ml. Ninety-eight percent of patients with pretreatment PSA < 8 achieved a PSA level < 1.0 ng/ml within 3 years compared to 78% for patients with a PSA > 8 ng/ml (p = 0.0003). bNED control for the two groups separated at a pretreatment PSA of 8 ng/ml confirms a favorable outcome, 88% bNED control at 5 years for < 8 ng/ml and 74% for a pretreatment PSA > or = 8 ng/ml (p = 0.007 for overall curve comparison). CONCLUSION: For early prostate cancer patients (T1/T2AB, Gleason 2-7, pretreatment PSA 4-15) there is a significant break in bNED control following external beam radiation at a pretreatment PSA level of 8 ng/ml. Patients with pretreatment PSA < 8 have a very favorable bNED response with radiation alone while those with a pretreatment PSA 8-15 have a significant decrease in bNED response. The 27% failure rate at 5 years in the PSA 8-15 ng/ml patients may justify altered treatment techniques or clinical trials of adjuvant androgen deprivation in this group.

Computed tomography-magnetic resonance image fusion: a clinical evaluation of an innovative approach for improved tumor localization in primary central nervous system lesions.

We describe our initial experience with the AcQSim (Picker International, St. David, PA) computed tomography-magnetic resonance imaging (CT-MRI) fusion software in eight patients with intracranial lesions. MRI data are electronically integrated into the CT-based treatment planning system. Since MRI is superior to CT in identifying intracranial abnormalities, we evaluated the precision and feasibility of this new localization method. Patients initially underwent CT simulation from C2 to the most superior portion of the scalp. T2 and post-contrast T1-weighted MRI of this area was then performed. Patient positioning was duplicated utilizing a head cup and bridge of nose to forehead angle measurements. First, a gross tumor volume (GTV) was identified utilizing the CT (CT/GTV). The CT and MRI scans were subsequently fused utilizing a point pair matching method and a second GTV (CT-MRI/GTV) was contoured with the aid of both studies. The fusion process was uncomplicated and completed in a timely manner. Volumetric analysis revealed the CT-MRI/GTV to be larger than the CT/GTV in all eight cases. The mean CT-MRI/GTV was 28.7 cm3 compared to 16.7 cm3 by CT alone. This translated into a 72% increase in the radiographic tumor volume by CT-MRI. A simulated dose-volume histogram in two patients revealed that marginal portions of the lesion, as identified by CT and MRI, were not included in the high dose treatment volume as contoured with the use of CT alone. Our initial experience with the fusion software demonstrated an improvement in tumor localization with this technique. Based on these patients the use of CT alone for treatment planning purposes in central nervous system (CNS) lesions is inadequate and would result in an unacceptable rate of marginal misses. The importation of MRI data into three-dimensional treatment planning is therefore crucial to accurate tumor localization. The fusion process simplifies and improves precision of this task.