Evaluation of ultrasound-based prostate localization for image-guided radiotherapy

To evaluate the use of the ultrasound-based BAT system for daily prostate alignment.Prostate alignments using the BAT system were compared with alignments using radiographic images of implanted radiopaque markers. The latter alignments were used as a reference. The difference between the BAT and marker alignments represents the displacements that would remain if the alignments were done using ultrasonography. The inter-user variability of the contour alignment process was assessed.On the basis of the marker alignments, the initial displacement of the prostate in the AP, superoinferior, and lateral direction was -0.9 +/- 3.9, 0.1 +/- 3.9, and 0.2 +/- 3.4 mm respectively. The directed differences between the BAT and marker alignments in the respective directions were 0.2 +/- 3.7, 2.7 +/- 3.9, and 1.6 +/- 3.1 mm. The occurrence of displacements >/=5 mm was reduced by a factor of two in the AP direction after the BAT system was used. Among eight users, the average range of couch shifts due to contour alignment variability was 7, 7, and 5 mm in the antero-posterior (AP), superoinferior, and lateral direction, respectively.In our study, the BAT alignments were systematically different from the marker alignments in the superoinferior, and lateral directions. The remaining random variability of the prostate position after the ultrasound-based alignment was similar to the initial variability. However, the occurrence of displacements >/=5 mm was reduced in the AP direction. The inter-user variation of the contour alignment process was significant.     

Comparison of ultrasound and implanted seed marker prostate localization methods: Implications for image-guided radiotherapy

PURPOSE: To analyze two methods of image-guided radiotherapy (IGRT) for external beam radiotherapy of prostate cancer. METHODS AND MATERIALS: The prostate was localized by ultrasound (US) in lateral (left/right), vertical (anteroposterior), and longitudinal (superior/inferior) dimensions and then by fiducial seed marker (SM) kV X-ray. Assuming initial setup to skin marks as the origin, the mean suggested shifts (for all dimensions) were hypothesized to be similar and within 1 mm of the origin. The three-dimensional distance discrepancy between suggested SM and US shift points was calculated. We hypothesized a mean discrepancy >5 mm as clinically significant. RESULTS: From 40 patients, 1019 US/SM measurements were obtained. Lateral, vertical, and longitudinal dimensional comparisons reveal statistically significant differences in mean shifts (p < 0.0001 for all). US dimensional shifts reveal significantly greater variability. The US three-dimensional vector is greater and more variable than the SM vector (p < 0.0001). The mean US/SM three-dimensional distance discrepancy is 8.8 mm (significantly >5 mm, p < 0.0001). CONCLUSIONS: Ultrasound and SM methods suggest different shifts. US data reveal greater systematic/random error vs. SM data. The US data suggest larger PTV expansion margins (approximately 9 mm) are necessary for US IGRT vs. SM IGRT (approximately 3 mm). The hypotheses that US and SM methods suggest similar shifts and that the mean US/SM three-dimensional distance discrepancy is < or =5 mm are rejected.     

A comparison of CT- and ultrasound-based imaging to localize the prostate for external beam radiotherapy

PURPOSE: This study assesses the accuracy of NOMOS B-mode acquisition and targeting system (BAT) compared with computed tomography (CT) in localizing the prostate. METHODS AND MATERIALS: Twenty-six patients were CT scanned, and the prostate was localized by 3 observers using the BAT system. The BAT couch shift measurements were compared with the CT localization. Six of the patients had gold markers present in the prostate, and the prostate movement determined by BAT was compared with the movement determined by the gold markers. RESULTS: Using the BAT system, the 3 observers determined the prostate position to be a mean of 1-5 mm over all directions with respect to the CT. The proportion of readings with a difference >3 mm between the observers was in the range of 25% to 44%. The prostate movement based on gold markers was an average of 3-5 mm different from that measured by BAT. The literature assessing the accuracy and reproducibility on BAT is summarized and compared with our findings. CONCLUSIONS: We have found that there are systematic differences between the BAT-defined prostate position compared with that estimated on CT using gold grain marker seeds.     

Magnetic resonance assessment of prostate localization variability in intensity-modulated radiotherapy for prostate cancer

PURPOSE: To measure prostate motion with magnetic resonance imaging (MRI) during a course of intensity-modulated radiotherapy. METHODS AND MATERIALS: Seven patients with prostate carcinoma were scanned supine on a 1.5-Tesla MRI system with weekly pretreatment and on-treatment HASTE T2-weighted images in 3 orthogonal planes. The bladder and rectal volumes and position of the prostatic midpoint (PMP) and margins relative to the bony pelvis were measured. RESULTS: All pretreatment positions were at the mean position as computed from the on-treatment scans in each patient. The PMP variability (given as 1 SD) in the anterior-posterior (AP), superior-inferior (SI), and right-left (RL) directions was 2.6, 2.4, and 1.0 mm, respectively. The largest variabilities occurred at the posterior (3.2 mm), superior (2.6 mm), and inferior (2.6 mm) margins. A strong correlation was found between large rectal volume (>95th percentile) and anterior PMP displacement. A weak correlation was found between bladder volume and superior PMP displacement. CONCLUSIONS: All pretreatment positions were representative of the subsequent on-treatment positions. A clinical target volume (CTV) expansion of 5.3 mm in any direction was sufficient to ascertain a 95% coverage of the CTV within the planning target volume (PTV), provided that a rectal suppository is administered to avoid rectal overdistension and that the patient has a comfortably filled bladder (<300 mL).     

Implementation and utility of a daily ultrasound-based localization system with intensity-modulated radiotherapy for prostate cancer

: To evaluate the clinical feasibility of daily computer-assisted transabdominal ultrasonography for target position verification in the setting of intensity-modulated radiotherapy (IMRT) for prostate cancer.

: Twenty-three patients with clinically localized prostate cancer were treated using a sequential tomotherapy IMRT technique (Peacock) and daily computer-assisted transabdominal ultrasonography (BAT) for target localization. Patients were instructed to maintain a full bladder and were placed in the supine position using triangulation tattoos and a leg immobilizer to minimize pelvic rotation. The BAT ultrasound system is docked to the treatment collimator and electronically imports the CT simulation target contours and isocenter. The system is able to use the machine isocenter as a reference point to overlay the corresponding CT contours onto the ultrasound images captured in the transverse and sagittal planes. A touch screen menu is used to maneuver the CT contours in three dimensions such that they match the ultrasound images. The system then displays the three-dimensional couch shifts required to produce field alignment. Data were prospectively collected to measure the frequency by which useful ultrasound images were obtained, the amount of time required for localization/setup, and the direction/magnitude of the positional adjustments.

: Of the 23 patients, the BAT ultrasound system produced images of sufficient quality to perform the overlay of the CT contours in 19 patients such that positional verification could be reliably performed. Poor image quality was associated with patient inability to maintain a full bladder, large body habitus, or other anatomic constraints. Of the 19 assessable patients, a total of 185 treatment alignments were performed (mean 8.8/patient). For all cases, the average time required for the daily ultrasound imaging and positional adjustments was 11.9 min. After the initial 5 cases, the user experience skills improved such that the time required for image verification/positional adjustments decreased to a mean of 5.6 min. The average right-left, AP, and cranial-caudal adjustment was 2.6 ± 2.1 mm, 4.7 ± 2.7 mm, and 4.2 ± 2.8 mm, respectively. Positional adjustments >10 mm were infrequent and related primarily to misidentification of the target structures on the ultrasound image, patient movement, or improper registration of the triangulation tattoos.

: Daily computer-assisted BAT ultrasound positional verification of the prostate can be successfully performed through the acquisition of high-quality images in most patients with only a modest increase in treatment setup time. Positional data obtained with this system resulted in clinically meaningful adjustments in daily setup for sequential IMRT that would not be otherwise apparent from other verification modalities.     

Effect of body mass index on shifts in ultrasound-based image-guided intensity-modulated radiation therapy for abdominal malignancies

BACKGROUND AND PURPOSE: We investigated whether corrective shifts determined by daily ultrasound-based image-guidance correlate with body mass index (BMI) of patients treated with image-guided intensity-modulated radiation therapy (IG-IMRT) for abdominal malignancies. The utility of daily image-guidance, particularly for patients with BMI>25.0, is examined. MATERIALS AND METHODS: Total 3162 ultrasound-directed shifts were performed in 86 patients. Direction and magnitude of shifts were correlated with pretreatment BMI. Bivariate statistical analysis and analysis of set-up correction data were performed using systematic and random error calculations. RESULTS: Total 2040 daily alignments were performed. Average 3D vector of set-up correction for all patients was 12.1mm/fraction. Directional and absolute shifts and 3D vector length were significantly different between BMI cohorts. 3D displacement averaged 4.9 mm/fraction and 6.8mm/fraction for BMI < or = 25.0 and BMI>25.0, respectively. Systematic error in all axes and 3D vector was significantly greater for BMI>25.0. Differences in random error were not statistically significant. CONCLUSIONS: Set-up corrections derived from daily ultrasound-based IG-IMRT of abdominal tumors correlated with BMI. Daily image-guidance may improve precision of IMRT delivery with benefits assessed for the entire population, particularly patients with increased habitus. Requisite PTV margins suggested in the absence of daily image-guidance are significantly greater in patients with BMI>25.0.     

Initial experience with ultrasound localization for positioning prostate cancer patients for external beam radiotherapy

: Transabdominal ultrasound localization of the prostate gland and its immediate surrounding anatomy has been used to guide the positioning of patients for the treatment of prostate cancer. This process was evaluated in terms of (1) the reproducibility of the ultrasound measurement; (2) a comparison of patient position between ultrasound localization and skin marks determined from a CT treatment planning scan; (3) the predictive indicators of patient anatomy not well suited for ultrasound localization; (4) the measurement of prostate organ displacement resulting from ultrasound probe pressure; and (5) quality assurance measures.

: The reproducibility of the ultrasound positioning process was evaluated for same-day repeat positioning by the same ultrasound operator (22 patients) and for measurements made by 2 different operators (38 patients). Differences between conventional patient positioning (CT localization with skin markings) and ultrasound-based positioning were determined for 38 patients. The pelvic anatomy was evaluated for 34 patients with pretreatment CT scans to identify predictors of poor ultrasound image quality. The displacement of the prostate resulting from pressure of the ultrasound probe was measured for 16 patients with duplicate CT scans with and without a simulated probe. Finally, daily, monthly, and semiannual quality assurance tests were evaluated.

: Self-verification tests of ultrasound positioning indicated a shift of <3 mm in approximately 95% of cases. Interoperator tests indicated shifts of <3 mm in approximately 80–90% of cases. The mean difference in patient positioning between conventional and ultrasound localization for lateral shifts was 0.3 mm (SD 2.5): vertical, 1.3 mm (SD 4.7 mm) and longitudinal, 1.0 mm (SD 5.1). However, on a single day, the differences were >10 mm in 1.5% of lateral shifts, 7% of longitudinal shifts, and 7% of vertical shifts. The depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis, but not the bladder volume, were significant predictive indicators of poor ultrasound imaging. The pressure of the ultrasound probe displaced the prostate in 7 of the 16 patients by an average distance of 3.1 mm; 9 patients (56%) showed no displacement. Finally, the quality assurance tests detected ultrasound equipment defects.

: The ultrasound positioning system is reproducible and may indicate the need for significant positioning moves. Factors that predict poor image quality are the depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis. The prostate gland may be displaced a small amount by the pressure of the ultrasound probe. A quality assurance program is necessary to detect ultrasound equipment defects that could result in patient alignment errors.     

Ultrasound-based image guided radiotherapy for prostate cancer: comparison of cross-modality and intramodality methods for daily localization during external beam radiotherapy

PURPOSE: To compare two different ultrasound-based verification systems for prostate alignment during daily external beam radiation therapy (EBRT) for localized prostate cancer. METHODS AND MATERIALS: Prostate displacements were measured prospectively in 40 patients undergoing daily EBRT. Comparison was made between a system based on the cross-modality verification method (CMVM), which uses two different imaging modalities to assess organ motion, and a system based on the intramodality verification method (IMVM), which uses only one imaging modality for such assessment. A total of 217 CMVM and 217 IMVM displacements were collected within a minute of each other. In 10 patients, IMVM displacements were also compared with those measured by sequential CT scans. RESULTS: Analysis in the paired CMVM and IMVM displacements shows a significant mean difference of 0.9 +/- 3.3 mm in the lateral and 6.0 +/- 5.1 mm in the superoinferior directions (p < 0.0001), whereas no significant difference was detected in the anteroposterior direction between the two methods. Comparison of the computed tomography scan and IMVM measured displacements shows no significant difference between the two methods, with mean values of 0.2 +/- 1.7 mm in the lateral, -0.3 +/- 1.6 mm in the anteroposterior, and 0.1 +/- 1.4 mm in the superoinferior directions. CONCLUSIONS: A significant systematic difference exists between cross-modality and intramodality methods when assessing prostate alignment during daily EBRT. Because displacements assessed by IMVM are consistent with those assessed by computed tomography scan, a more accurate prostate alignment appears to be obtained when the IMVM method is used.     

Target position variability throughout prostate radiotherapy

Purpose: To quantify the variability in prostate and seminal vesicle position during a course of external beam radiotherapy, and to measure the proportion of target variability due to setup error.

Methods and Materials: Forty-four weekly planning computerized tomography (CT) studies were obtained on six patients undergoing radiotherapy for prostate cancer. All patients were scanned in the radiotherapy treatment position, supine with an empty bladder, with no immobilization device. All organs were outlined on 3-mm-thick axial CT images. Anterior and lateral beam’s eye view digitally reconstructed radiographs and multiplanar reformatted images were generated. The position of the prostate and seminal vesicles relative to the isocenter location as set that day was recorded for each CT study. Target position relative to a bony landmark was measured to determine the relative contribution of setup error to the target position variability.

Results: The seminal vesicle and prostate position variability was most significant in the anterior–posterior (AP) direction, followed by cranial–caudal (CC) and mediolateral (ML) directions. Setup error contributed significantly to the total target position variability. Rectal filling was associated with a trend to anterior movement of the prostate, whereas bladder filling was not associated with any trends. Although most deviations from the target position determined at the initial planning CT scan were within 10 mm, deviations as large as 15 mm and 19 mm were seen in the prostate and seminal vesicles respectively. Target position variations were evenly distributed around the initial target position for some patient studies, but unpredictable patterns were also seen. From a simulation based on the observed variability in target position, the AP, CC, and ML planning target volume (PTV) borders around the clinical target volume (CTV) required for target coverage with 95% certainty are 12.4 mm, 10.3 mm, and 5.6 mm respectively for the prostate and 13.8 mm, 8.6 mm, and 3.9 mm respectively for the seminal vesicles.

Conclusion: Target position variability is significant during prostate radiotherapy, requiring large PTV borders around the CTV. This target position variability may be potentially reduced by improving the setup accuracy.     

Rectal dose variation during the course of image-guided radiation therapy of prostate cancer

Background and purpose

To investigate the change in rectal dose during the treatment course for intensity-modulated radiotherapy (IMRT) of prostate cancer with image-guidance.

Materials and methods

Twenty prostate cancer patients were recruited for this retrospective study. All patients have been treated with IMRT. For each patient, MR and CT images were fused for target and critical structure delineation. IMRT treatment planning was performed on the simulation CT images. Inter-fractional motion during the course of treatment was corrected using a CT-on-rails system. The rectum was outlined on both the original treatment plan and the subsequent daily CT images from the CT-on-rails by the same investigator. Dose distributions on these daily CT images were recalculated with the isocenter shifts relative to the simulation CT images using the leaf sequences/MUs based on the original treatment plan. The rectal doses from the subsequent daily CTs were compared with the original doses planned on the simulation CT using our clinical acceptance criteria.

Results

Based on 20 patients with 139 daily CT sets, 28% of the subsequent treatment dose distributions did not meet our criterion of V₄₀ < 35%, and 27% did not meet our criterion of V₆₅ < 17%. The inter-fractional rectal volume variation is significant for some patients.

Conclusions

Due to the large inter-fractional variation of the rectal volume, it is more favorable to plan prostate IMRT based on an empty rectum and deliver treatment to patients with an empty rectum. Over 70% of actual treatments showed better rectal doses than our clinical acceptance criteria. A significant fraction (27%) of the actual treatments would benefit from adaptive image-guided radiotherapy based on daily CT images.     

Comparison of localization performance with implanted fiducial markers and cone-beam computed tomography for on-line image-guided radiotherapy of the prostate

PURPOSE: The aim of this work was to assess the accuracy of kilovoltage (kV) cone-beam computed tomography (CBCT)-based setup corrections as compared with orthogonal megavoltage (MV) portal image-based corrections for patients undergoing external-beam radiotherapy of the prostate. METHODS AND MATERIALS: Daily cone-beam CT volumetric images were acquired after setup for patients with three intraprostatic fiducial markers. The estimated couch shifts were compared retrospectively to patient adjustments based on two orthogonal MV portal images (the current clinical standard of care in our institution). The CBCT soft-tissue based shifts were also estimated by digitally removing the gold markers in each projection to suppress the artifacts in the reconstructed volumes. A total of 256 volumetric images for 15 patients were analyzed. RESULTS: The Pearson coefficient of correlation for the patient position shifts using fiducial markers in MV vs. kV was (R2 = 0.95, 0.84, 0.81) in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The correlation using soft-tissue matching was as follows: R2 = 0.90, 0.49, 0.51 in the LR, AP and SI directions. A Bland-Altman analysis showed no significant trends in the data. The percentage of shifts within a +/-3-mm tolerance (the clinical action level) was 99.7%, 95.5%, 91.3% for fiducial marker matching and 99.5%, 70.3%, 78.4% for soft-tissue matching. CONCLUSIONS: Cone-beam CT is an accurate and precise tool for image guidance. It provides an equivalent means of patient setup correction for prostate patients with implanted gold fiducial markers. Use of the additional information provided by the visualization of soft-tissue structures is an active area of research.     

Daily ultrasound-based image-guided targeting for radiotherapy of upper abdominal malignancies

PURPOSE: Development and implementation of a strategy to use a stereotactic ultrasound (US)-based image-guided targeting device (BAT) to align intensity-modulated radiotherapy (IMRT) target volumes accurately in the upper abdomen. Because the outlines of such targets may be poorly visualized by US, we present a method that uses adjacent vascular guidance structures as surrogates for the target position. We assessed the potential for improvement of daily repositioning and the feasibility of daily application. METHODS AND MATERIALS: A total of 62 patients were treated by sequential tomotherapeutic IMRT between October 2000 and June 2003 for cholangiocarcinoma and gallbladder carcinoma (n = 10), hepatocellular carcinoma (n = 10), liver metastases (n = 11), pancreatic carcinoma (n = 20), neuroblastoma (n = 3), and other abdominal and retroperitoneal tumors (n = 8). The target volumes (TVs) and organs at risk were delineated in contrast-enhanced CT data sets. Additionally, vascular guidance structures in close anatomic relation to the TV, or within the TV, were delineated. Throughout the course of IMRT, US BAT images were acquired during daily treatment positioning. In addition to the anatomic structures typically used for US targeting (e.g., the TV and dose-limiting organs at risk), CT contours of guidance structures were superimposed onto the real-time acquired axial and sagittal US images, and target position adjustments, as indicated by the system, were performed accordingly. We report the BAT-derived distribution of shifts in the three principal room axes compared with a skin-mark-based setup, as well as the time required to perform BAT alignment. The capability of the presented method to improve target alignment was assessed in 15 patients by comparing the organ and fiducial position between the respective treatment simulation CT with a control CT study after US targeting in the CT suite. RESULTS: A total of 1,337 BAT alignments were attempted. US images were not useful in 56 setups (4.2%), mainly because of limited visibility due to daily variations in colonic and gastric air. US imaging was facilitated in intrahepatic tumors and asthenic patients. The mean +/- SD shift from the skin mark position was 4.9 +/- 4.35, 6.0 +/- 5.31, and 6.0 +/- 6.7 mm in the x, y, and z direction, respectively. The mean magnitude vector of three-dimensional alignment correction was 11.4 +/- 7.6 mm. The proportion of daily alignments corrected by a magnitude of >10, >15, and >20 mm was 48.9%, 25.1%, and 12.7%, respectively. The magnitude of shifts in the principal directions, as well as the three-dimensional vector of displacement, was statistically significant (test against the zero hypothesis) at p <0.0001. The guidance structures that were the most valuable for identification of the TV position were the branches of the portal vein, hepatic artery, and dilated bile ducts in intrahepatic lesions and the aorta, celiac trunk, superior mesenteric artery, and extrahepatic aspects of the portal vein system in retroperitoneal and extrahepatic lesions. The mean total setup time was 4.6 min. The correlation of BAT targeting with target setup error assessment in the control CT scans in 15 patients revealed setup error reduction in 14 of 15 alignments. The average setup error reduction, assessed as a reduction in the length of setup error three-dimensional magnitude vector, was 54.4% +/- 26.9%, with an observed mean magnitude of residual setup error of 4.6 +/- 3.4 mm. The sole worsening of an initial setup was by a magnitude of <2 mm. US targeting resulted in statistically significant improvements in patient setup (p = 0.03). CONCLUSION: Daily US-guided BAT targeting for patients with upper abdominal tumors was feasible in the vast majority of attempted setups. This method of US-based image-guided tumor targeting has been successfully implemented in clinical routine. The observed improved daily repositioning accuracy might allow for individualized reduction of safety margins and optional dose escalation. Compared with the established application of the BAT device for prostate radiotherapy, in which the target can be directly visualized, the TV in the present study was predominantly positioned relative to guidance vascular structures in close anatomic relation. We perceived an enormous potential in improved and individualized patient positioning for fractionated radiotherapy and also for stereotactic extracranial radiotherapy and radiosurgery, especially for tumors of the liver and pancreas.