Automatic localization of the prostate for on-line or off-line image-guided radiotherapy

PURPOSE: With higher radiation dose, higher cure rates have been reported in prostate cancer patients. The extra margin needed to account for prostate motion, however, limits the level of dose escalation, because of the presence of surrounding organs at risk. Knowledge of the precise position of the prostate would allow significant reduction of the treatment field. Better localization of the prostate at the time of treatment is therefore needed, e.g. using a cone-beam computed tomography (CT) system integrated with the linear accelerator. Localization of the prostate relies upon manual delineation of contours in successive axial CT slices or interactive alignment and is fairly time-consuming. A faster method is required for on-line or off-line image-guided radiotherapy, because of prostate motion, for patient throughput and efficiency. Therefore, we developed an automatic method to localize the prostate, based on 3D gray value registration. METHODS AND MATERIALS: A study was performed on conventional repeat CT scans of 19 prostate cancer patients to develop the methodology to localize the prostate. For each patient, 8-13 repeat CT scans were made during the course of treatment. First, the planning CT scan and the repeat CT scan were registered onto the rigid bony structures. Then, the delineated prostate in the planning CT scan was enlarged by an optimum margin of 5 mm to define a region of interest in the planning CT scan that contained enough gray value information for registration. Subsequently, this region was automatically registered to a repeat CT scan using 3D gray value registration to localize the prostate. The performance of automatic prostate localization was compared to prostate localization using contours. Therefore, a reference set was generated by registering the delineated contours of the prostates in all scans of all patients. Gray value registrations that showed large differences with respect to contour registrations were detected with a chi(2) analysis and were removed from the data set before further analysis. RESULTS: Comparing gray value registration to contour registration, we found a success rate of 91%. The accuracy for rotations around the left-right, cranial-caudal, and anterior-posterior axis was 2.4 degrees, 1.6 degrees, and 1.3 degrees (1 SD), respectively, and for translations along these axes 0.7, 1.3, and 1.2 mm (1 SD), respectively. A large part of the error is attributed to uncertainty in the reference contour set. Automatic prostate localization takes about 45 seconds on a 1.7 GHz Pentium IV personal computer. CONCLUSIONS: This newly developed method localizes the prostate quickly, accurately, and with a good success rate, although visual inspection is still needed to detect outliers. With this approach, it will be possible to correct on-line or off-line for prostate movement. Combined with the conformity of intensity-modulated dose distributions, this method might permit dose escalation beyond that of current conformal approaches, because margins can be safely reduced.     

Positioning errors and prostate motion during conformal prostate radiotherapy using on-line isocentre set-up verification and implanted prostate markers.

PURPOSE: To evaluate treatment errors from set-up and inter-fraction prostatic motion with port films and implanted prostate fiducial markers during conformal radiotherapy for localized prostate cancer. METHODS: Errors from isocentre positioning and inter-fraction prostate motion were investigated in 13 men treated with escalated dose conformal radiotherapy for localized prostate cancer. To limit the effect of inter-fraction prostate motion, patients were planned and treated with an empty rectum and a comfortably full bladder, and were instructed regarding dietary management, fluid intake and laxative use. Field placement was determined and corrected with daily on-line portal imaging. A lateral portal film was taken three times weekly over the course of therapy. From these films, random and systematic placement errors were measured by matching corresponding bony landmarks to the simulator film. Superior-inferior and anterior-posterior prostate motion was measured from the displacement of three gold pins implanted into the prostate before planning. A planning target volume (PTV) was derived to account for the measured prostate motion and field placement errors. RESULTS: From 272 port films the random and systematic isocentre positioning error was 2.2 mm (range 0.2-7.3 mm) and 1.4 mm (range 0.2-3.3 mm), respectively. Prostate motion was largest at the base compared to the apex. Base: anterior, standard deviation (SD) 2.9 mm; superior, SD 2.1 mm. Apex: anterior, SD 2.1 mm; superior, SD 2.1 mm. The margin of PTV required to give a 99% probability of the gland remaining within the 95% isodose line during the course of therapy is superior 5.8 mm, and inferior 5.6 mm. In the anterior and posterior direction, this margin is 7.2 mm at the base, 6.5 mm at the mid-gland and 6.0 mm at the apex. CONCLUSIONS: Systematic set-up errors were small using real-time isocentre placement corrections. Patient instruction to help control variation in bladder and rectal distension during therapy may explain the observed small SD for prostate motion in this group of patients. Inter-fraction prostate motion remained the largest source of treatment error, and observed motion was greatest at the gland base. In the absence of real-time pre-treatment imaging of prostate position, sequential portal films of implanted prostatic markers should improve quality assurance by confirming organ position within the treatment field over the course of therapy.     

前列腺癌放疗的摆位误差分析

目的 探讨前列腺癌仰卧位放疗时左右、头脚、前后方向的摆位误差及各方向的旋转误差。方法 收集2011年10月至2013年6月接受前列腺癌根治性放疗的患者25例,采用仰卧位体模固定,锥形束CT（CBCT）骨配准校位,分析左右、头脚、前后方向的平均摆位误差及各方向的平均旋转误差。结果 全放疗疗程中每例患者校位9次,共计225次。各方向的平均摆位误差：左右（0.19±0.18）cm,头脚（0.36±0.30）cm,前后（0.21±0.16）cm;其中左右方向摆位误差≥5mm占5.8%,头脚占24.3%,前后占8.0%。各方向旋转误差：轴位（1.07±1.03）°,头脚（0.82±0.66）°,水平（0.79±0.68）°。前5次与后4次摆位及旋转误差比较差异无统计学意义（P＞0.05）。结论前列腺癌仰卧位放疗时,头脚摆位误差最大,左右及前后摆位误差相当,旋转误差较小可忽略不计。     

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.     

在线千伏级锥形束CT引导前列腺癌调强放疗摆位误差研究

目的 通过千伏级锥形束CT(KV-CBCT)在线测量前列腺癌调强放疗的摆位误差及图像引导后的残余误差,确定前列腺癌患者外照射治疗计划中CTV外放PTV的边界大小.方法 入选7例接受根治性调强放疗的前列腺癌患者,每例患者每周至少行KV-CBCT在线校正治疗体位2次.采用常规皮肤标记激光对位后采集图像,将所获得CBCT与计划CT图像进行灰度自动配准.计算摆位误差并进行在线评价,若摆位误差＞2 mm则调整治疗床进行纠正.纠正后重新采集CBCT图像进行配准,计算残余误差.根据摆位误差和残余误差分别计算纠正前后临床靶体积(CTV)至计划靶体积(PTV)外放边界大小.结果 共获取197幅KV-CBCT图像.7例患者左右、头脚、前后方向系统误差和随机误差分别为3.1和2.1、1.5和1.8、4.2和3.7 mm,外放边界分别为9.3、5.1、13.0 mm.经KV-CBCT引导纠正后左右、头脚、前后方向系统残余误差和随机残余误差分别为1.1和0.9、0.7和1.1、1.1和1.3 mm,外放边界分别为3.4、2.5、3.7 mm.结论 在线KV-CBCT引导放疗技术可减小前列腺癌患者摆位误差、提高摆位精度,CTV外放PTV边界可缩小至3～4 mm.     

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.     

Automatic target localization and verification for on-line image-guided stereotactic body radiotherapy of the spine

To facilitate image-guided stereotactic body radiotherapy (IG-SBRT) of spinal and paraspinal tumors, the authors have developed an on-line image registration system for automated target localization and patient position verification with high precision. When rotations are present in a patient's daily setup position, a setup error of a few millimeters can be introduced in localization of the isocenter by using surrounding bony structures. This setup error not only will deteriorate the dose coverage of the tumor, more importantly it will overdose the spinal cord. To resolve this issue, the image registration program developed by the authors detects translational shifts as well as rotational shifts using 3D CT image registration. Unacceptable rotations were corrected by either repositioning the patient or adjusting the treatment couch that was capable of rotational corrections when such a couch was available for clinical use. One pair of orthogonal digitally reconstructed radiographs (DRR) were generated from the daily pretreatment CT scan to compare with the corresponding DRRs generated from the planning CT scan to confirm the target shift correction. After the patient's position was corrected a pair of orthogonal portal images were taken for final verification. The accuracy of the image registration result was found to be within 0.1 mm on a head and neck phantom. Target shifts of a fraction of a millimeter were readily visible in our DRR comparison and portal image verification. The time needed to complete the image registration and DRR comparison was about 3 minutes. An integrated system that combines a high-speed CT scanner and a linear accelerator was used for imaging and treatment delivery. Application of the program in actual IG-SBRT cases demonstrated that it was accurate, fast, and reliable. It serves as a useful tool for image-guided radiotherapy where high precision of target localization is required.     

Impact of probe pressure variability on prostate localization for ultrasound-based image-guided radiotherapy

Purpose

To evaluate the impact of transabdominal probe pressure on prostate positioning with an intramodality ultrasound (US) image-guided-radiotherapy system and to quantify pressure variability over the treatment course.

Material and methods

8 prostate cancer patients (group A) and 17 healthy volunteers underwent 3 consecutive US images with increasing probe pressure levels, and 1 CT acquisition for the group A only. Prostate positions were compared after manual registration of the first US image contour projected on 2 others. Group A’s pressure levels were quantified by measuring skin-to-skin distances between corresponding CT–US images. The same methodology was used on paired CT/CBCT–US images acquired during treatments of 18 prostate cancer patients to determine whether the different pressure levels applied to the group A were close to the clinical practices and to quantify pressure variability along the treatment course.

Results

84% of 3D prostate displacements were above 2 mm for at least one pressure level. Probe pressures deliberately applied were similar to the ones observed clinically. The latter drastically varied between sessions.

Conclusion

Even with an intramodality system, probe pressure can impact prostate localization because of the pressure variability along the treatment course. Therefore, margins should be expanded from 0.5 to 1.2 mm to ensure treatment accuracy.     

Automatic prostate localization on cone-beam CT scans for high precision image-guided radiotherapy

PURPOSE: Previously, we developed an automatic three-dimensional gray-value registration (GR) method for fast prostate localization that could be used during online or offline image-guided radiotherapy. The method was tested on conventional computed tomography (CT) scans. In this study, the performance of the algorithm to localize the prostate on cone-beam CT (CBCT) scans acquired on the treatment machine was evaluated. METHODS AND MATERIALS: Five to 17 CBCT scans of 32 prostate cancer patients (332 scans in total) were used. For 18 patients (190 CBCT scans), the CBCT scans were acquired with a collimated field of view (FOV) (craniocaudal). This procedure improved the image quality considerably. The prostate (i.e., prostate plus seminal vesicles) in each CBCT scan was registered to the prostate in the planning CT scan by automatic 3D gray-value registration (normal GR) starting from a registration on the bony anatomy. When these failed, registrations were repeated with a fixed rotation point locked at the prostate apex (fixed apex GR). Registrations were visually assessed in 3D by one observer with the help of an expansion (by 3.6 mm) of the delineated prostate contours of the planning CT scan. The percentage of successfully registered cases was determined from the combined normal and fixed apex GR assessment results. The error in gray-value registration for both registration methods was determined from the position of one clearly defined calcification in the prostate gland (9 patients, 71 successful registrations). Results: The percentage of successfully registered CBCT scans that were acquired with a collimated FOV was about 10% higher than for CBCT scans that were acquired with an uncollimated FOV. For CBCT scans that were acquired with a collimated FOV, the percentage of successfully registered cases improved from 65%, when only normal GR was applied, to 83% when the results of normal and fixed apex GR were combined. Gray-value registration mainly failed (or registrations were difficult to assess) because of streaks in the CBCT scans caused by moving gas pockets in the rectum during CBCT image acquisition (i.e., intrafraction motion). The error in gray-value registration along the left-right, craniocaudal, and anteroposterior axes was 1.0, 2.4, and 2.3 mm (1 SD) for normal GR, and 1.0, 2.0, and 1.7 mm (1 SD) for fixed apex GR. The systematic and random components of these SDs contributed approximately equally to these SDs, for both registration methods. Conclusions: The feasibility of automatic prostate localization on CBCT scans acquired on the treatment machine using an adaptation of the previously developed three-dimensional gray-value registration algorithm, has been validated in this study. Collimating the FOV during CBCT image acquisition improved the CBCT image quality considerably. Artifacts in the CBCT images caused by large moving gas pockets during CBCT image acquisition were the main cause for unsuccessful registration. From this study, we can conclude that CBCT scans are suitable for online and offline position verification of the prostate, as long as the amount of nonstationary gas is limited.     

Optimal control of set-up margins and internal margins for intra- and extracranial radiotherapy using stereoscopic kilovoltage imaging.

In this paper the clinical introduction of stereoscopic kV-imaging in combination with a 6 degrees-of-freedom (6 DOF) robotics system and breathing synchronized irradiation will be discussed in view of optimally reducing interfractional as well as intrafractional geometric uncertainties in conformal radiation therapy. Extracranial cases represent approximately 70% of the patient population on the NOVALIS treatment machine (BrainLAB A.G., Germany) at the AZ-VUB, which is largely due to the efficiency of the real-time positioning features of the kV-imaging system. The prostate case will be used as an example of those target volumes showing considerable changes in position from day-to-day, yet with negligible motion during the actual course of the treatment. As such it will be used to illustrate the on-line target localization using kV-imaging and 6 DOF patient adjustment with and without implanted radio-opaque markers prior to treatment. Small lung lesion will be used to illustrate the system's potential to synchronize the irradiation with breathing in coping with intrafractional organ motion.     

Impact of planning target volume margins and rectal distention on biochemical failure in image-guided radiotherapy of prostate cancer

Background and purpose

A previous study in our department demonstrated the negative impact on freedom from biochemical failure (FFBF) of using too narrow planning target volume (PTV) margins during prostate image-guided radiotherapy (IGRT). Here, we investigated the impact of appropriate PTV margins and rectal distention on FFBF.

Methods and materials

A total of 50 T1-T3N0M0 prostate cancer patients were treated with daily IGRT by implanted markers. In the first 25 patients, PTV margins were 3 mm laterolateral, 5 mm anterioposterior and 4 mm craniocaudal. The subsequent 25 patients were treated with isotropic margins of 6 mm. The rectal cross-sectional area (CSA) was determined on the planning CT. Median follow-up was 61 months.

Results

The overall 5-year FFBF was 83%. A 6 mm PTV margin was related to increased 5-year FFBF on univariate analysis (96% vs 74% with the tighter PTV margins, p = 0.04). The 5-year FFBF of patients with a rectal distention on the planning CT was worse compared to those with limited rectal filling (75% for CSA ? 9 cm² vs 89% for CSA < 9 cm², p = 0.02), which remained significant on multivariate analysis (p = 0.04).

Conclusion

This retrospective study illustrated the positive impact of PTV margin adaptation and addressed the importance of avoiding rectal distention at time of the planning CT.     

Commissioning an image-guided localization system for radiotherapy

PURPOSE: To describe the design and commissioning of a system for the treatment of classes of tumors that require highly accurate target localization during a course of fractionated external-beam therapy. This system uses image-guided localization techniques in the linac vault to position patients being treated for cranial tumors using stereotactic radiotherapy, conformal radiotherapy, and intensity-modulated radiation therapy techniques. Design constraints included flexibility in the use of treatment-planning software, accuracy and precision of repeat localization, limits on the time and human resources needed to use the system, and ease of use. METHODS AND MATERIALS: A commercially marketed, stereotactic radiotherapy system, based on a system designed at the University of Florida, Gainesville, was adapted for use at the University of Washington Medical Center. A stereo pair of cameras in the linac vault were used to detect the position and orientation of an array of fiducial markers that are attached to a patient's biteblock. The system was modified to allow the use of either a treatment-planning system designed for stereotactic treatments, or a general, three-dimensional radiation therapy planning program. Measurements of the precision and accuracy of the target localization, dose delivery, and patient positioning were made using a number of different jigs and devices. Procedures were developed for the safe and accurate clinical use of the system. RESULTS: The accuracy of the target localization is comparable to that of other treatment-planning systems. Gantry sag, which cannot be improved, was measured to be 1.7 mm, which had the effect of broadening the dose distribution, as confirmed by a comparison of measurement and calculation. The accuracy of positioning a target point in the radiation field was 1.0 +/- 0.2 mm. The calibration procedure using the room-based lasers had an accuracy of 0.76 mm, and using a floor-based radiosurgery system it was 0.73 mm. Target localization error in a phantom was 0.64 +/- 0.77 mm. Errors in positioning due to couch rotation error were reduced using the system. CONCLUSION: The system described has proven to have acceptable accuracy and precision for the clinical goals for which it was designed. It is robust in detecting errors, and it requires only a nominal increase in setup time and effort. Future work will focus on evaluating its suitability for use in the treatment of head-and-neck cancers not contained within the cranial vault.     

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.     

Organ motion, set-up variation and treatment margins in radical radiotherapy of urinary bladder cancer.

BACKGROUND AND PURPOSE: A major challenge in conformal radiotherapy of bladder cancer is to determine adequate treatment margins. For this purpose, we therefore quantified the internal motion of the urinary bladder as well as the external patient set-up variation during a course of fractionated radiotherapy. In the light of the recently introduced ICRU-62 concept, the planning organ at risk volume, we also studied the internal motion of nearby organs at risk, the rectum and intestine. MATERIAL AND METHODS: Weekly CT scans and electronic portal images (EPIs) were sampled from 20 patients during radical, conformal bladder irradiation (60-64 Gy/2 Gy in five fractions weekly). The planning scans were acquired with 70 ml of bladder contrast instilled, and patients were instructed to void before the treatment/repeat scanning sessions. Internal motion of the bladder, rectum and intestine was measured by 3-D image matching of the repeat scans to the patients' planning scans. Internal margins (CTV-to-ITV) were determined using both a direct empirical approach and an analytically derived margin recipe. The external patient set-up variability was determined by 2-D matching of front and lateral EPIs to corresponding digitally reconstructed radiographs. RESULTS: A total of 149 CT scans (20 for planning, 129 during the treatment course) and 133 sets of EPIs were analysed. Bladder volumes were smaller during treatment than in the planning situation in 85% of the repeat scans. Nevertheless, we found the repeat scan bladder volumes to extend outside the planning scan bladder contours in 89% of the scans, on average with 9% of the volume (range: 0-47%). Eight patients (40%) had at least one repeat scan (25 scans in total) where displacements >15 mm were observed at one or more sides of the bladder. CTV-to-ITV margins of 10 mm inferior, 20 mm superior, 11 mm left, 8 mm right, 20 mm anterior and 14 mm posterior were required to simultaneously encompass all bladder deflections except for the largest outward deflection in all directions in 84% of the patients. Including patient set-up variation (CTV-to-PTV), we found that an additional safety margin of 2-6 mm had to be added in the various directions. The rectum expanded outside the planning contours in all repeat scans, on average with 24% of the volume (range: 2-69%). The volume of intestine found close to the bladder were significantly and negatively correlated to the bladder volume in almost half of the patients. CONCLUSION: This study documented both a large internal motion of the bladder and a substantial patient set-up variation. Our current treatment margins have been adjusted according to the findings of this study. Considerable variation in position and volume of the rectum and intestine was also documented.