Prostate Rotation Research Articles

Comparing adaptation strategies in MRI-guided online adaptive radiotherapy for prostate cancer: Implications for treatment margins

PurposeTo quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate carcinoma (PCa) by evaluating the margins required to accommodate intra-fraction motion of the clinical target volumes for prostate (CTVpros), prostate including seminal vesicles (CTVpros + sv) and gross tumor volume (GTV). Materials and methodsClinical delineations of the CTVpros, CTVpros + sv and GTV of 24 patients with intermediate- and high-risk PCa, treated using ATS on a 1.5 T MR-Linac, were used for analysis. Delineations were available pre- and during beam-on. To simulate ATP and ATR workflows, we automatically generated the structures associated with these workflows using rigid transformations from the planning-MRI to the daily online MRIs. Clinical GTVs were analyzed as ATR GTVs and only ATP GTVs were simulated. Planning target volumes (PTVs) were generated with isotropic margins ranging 0.0–5.0 mm. The volumetric overlap was calculated between these PTVs and their corresponding clinical delineation on the MRI acquired during beam-on and averaged over all treatment fractions. ResultsThe PTV margin required to cover > 95% of the CTVpros was equal (2.5 mm) for all workflows. For the CTVpros + sv, this margin increased to 5.0, 4.0 and 3.5 mm in the ATP, ATR and ATS workflow, respectively. GTV coverage improved from ATP to ATR for margins up to 4.0 mm. ConclusionATP, ATR and ATS workflows ensure equal coverage of the CTVpros for the current clinical margins. For the CTVpros + sv, ATS showed optimal performance. GTV coverage improves by additional adaptations to prostate rotations.

The dosimetric error due to uncorrected tumor rotation during real-time adaptive prostate stereotactic body radiation therapy.

During prostate stereotactic body radiation therapy (SBRT), prostate tumor translational motion may deteriorate the planned dose distribution. Most of the major advances in motion management to date have focused on correcting this one aspect of the tumor motion, translation. However, large prostate rotation up to 30° has been measured. As the technological innovation evolves toward delivering increasingly precise radiotherapy, it is important to quantify the clinical benefit of translational and rotational motion correction over translational motion correctionalone. The purpose of this work was to quantify the dosimetric impact of intrafractional dynamic rotation of the prostate measured with a six degrees-of-freedom tumor motion monitoringtechnology. The delivered dose was reconstructed including (a) translational and rotational motion and (b) only translational motion of the tumor for 32 prostate cancer patients recruited on a 5-fraction prostate SBRT clinical trial. Patients on the trial received 7.25 Gy in a treatment fraction. A 5 mm clinical target volume (CTV) to planning target volume (PTV) margin was applied in all directions except the posterior direction where a 3 mm expansion was used. Prostate intrafractional translational motion was managed using a gating strategy, and any translation above the gating threshold was corrected by applying an equivalent couch shift. The residual translational motion is denoted as . Prostate intrafractional rotational motion was recorded but not corrected. The dose differences from the planned dose due to + , ΔD( + ) and due to alone, ΔD( ), were then determined for CTV D98, PTV D95, bladder V6Gy, and rectum V6Gy. The residual dose error due to uncorrected rotation, was then quantified: = ΔD( + ) - ΔD( ). Fractional data analysis shows that the dose differences from the plan (both ΔD( + ) and ΔD( )) for CTV D98 was less than 5% in all treatment fractions. ΔD( + ) was larger than 5% in one fraction for PTV D95, in one fraction for bladder V6Gy, and in five fractions for rectum V6Gy. Uncorrected rotation, induced residual dose error, , resulted in less dose to CTV and PTV in 43% and 59% treatment fractions, respectively, and more dose to bladder and rectum in 51% and 53% treatment fractions, respectively. The cumulative dose over five fractions, ∑D( + ) and ∑D( ), was always within 5% of the planned dose for all four structures for everypatient. The dosimetric impact of tumor rotation on a large prostate cancer patient cohort was quantified in this study. These results suggest that the standard 3-5 mm CTV-PTV margin was sufficient to account for the intrafraction prostate rotation observed for this cohort of patients, provided an appropriate gating threshold was applied to correct for translational motion. Residual dose errors due to uncorrected prostate rotation were small in magnitude, which may be corrected using different treatment adaptation strategies to further improve the dosimetricaccuracy.

Dosimetric impact of interfraction prostate and seminal vesicle volume changes and rotation: A post-hoc analysis of a phase III randomized trial of MRI-guided versus CT-guided stereotactic body radiotherapy

Background and purposeInterfraction volumetric changes/rotations in the prostate and proximal seminal vesicles (SVs) might compromise target coverage when tight margins are used for prostate stereotactic body radiotherapy (SBRT). We investigated on-board MRI images from MRI-guided SBRT to better understand this. Materials and methodsTwenty consecutive patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) enrolled on the MRI arm of a phase III randomized trial were included. A 2 mm isotropic margin was used for prostate and proximal SVPTV. Target volume, prostate dimensions, angles of the proximal SV on axial (angle α) and sagittal view (angle θ) were measured on a 0.35 T simulation MRI and five on-board pre-treatment MRIs. Dice coefficient of the targets and target dosimetry were calculated. ResultsAll patients experienced an isotropic increase in prostate volume during SBRT (p = 0.0016): 0.1%, 9.0%, 12.1%, 15.1%, and 14.2% (median) at fractions 1–5, respectively, regardless of baseline volume, which was significantly reduced with neoadjuvant ADT (p = 0.0042). There was minimal interfraction rotation of prostate, however, considerable variations in proximal SV angle α (median 21.5°) and angle θ (median 17.6°) were seen. Median V100% was 97.5% and 87.1% for prostate and proximal SV CTV, respectively. V95%≥95% was achieved in 94% of fractions for the prostate and in 59% for proximal SV. ConclusionProstate volume consistently increased during SBRT. Interfraction prostatic rotation was minimal while rotation of the proximal SV was considerable. Prostate dosimetry was favorable, but online adaptive therapy may be indicated occasionally to account for prostatic swelling and in particular proximal SV rotations.

Dosimetric impact of intrafraction prostate rotation and accuracy of gating, multi-leaf collimator tracking and couch tracking to manage rotation: An end-to-end validation using volumetric film measurements

Background and purposeBoth gating and tracking can mitigate the deteriorating dosimetric impact of intrafraction translation during prostate stereotactic body radiotherapy (SBRT). However, their ability to manage intrafraction rotation has not yet been thoroughly investigated. The dosimetric accuracy of gating, MLC tracking and couch tracking to manage intrafraction prostate rotation was investigated. Materials and methodsTreatment plans for end-to-end tests of prostate SBRT with focal boosting were generated for a dynamic anthropomorphic pelvis phantom. The phantom applied internal lateral rotation (up to 25°) and coupled vertical and longitudinal translation of a radiochromic film stack that was used for dose measurements. Dose was delivered for each plan while the phantom applied motion according to three typical prostate motion traces without compensation (i), with gating (ii), with MLC tracking (iii) or with couch tracking (iv). Measured doses for the four motion compensation strategies were compared with the planned dose in terms of γ-index analysis, target coverage and organs at risk (OAR) sparing. ResultsIntrafraction rotation reduced the 3%(global)/2mm γ-index passing rate (γPR) for the prostate target volume by median (range) –33.2% (−68.6%, −4.1%) when no motion compensation was applied. The use of motion compensation improved the γPR by 13.2% (−0.4%, 32.9%) for gating, by 6.0% (−0.8%, 27.7%) for MLC tracking and by 11.1% (1.2%, 22.9%) for couch tracking. The three compensation techniques improved the target coverage in most cases. Gating showed better OAR sparing than MLC tracking or couch tracking. ConclusionsCompensation of intrafraction prostate rotation with gating, MLC tracking and couch tracking was investigated experimentally for the first time. All three techniques improved the dosimetric accuracy, but residual motion-related dose errors remained due to the lack of rotation correction.

PO-1591: Dosimetric accuracy of beam gating, MLC tracking and couch tracking to manage prostate rotation

PO-1591: Dosimetric accuracy of beam gating, MLC tracking and couch tracking to manage prostate rotation

Experimental evaluation of the dosimetric impact of intrafraction prostate rotation using film measurement with a 6DoF robotic arm.

Tumor motion during radiotherapy can cause a reduction in target dose coverage and an increase in healthy tissue exposure. Tumor motion is not strictly translational and often exhibits complex six degree-of-freedom (6DoF) translational and rotational motion. Although the dosimetric impact of prostate tumor translational motion is well investigated, the dosimetric impact of 6DoF motion has only been studied with simulations or dose reconstruction. This study aims to experimentally quantify the dose error caused by 6DoF motion. The experiment was designed to test the hypothesis that 6DoF motion would cause larger dose errors than translational motion alone through gamma analyses of two-dimensional film measurements. Four patient-measured intrafraction prostate motion traces and four VMAT 7.25Gy/Fx SBRT treatment plans were selected for the experiment. The traces represented typical motion patterns, including small-angle rotations (<4°), transient movement, persistent excursion, and erratic rotations (>6°). Gafchromic film was placed inside a custom-designed phantom, held by a high-precision 6DoF robotic arm for dose measurements in the coronal plane during treatment delivery. For each combination of the motion trace and treatment plan, two film measurements were made, one with 6DoF motion and the other with the three-dimensional (3D) translation components of the same trace. A gamma pass rate criteria of 2% relative dose/2mm distance-to-agreement was used in this study and evaluated for each measurement with respect to the static reference film. Two test thresholds, 90% and 50% of the reference dose, were applied to investigate the difference in dose coverage for the PTV region and surrounding areas, respectively. The hypothesis was tested using a Wilcoxon signed-rank test. For each of the 16 plan and motion trace pairs, a reduction in the gamma pass rate was observed for 6DoF motion compared with 3D translational motion. With 90% gamma-test threshold, the reduction was 5.8%±7.1% (P<0.01). With 50% gamma-test threshold, the reduction was 4.1%±4.8% (P<0.01). For the first time, the dosimetric impact of intrafraction prostate rotation during SBRT treatment was measured experimentally. The experimental results support the hypothesis that 6DoF tumor motion causes higher dose error than translation motion alone.

Margin Reduction by Virtual Couch Shift in Prostate SBRT on a 1.5T MR-Linac

We treat localized prostate cancer on a 1.5T MR-Linac using plan re-optimization to the anatomy of the day in each fraction. We investigated the efficacy of a 2-stage, clinically available workflow to reduce intrafraction motion during the 40-minute patient on-couch time and potential margin reduction. Patients with intermediate risk prostate cancer (NCNN classification) were treated with 5 x 7.25 Gy on an MRL. Each fraction, an initial T2 weighed MR scan (‘INI’, 2 min scan time) was acquired, and pre-treatment contours were propagated and manually adapted to this scan, thus correcting for prostate rotation and organ deformation. Next, dose re-optimization (7 beam IMRT) was applied (Monaco treatment planning system), with a 5 mm CTV-PTV margin. Because the average time between the initial scan and beam on is approximately 30 minutes, prostate intrafraction motion can be considerable. Therefore, during the last minutes of this process, a position verification (‘PV’) MR scan was obtained to determine this motion. In our initial treatments (group 1, 26 patients) a virtual couch shift (VCS) was applied if part of the prostate was outside the PTV, (i.e., a prostate shift > 5 mm). The VCS involved a translation of the planned dose according to the PV to INI scan registration of the prostate, using a fast re-optimization method. In the subsequent 25 patients (group 2), the VCS was always applied, also for shifts below 5 mm, to further reduce the impact of pre-delivery intrafraction motion. Next, the plan was delivered in typically 7 minutes, while 3D cine-MR dynamics were acquired simultaneously (balanced turbo field echo). Each 3D dynamic spanned 9.4 seconds, and consisted of 448x448x45 voxels of 1.0x1.0x2.2mm. The prostate in all dynamics was automatically registered to INI and PV scans using a previously published method (D M de Muinck Keizer et al 2019 Phys. Med. Biol. 64 235008). In group 1, 24% of the patients required a VCS. In this group, intrafraction motion shifts relative to the treatment plan anatomy during dose delivery were 0.9±0.9 mm, 1.8±1.5 mm and 1.6±1.4 mm for respectively LR, AP and CC directions (mean ± SD of absolute values). In group 2, the VCS reduced the corresponding values to 0.4±0.4 mm, 1.4±1.2 mm and 1.3±1.3 mm. The average time between PV scan and beam on was 5 min, of which the VCS calculation time was below 1 min. An analysis of the required PTV margins in the corresponding directions showed that in group 2 margins could be safely reduced to 2, 4 and 4 mm in the LR, CC and AP directions. Daily VCS shortly before dose delivery allowed for a PTV margin reduction below conventionally applied 5 mm margins. However, due to the continuous and stochastical nature of intrafraction motion, margin reduction below 4 mm would require intrafraction plan adaptation. Presently, we develop such methods based on the high quality of the 1.5T 3D cineMR.

Predictors of Rectal Toxicity in Patients Receiving Prostate SBRT: The Effect of Intrafraction Rotation

Stereotactic Body Radiation Therapy (SBRT) is an emerging treatment option for men with localized prostate cancer. While the extent of prostate intrafraction translation and rotation has been previously investigated, the clinical impact of rotation independent of translation has not. Several series have characterized low rates of rectal toxicity when SBRT is used with different dose regimens. This study attempts to quantify the impact of intrafraction rotation on grade 2+ rectal toxicity for men diagnosed with prostate cancer treated with SBRT. Between April 11, 2006 and August 13, 2018, 1712 patients with prostate cancer were treated with robotic-based SBRT at an academic institution. 91.2% were treated with 3500cGy in 5 fractions while 8.8% received 3625cGy. 328 (19.7%) patients received ADT as a component of their treatment. By NCCN grouping, patients were treated for low risk (26.9%), intermediate risk (60.1%), and high risk (13.0%) disease. Each fraction employed real-time intrafraction translation correction. Due to prostate fiducial configuration or body habitus, 75 (4.4%) patients did not receive intrafraction rotation correction during treatment. Intrarectal amifostine was administered to patients prior to each SBRT fraction. Long-term rectal toxicity was scored by RTOG late toxicity scale. Freedom from grade 2+ proctitis was assessed using the Kaplan-Meier method and analyzed using Cox regression methods. 13 patients developed grade 2 proctitis while 7 developed the grade 3 endpoint. 0.41% of all patients required hyperbaric oxygen or procedural intervention to manage toxicity. With a mean follow-up of 29 months (6-148), the 5-year freedom from grade 2+ proctitis was 97.8%. Rectal bleeding was more likely for patients older than age 75 (7.4% vs. 2.0%, p=.003). In rare cases where intrafraction rotation was not corrected, a higher rate of patients experienced rectal bleeding (10.5% vs. 2.9%, p=.03). Dosimetrically, a rectal V3600cGy <3cc predicted for decreased risk of bleeding (2.6% vs. 7.8%, p=.006), as did Rectal V3400cGy<6cc’s (1.9% vs. 4.3%, p=.021). NCCN risk grouping, ADT, Race, and prescription dose (3500cGy vs. 3625cGy) were not significant. On multivariate analysis, the lone predictor of grade 2+ proctitis was intrafraction rotation non-correction (OR 4.033, CI 1.042-15.610, p=.043). SBRT for prostate cancer is well tolerated with a low actuarial risk of grade 2+ proctitis. Prostate rotation independent of translation has the potential to modestly affect rectal toxicity. In patients treated on robotic platforms with pre-treatment administration of amifostine, intrafraction translation and rotation correction minimizes long-term rates of rectal bleeding.

Dosimetric impact of intrafraction rotations in stereotactic prostate radiotherapy: A subset analysis of the TROG 15.01 SPARK trial

Background and purposeAccurate delivery of radiotherapy is critical to achieve optimal treatment outcomes. Interfraction translational IGRT is now standard, and intrafraction motion management is becoming accessible. Some platforms can report both translational and rotational movements in real time. This study aims to quantify the dosimetric impact of observed intrafraction rotation of the prostate measured using monitoring software. Materials and methodsA dose grid resampling algorithm was used to model the dosimetric impact of prostate rotations for 20 patients on a SBRT prostate clinical trial. Translations were corrected before and during treatment, but rotations were not. Real time rotation data were acquired using KIM and a cumulative histogram analysis performed. Prostate volumes were rotated by the range of observed angles and used to calculate DVH data. ResultsThe pitch axis had a higher range of observed rotations resulting in only 7 patients spending at least 90% of the beam on time across all fractions within rotation angles resulting in PTV D95% ≥36 Gy in this axis. The yaw and roll axes saw 17 and 15 patients respectively achieving this criterion. All but one of 20 patients exceeded CTV D98% ≥36 Gy for all observed rotation angles. ConclusionsCurrent CTV–PTV margins do not result in compromised CTV dose coverage due to inter and intrafraction prostate rotations in the absence of other uncertainties. Reduced PTV dosing is due to the extremely conformal treatment delivery but is unlikely to be clinically deleterious. Prostate standard IGRT should continue to focus on correcting any observed translational movements. Margin reduction could be explored in conjunction with other uncertainties.

Comparison of electromagnetic transmitter and ultrasound imaging for intrafraction monitoring of prostate radiotherapy

Background and purposeTo compare two in-beam monitoring devices for prostate radiotherapy: intra-prostatic electromagnetic transmitters (EM-T) (RayPilot®, Micropos Medical) and ultrasound imaging using transperineal probe (TP-US) (Clarity®, Elekta) used concomitantly on phantom and on patients. Materials and methodsThe phantom study evaluated accuracy in presence of known translations and rotations. Then intra-fraction motions were analyzed for 10 prostate cancer patients implanted with the EM-T 8 days before the simulation CT (171 sessions). The percent time in which the differences between the systems were 1–5 mm were scored for each direction. ResultsExperiments on phantom confirmed no interference between the systems and showed deviations of less than 0.5 mm when translations were applied progressively. In presence of rotations (5–15°), both systems displayed systematic shifts up to 6.9 and 3.8 mm for the TP-US and the EM-T, respectively. Absolute mean differences between displacements observed on patients with EM-T and TP-US were ≤0.55 mm in all directions except for one patient (≤1.77 mm). With an exception for this patient, a strong correlation was found in left–right direction: differences >2 mm were monitored less than 0.22% of the time (mean acquisition time:164 minutes) and never exceeded 5 s. Maximum differences were observed in supero-inferior direction with differences >2 mm monitored more than 6.5% of the time for 3 patients. Large prostate rotations, the presence of gas and EM-T location in the prostate may explain important differences. ConclusionApart from the systematic shifts induced by the rotations, the two systems were correlated and represent feasible solutions for monitoring prostate cancer treatment.

Hypofractionated Radiation Therapy Using Fiducial Markers: Assessment of Residual Error and Variation of Prostate Volume during Treatment

With the incorporation of fiducial markers as a surrogate for the prostate itself, the systematic and random positioning error can be removed from the treatment. However, geometric uncertainties remain with respect to the prostate’s position. In this study, two topics have been investigated: the residual error in the patient positioning associated to the rigid marker-based registration and the variation of the prostate volume during the treatment. A total of 375 pre-treatment CBCT images from 15 prostate cancer patients treated with a hypofractioned RT (2.7 Gy/session in 25 fractions) are included in the study. Two weeks before the treatment, all patients underwent the implantation of three gold seeds by ultrasound-guided insertion (one at the apex, S1, and two at each side of the prostate base, S2 left, S3 right). The positioning protocol consists of a daily CBCT acquisition followed by a rigid marker-based registration with the planning CT. The position coordinates of the markers and the isocenter are obtained from each study. In each treatment session, the prostate may undergo deformations that can lead to relative displacements between markers different from those of the CT simulation. This fact, together with the subjective alignment of the images, lead to an error associated to the registration. In order to quantify this potential error, the difference between the markers center of mass in the CBCT relative to the treatment isocenter and the center of mass in the CT relative to the planning isocenter was calculated. The residual errors from the combination of systematic and random errors were determined by quadratic addition. Additionally, markers distance variation per treatment session has been analyzed by deducing the separation distance two by two (D12, D13, D23) from markers coordinates. The results obtained for the residual error in the patient positioning are (mm): 0.7 lateral, 1.1 longitudinal, 1.3 vertical. The higher errors detected in the longitudinal and vertical directions could be explained by the prostate rotations on the left-right axis that are not completely compensated by the translational shifts. The distances between markers show a decrease during the treatment course. This fact is associated with a potential reduction in prostate volume. On average, it is observed that in session 12-13 the three distances begin to decrease in magnitude, with D23 showing a smaller reduction at the end of the treatment (about 1 mm). D12 and D13 decrease to 1.6 and 1.8 mm in the last session. The alignment of prostate cancer patients based on CBCT with fiducial markers entails a negligible residual error compared to the margins generally considered. The prostate shows a tendency to reduce its volume during treatment. This fact can have a relevant impact on treatment margins and on treatment re-planning strategies.

Prostate segmentation in MRI using a convolutional neural network architecture and training strategy based on statistical shape models.

Most of the existing convolutional neural network (CNN)-based medical image segmentation methods are based on methods that have originally been developed for segmentation of natural images. Therefore, they largely ignore the differences between the two domains, such as the smaller degree of variability in the shape and appearance of the target volume and the smaller amounts of training data in medical applications. We propose a CNN-based method for prostate segmentation in MRI that employs statistical shape models to address these issues. Our CNN predicts the location of the prostate center and the parameters of the shape model, which determine the position of prostate surface keypoints. To train such a large model for segmentation of 3D images using small data (1) we adopt a stage-wise training strategy by first training the network to predict the prostate center and subsequently adding modules for predicting the parameters of the shape model and prostate rotation, (2) we propose a data augmentation method whereby the training images and their prostate surface keypoints are deformed according to the displacements computed based on the shape model, and (3) we employ various regularization techniques. Our proposed method achieves a Dice score of 0.88, which is obtained by using both elastic-net and spectral dropout for regularization. Compared with a standard CNN-based method, our method shows significantly better segmentation performance on the prostate base and apex. Our experiments also show that data augmentation using the shape model significantly improves the segmentation results. Prior knowledge about the shape of the target organ can improve the performance of CNN-based segmentation methods, especially where image features are not sufficient for a precise segmentation. Statistical shape models can also be employed to synthesize additional training data that can ease the training of large CNNs.

Changes in prostate orientation due to removal of a Foley catheter.

Investigate the impact on prostate orientation caused by use and removal of a Foley catheter, and the dosimetric impact on men prospectively treated with prostate stereotactic body radiotherapy (SBRT). Twenty-two men underwent a CT simulation with a Foley in place (FCT), followed immediately by a second treatment planning simulation without the Foley (TPCT). The change in prostate orientation was determined by rigid registration of three implanted transponders between FCT and TPCT and compared to measured orientation changes during treatment. The impact on treatment planning and delivery was investigated by analyzing the measured rotations during treatment relative to both CT scans, and introducing rotations of ±15° in the treatment plan to determine the maximum impact of allowed rotations. Removing the Foley caused a statistically significant prostate rotation (P<0.0028) compared to normal biological motion in 60% of patients. The largest change in rotation due to removing a Foley occurs about the left-right axis (tilt) which has a standard deviation two to five times larger than changes in rotation about the Sup-Inf (roll) and Ant-Post (yaw) axes. The change in tilt due to removing a Foley for prone and supine patients was -1.1°±6.0° and 0.3°±7.4°, showing no strong directional bias. The average tilt during treatment was -1.6°±7.1° compared to the TPCT and would have been -2.0°±7.1° had the FCT been used as the reference. The TPCT was a better or equivalent representation of prostate tilt in 82% of patients, vs 50% had the FCT been used for treatment planning. However, 92.7% of fractions would still have been within the ±15° rotation limit if only the FCT were used for treatment planning. When rotated ±15°, urethra V105%= 38.85Gy <20% was exceeded in 27% of the instances, and prostate (CTV) coverage was maintained above D95% >37Gy in all but one instance. Removing a Foley catheter can cause large prostate rotations. There does not appear to be a clear dosimetric benefit to obtaining the CT scan with a Foley catheter to define the urethra given the changes in urethral position from removing the Foley catheter. If urethral sparing is desired without the use of a Foley, utilization of an MRI to define the urethra may be necessary, or a pseudo-urethral planning organ at risk volume (PRV) may be used to limit dosimetric hot spots.

Impact of rectal distension on prostate CBCT-based positioning assessed with 6 degrees-of-freedom couch

IntroductionProstate requires a daily correction of its 3-dimensional position in relation with rectal distension. In this study, we sought to determine whether rectal distension with respect to the rectal behavior might have an impact on prostate translations and/or rotations during prostate image guided radiation therapy using a 6 degrees-of-freedom (DOF) couch. Methods and materialsWe reviewed the data from 39 patients with localized prostate cancer treated with protracted external radiation therapy using a 6 DOF couch. Before each fraction, a kilovoltage cone beam computed tomography (kV-CBCT) scan was performed. The automatic fusion algorithm was set to fuse on soft tissue and allowed correction for translations in 3 dimensions and rotations in the longitudinal axis (“roll”) and lateral axis (“pitch”). After contouring the rectum on each kV-CBCT, we determined the cross-sectional area (CSA) and relative CSA (CSArel) by dividing with the CSA of planning CT. The standard deviation of CSArel per patient was used to classify the patients in 2 groups: patients with a stable rectum and patients with an unstable rectum. The CSArel was compared between these 2 groups with a linear mixed model with group as fixed effect and patient as random effect. ResultsA total of 616 kV-CBCT were analyzed, and 2 subgroups of patients could be defined a posteriori: 19 patients had a stable rectum, mean CSArel (1.06 ± 0.08); the other 20 patients had an unstable rectum, mean CSArel (1.43 ± 0.08). The average pitch in the group with a stable rectum was 0.36° (±0.21) versus 0.40° (±0.20) (P = .898). The pitch was not correlated with the CSArel (P = -.065, r = 0.119). The average roll in the group with a stable rectum was 0.27° (±0.16) versus 0.05° (±0.16) (P = .137). The roll was not correlated with the CSA (P = .094, r = 0.068). The average CSArel was higher (P = .0013) and more variable (P = .035) in the unstable group. ConclusionRectal distension had no impact on the pitch or on the roll, which suggest that a 6 DOF couch has little interest in daily practice for prostate image guided radiation therapy.

Multicomponent Assessment of the Geometrical Uncertainty and Consequent Margins in Prostate Cancer Radiotherapy Treatment Using Fiducial Markers

The aim is to compute all sources of geometrical uncertainty in prostate radiotherapy using fiducial markers and determine the safety treatment margins. Based on the markers position, correlations between prostate rotation/deformation and rectal and bladder fillings as well as changes in prostate volume during the treatment course are analyzed. The study includes 375 pre-treatment CBCT images from 15 prostate cancer patients treated with hypofractionated radiotherapy. The position coordinates of the markers were obtained from each image acquisition. In addition, rectum and bladder were outlined on CBCTs. The intrafractional error was estimated by an additional post-treatment CBCT acquired on alternate days. Tau-Kendall analysis was performed to correlate organ fillings with prostate rotation/deformation. Delineation uncertainty was assessed from contours of 10 patients performed by two radiation oncologists and repeated twice. The CT contouring was assisted by a multiparametric MR approach combining a T2-weighted with diffusion-weighted imaging, and a gradient recalled echo for fiducial marker identification. Uncertainty associated to treatment unit was estimated from phantom measurements. The obtained clinical margins were 4.4, 7.3, 5.1 mm in the Left-Right, Superior-Inferior, and Anterior-Posterior directions, respectively, being the contouring the most important contribution. The mechanical limitations of the beam delivery system and the associated imaging device entailed errors of the same order as prostate motion, rotation or deformation. Weak correlations between variation of the rectal volume and the presence of rotations/deformations were found (correlation coefficient 0.182, p = 0.001 for rotations around lateral axis; correlation coefficients 0.1, p < 0.05 for deformations). The distance between markers decreased with session number, becoming more pronounced from fraction 13 and reaching 1 - 1.8 mm at the end of the treatment. In summary we have determined the optimal treatment margins based on geometrical uncertainty assessment using van Herk formalism. An appropriate preparation of rectum and bladder involves minimizing the effect of prostate rotations/deformations. The prostate tends to decrease in size during the treatment which could influence treatment re-planning strategies.

8. Monitoring of prostate cancer with a transperineal ultrasound probe: Impact on treatment margins

Introduction To achieve a better accuracy in dose delivering in prostate cancer treatment a real-time prostate monitoring system for correcting interand intrafraction motion, such as the intramodality transperineal ultrasound device (TP-US) (Clarity®, Elekta, Sweden) is required. Previous studies had shown a good correlation between Cone beam CT (CBCT) without fiducial markers (FM) and TP-US [1] . However important differences remained in the antero-posterior direction (shift agreement at 5 mm: 82.6%) probably because of the low soft-tissue contrast of CBCT acquisitions. The first goal of this study was to compare pre-treatment registration results obtained with CBCT imaging with FM (CBCT + FM) to TP-US for prostate cancer treatment. Finally treatment margins were calculated for 4 treatment protocols: CT/CBCT + FM (1), CT/CBCT + FM followed by intra-fraction monitoring (IFM) (2), TP-US/TP-US + IFM (3) and TP-US/TP-US registration corrected by CT/CBCT + FM for the first 5 sessions + IFM (4). Methods 16 prostate patients were involved in this study. Pre-treatment positioning was first performed with TP-US/TP-US registration then corrected by CT/CBCT + FM registration as it was considered as the “gold standard”. The shifts detected during CBCT imaging and treatment were collected. After 5 sessions the mean of the differences between CBCT + FM and TP-US was calculated and applied to subsequent TP-US registrations to correct for the systematic differences observed between the 2 modalities. The differences between TP-US/TP-US and CBCT/CT registrations were analyzed on 255 sessions. Finally treatment margins considering inter-fraction motion, IFM and inter-operator variability as sources of uncertainties were calculated using van Herk formula [2] . Results CBCT + FM and TP-US shift agreements at ±5 mm were 91.8%, 92.2%, 95.3% in the left-right (LR), anterior-posterior (AP) and superior-inferior (SI) direction, respectively. Treatment margins were smaller using CT/CBCT + FM as a reference modality for pretreatment registration ( Table 1 ). The main differences between CBCT and TP-US protocols came from the uncertainties of interfraction motion, which were not considered in CBCT protocols, as it was the “gold standard”. The use of the IFM (2) as well as correction of systematic shifts for TP-US registrations (4) enabled to considerably reduce margins compared to (1) and (3), respectively. Conclusions A strong correlation was found between TP-US and CBCT + FM registrations. The use of IFM enabled to considerably reduce treatment margins. Furthers investigations are in progress to assess the robustness of CBCT + FM registrations notably in case of prostate rotations.

Fast online replanning for interfraction rotation correction in prostate radiotherapy.

To enable fast online replanning for prostate radiotherapy with the inclusion of interfraction rotations and translations and investigate the possibility for margin reduction via this regime. Online daily replanning for a 35-fraction treatment for five prostate cases is simulated while accounting for anatomical transformations derived from fiducial marker data available in our clinic. Two online replanning strategies were simulated, compensating for: (a) rotation-only in combination with a couch shift and (b) both translation and rotation without a couch shift. They were compared against our current clinical protocol consisting of a single offline plan used over all fractions with daily couch repositioning (translations only). For every patient, the above methods were generated for several planning margins (0-8 mm with 2 mm increments) in order to assess the performance of online replanning in terms of target coverage and investigate the possible dosimetric benefit for the organs at risk. The daily DVHs for each treatment strategy were used for evaluation and the non tumor integral dose (NTID) for the different margins was calculated in order to quantify the overall reduction of the delivered energy to the patient. Our system is able to generate a daily automated prostate plan in less than 2 min. For every patient, the daily treatment plans produce similar dose distributions to the original approved plan (average CTV D99 relative difference: 0.2%). The inclusion of both shifts and rotations can be effectively compensated via replanning among all planning margins (average CTV D99 difference: 0.01 Gy between the two replanning regimes). Online replanning is able to maintain target coverage among all margins, while - as expected - the conventional treatment plan is increasingly affected by the interfraction rotations as the margins shrink (average CTV D99 decrease: 0.2 Gy at 8 mm to 2.9 Gy at 0 mm margin). The possible gain in total delivered energy to the patient was quantified by the decreased NTID ranging from 12.6% at 6 mm to 32.9% at 0 mm. We demonstrate that fast daily replanning can be utilized to account for daily rotations and translations based on the daily positioning protocol. A daily plan can be generated from scratch in less than 2 min making it suitable for online application. Given the large magnitude of prostate rotation around the LR axis, online correction for daily rotations can be beneficial even for the clinical 8 mm margin and could be utilized for treatments with small margin reduction mainly limited then by anatomical deformations and intrafraction motion. Our online replanning pipeline can be used in future treatments with online MR guidance that can lead to further safe reduction of the planning margins.

A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

Initial experience with intra-fraction motion monitoring using Calypso guided volumetric modulated arc therapy for definitive prostate cancer treatment.

IntroductionAccurate delivery of radiation while reducing dose to organs at risk is essential in prostate treatment. The Calypso motion management system detects and corrects both inter‐ and intra‐fraction motion which offers potential benefits over standard alignment to fiducial markers. The aims of this study were to implement Calypso with Dynamic Edge™ gating and to assess both the motion seen, and interventions required.MethodsAn implementation group was formed which assessed changes needed to standard workflows. Three patients had Calypso beacons inserted into their prostate. All patients were treated using volumetric modulated arc therapy to a dose of 80 Gy in 40 fractions. Standard inter‐fraction motion correction using either kilovoltage (kV) orthogonal paired imaging or cone beam computed tomography (CBCT) image‐guided radiotherapy techniques, were used along with the Calypso system to compare accuracy. A gating threshold of >0.5 cm was used during treatment. Workflow variations along with inter‐ and intra‐fraction motion and interventions required were assessed.ResultsA total of 116 fractions were treated using Calypso with Dynamic Edge™ gating. There was a strong concordance between aligning beacons using kV orthogonal imaging or CBCT and Calypso (mean variation ≤0.06 cm). The mean intra‐fraction motion detected was ≤0.2 cm in all directions with the largest motion recorded being 2.2 cm in the left direction while the treatment beam was off. Prostate rotation was largest in the pitch direction and 28 fractions exceeded the 10° tolerance. A total of 78 couch shift corrections of ≥0.3 cm were required, usually following standard imaging, and before treatment starting. Three gating events due to intra‐fraction motion occurred during treatment.ConclusionsIntra‐fraction motion monitoring with Calypso was successfully implemented. Greatest movement was seen between time of standard imaging and treatment starting with more than half the treatments requiring a ≥0.3 cm adjustment. This would not have been detected without intra‐fraction monitoring.

Geographical miss of the prostate during image-guided radiotherapy with a 6-mm posterior expansion margin

IntroductionOur department commonly uses a planning target volume (PTV) expansion of 6 mm posterior and 1 cm in all other directions when treating prostate cancer patients with image‐guided radiotherapy (IGRT). This study aimed to test the adequacy of this PTV expansion by assessing geographical miss of the prostate on post‐treatment cone‐beam CT (CBCT) and identify those at risk of geographical miss.MethodsTwenty‐two prostate cancer patients receiving IGRT with implanted fiducial markers underwent daily pre‐treatment orthogonal kV imaging followed by a post‐treatment CBCT for a total of 432 fractions. The prostate was outlined on all CBCTs. For each imaging set, the volume of geographic miss was measured by subtracting the PTV from the planning CT and prostate volume on the post‐treatment CBCT.ResultsThe prostate volume moved outside the PTV by >0.01 cc in 9% of fractions (39/432). This occurred in 13 (59%) of 22 patients. Large prostates >40 cc and >50 cc had significantly more geographical miss events (both P < 0.001). Changes in rectal filling appear to be responsible for prostate motion/deformation in 82% (32/39) of fractions.ConclusionsOur analysis suggests that, despite IGRT, prostate PTV margins are not adequate in some patients, particularly those with large prostates. PTV margins may be reduced in some other patients. Prostate rotation and deformation play an important role in setting margins and may not always be represented accurately by fiducial marker displacements. Individualised and adaptive margins for prostate cancer patients should be a priority for future research.