Prostate Image-guided Radiotherapy Research Articles

UroLift implants as surrogate fiducial markers for cone-beam CT-based prostate image-guided radiotherapy

Abstract Introduction: UroLift implants are a novel treatment for the obstructive lower urinary tract symptoms arising from benign prostatic hyperplasia. This case study aimed to assess their effectiveness as fiducial marker (FM) surrogates in prostate image-guided radiotherapy (IGRT). Method: Cone-beam CT images from a patient receiving prostate radiation therapy underwent manual alignment using UroLift implants and also prostate soft-tissue matching by five experienced therapeutic radiographers. The match values of both methods were compared using Bland–Altman analysis. All five observers were also asked to score the ease of matching using both approaches. Results: The 95% mean level of agreement for the UroLift matches were within a 2-mm threshold in all dimensions. Comparison of UroLift and prostate matches had 95% limit of agreement values of −0·98 to 1·78, −0·58 to 0·49 and −1·83 to 1·04 mm in the vertical, longitudinal and lateral planes, respectively. All of the UroLift matches were rated as ‘very easy’ or ‘possible with little difficulty’ by the five observers. Conclusion: A small difference between the CBCT UroLift and CBCT prostate match was found. It has been shown that IGRT to the prostate with the aid of the UroLift system implants and CBCT is feasible and can eliminate the need for FM implants. Wider evaluation in a large cohort is recommended.

51: Patient’s Reported Outcomes (PROS) of an Ultra-Hypo Fractionated (UHF) Prostate Image Guided Radiation Therapy (IGRT) with Hdr Brachytherapy Boost (BB) as Compared to a Moderate Hypo Fractionated (MHF) Approach: Interim Analysis of a Phase Two Study

51: Patient’s Reported Outcomes (PROS) of an Ultra-Hypo Fractionated (UHF) Prostate Image Guided Radiation Therapy (IGRT) with Hdr Brachytherapy Boost (BB) as Compared to a Moderate Hypo Fractionated (MHF) Approach: Interim Analysis of a Phase Two Study

Spatial and dosimetric evaluation of residual distortions of prostate and seminal vesicle bed after image-guided definitive and postoperative radiotherapy of prostate cancer with endorectal balloon.

PurposeTo quantify daily residual deviations from the planned geometry after image‐guided prostate radiotherapy with endorectal balloon and to evaluate their effect on the delivered dose distribution.MethodsDaily kV‐CBCT imaging was used for online setup‐correction in six degrees of freedom (6‐dof) for 24 patients receiving definitive (12 RTdef patients) or postoperative (12 RTpostop patients) radiotherapy with endorectal balloon (overall 739 CBCTs). Residual deviations were evaluated using several spatial and dosimetric variables, including: (a) posterior Hausdorff distance HDpost (=maximum distance between planned and daily CTV contour), (b) point Pworst with largest HDpost over all fractions, (c) equivalent uniform dose using a cell survival model (EUDSF) and the generalized EUD concept (gEUDa with parameter a = −7 and a = −20). EUD values were determined for planned (EUDSFplan), daily (EUDSFind), and delivered dose distributions (EUDSFaccum) for plans with 6 mm (=clinical plans) and 2 mm CTV‐to‐PTV margin. Time series analyses of interfractional spatial and dosimetric deviations were conducted.ResultsLarge HDpost values ≥ 12.5 mm (≥15 mm) were observed in 20/739 (5/739) fractions distributed across 7 (3) patients. Points Pworst were predominantly located at the posterior CTV boundary in the seminal vesicle region (16/24 patients, 6/7 patients with HDpost ≥ 12.5 mm). Time series analyses revealed a stationary white noise characteristic of HDpost and relative dose at Pworst. The EUDSF difference between planned and accumulated dose distributions was < 5.4% for all 6‐mm plans. Evaluating 2‐mm plans, EUDSF deteriorated by < 10% (<5%) in 75% (58.5%) of the patients. EUDSFaccum was well described by the median value of the EUDSFind distribution. PTV margin calculation at Pworst yielded 8.8 mm.ConclusionsAccumulated dose distributions in prostate radiotherapy with endorectal balloon are forgiving of considerable residual distortions after 6‐dof patient setup if they are observed in a minority of fractions and the median value of EUDSFind determined per fraction stays within 95% of prescribed dose. Common PTV margin calculations are overly conservative because after online correction of translational and rotational errors only residual deformations need to be included. These results provide guidelines regarding online navigation, margin optimization, and treatment adaptation strategies.

Patient-based low dose cone beam CT acquisition settings for prostate image-guided radiotherapy treatments on a Varian TrueBeam linear accelerator.

To evaluate the performance of low dose cone beam CT (CBCT) acquisition protocols for image-guided radiotherapy of prostate cancer. CBCT images of patients undergoing prostate cancer radiotherapy were acquired with the settings currently used in our department and two low dose settings at 50% and 63% lower exposure. Four experienced radiation oncologists and two radiation therapy technologists graded the images on five image quality characteristics. The scores were analysed through Visual Grading Regression, using the acquisition settings and the patient size as covariates. The low dose acquisition settings have no impact on the image quality for patients with body profile length at hip level below 100 cm. A reduction of about 60% of the dose is feasible for patients with size below 100 cm. The visibility of low contrast features can be compromised if using the low dose acquisition settings for patients with hip size above 100 cm. Low dose CBCT acquisition protocols for the pelvis, based on subjective evaluation of patient images.

Current status of intensity-modulated radiation therapy for prostate cancer: History, clinical results and future directions.

External beam radiotherapy has changed dramatically over several decades with the improvement of computer hardware and software, and machinery developments. Intensity-modulated radiation therapy is the most sophisticated technique for all cancer treatment with radiation therapy, and is widely disseminated and available for daily use in many countries. Several retrospective and prospective studies have shown that intensity-modulated radiation therapy reduces the radiation dose in the organs at risk with diminished rates of acute and late toxicity, even with higher doses (>74Gy). An important technique for the clinical use of intensity-modulated radiation therapy is image-guided radiation therapy. The clinical benefit for prostate image-guided radiation therapy has been assessed by comparing the outcomes of patients with either the image-guided radiation therapy or non-image-guided radiation therapy technique. These studies have shown that image-guided radiation therapy significantly decreases acute and late rectal and bladder toxicities. Randomized trials and meta-analysis have shown that higher doses result in better biochemical control. More recently, hypofractionated radiation therapy comparing hypofractionated radiation therapy versus conventional fractionated radiation therapy have shown that hypofractionated radiation therapy produces biochemical control and toxicity rated similar to those produced by conventional fractionated radiation therapy. The clinical use of ultrahypofractionated radiation therapy and simultaneous integrated boost technique is necessary to evaluate its further safety and benefits. Intensity-modulated radiation therapy is also widely accepted in the field of salvage therapy and for the patients with distant oligometastases. The purpose of the present review is to summarize the history of intensity-modulated radiation therapy, new techniques for intensity-modulated radiation therapy, hypofractionation and future directions for prostate cancer.

Observed high incidence of prostatic calculi with the potential to act as natural fiducials for prostate image guided radiotherapy

This study aims to quantify the incidence and distribution of prostatic calculi in a population of prostate radiotherapy patients and assess their potential role in prostate image guided radiotherapy (IGRT). A retrospective analysis of trans-rectal ultrasound (TRUS), computed tomography (CT) planning and treatment verification cone beam CT (CBCT) scans from radical prostate radiotherapy patients (external beam and brachytherapy) between 2012 and 2014 was undertaken by a single experienced observer. An internationally validated schema from the Prostate Imaging Reporting and Data system (PIRADS) was used to map the location of calculi. The association of calculi with patient and disease characteristics was explored. Data was analysed using SPSS (IBM version 22.0) using descriptive statistical methods and logistic binary regression analysis. 389 scan sets from 254 patients were included in the analysis. The overall incidence of calculi was 85% (n = 218) of which 79% (n = 201) were intra-prostatic calculi. The mean number of intra-prostatic calculi was 2 (range 1-10) and the mean size of calculi was 3.7 mm (range 0.5-15 mm). Calculi were most frequently observed in the posterior of the mid-gland (PI-RADs 3p, 9p) and posterior of the apex (PI-RADs 5p, 11p). 99% (n = 135) of CT planning scans with a corresponding CBCT had calculi in the same PIRADs location and all calculi were visible at the last fraction. There was no statistically significant association of calculi and N stage, M stage or Gleason score. A significant proportion of prostate radiotherapy patients have prostatic calculi detectable on pre radiotherapy imaging. Calculi observed on CT were also detectable on CBCT in 99% of cases and remain visible at the end of treatment. These findings add to the growing evidence base supporting the potential of calculi as an alternative to fiducial markers to aid prostate IGRT.

Image-guided prostate radiotherapy: analysis of inter- fractional setup errors

Introduction: The accuracy of the patient setup and tumor location are major factors that determine the efficacy of radiotherapy treatment planning. In the prostate radiotherapy, reproducibility of the prostate location for each treatment fraction is problematic owing to varying filling of the rectum and bladder. According to this, the aim of this study was to measure the inter- fractional setup errors using gold markers implanted into the prostate and electronic portal imaging device (EPID). The results were used to determine optimal CTV-PTV (clinical target volume-planning target volume) margin. Materials and Methods: Image-guided three-dimensional conformal radiotherapy (3DCRT) was performed by daily online verification of implanted fiducial prostate markers using a megavoltage EPID. In this retrospective study, a total of 359 image-guided treatment fractions from 15 prostate cancer patients were analyzed. PTV was defined as an isotropic margin of 5 mm around of CTV. Daily electronic portal images (EPIs) compared to reference digitally reconstructed radiographs (DRRs), the setup errors were determined and online corrections applied. Mean displacements, population systematic and random errors were calculated. CTV-PTV margin was determined using van Herk’s formula. Results: The mean shifts in the vertical, longitudinal and lateral directions were 0.31 mm, 0.22 mm and – 0.41 mm, respectively. The population systematic and random errors in the three mentioned translational directions were 0.70 mm, 0.80 mm and 1.00 mm and 2.11 mm, 2.24 mm and 2.20 mm, correspondingly. CTV-PTV margin of 3.23 mm, 3.60 mm and 4.04 mm in the vertical, longitudinal and lateral directions were calculated. Conclusion: The calculated PTV margin was less than 5 mm, therefore PTV margin applied in this study provides a sufficient PTV coverage. Daily EPIs combined with gold markers implanted into the prostate provide an effective tool for verifying of the prostate position immediately prior to treatment delivery.

208. Investigation on target motion with intraprostatic fiducial markers and daily CBCT in radical radiotherapy for prostate cancer

Purpose Nowadays there is a great interest on the improvement of the patient setup variability and target motion in radical radiotherapy for prostate cancer thanks to the fiducial markers inside the target [1] . The prostate lies in proximity to hollow organs (bladder and rectum) which are at risk of toxicity and may be displaced due to filling of these organs. To assess the utility of this method, we evaluated setup and target motion errors with daily fiducial-based CBCT in prostate image-guided radiotherapy; the radio-opaque seeds makes possible to monitor the previous discussed soft tissue structures. Methods Ten patients with prostate adenocarcinoma at intermediate-risk underwent radical radiotherapy with RapidArc technique and daily CBCT. They were previously subjected to intra-prostatic radio-opaque fiducial markers implantation. PTV included prostate and seminal vesicles. Patients were aligned to the treatment isocenter by laser. During treatment, daily CBCT were acquired and a matching according to fiducials was performed. After that, coach shifts required for isocenter correction were carried out. We measured lateral-lateral (LL), anterior-posterior (AP) and cranial-caudal (CC) shift adjustments. Results Mean and Standard Deviation of shifts in longitudinal, vertical and lateral directions signed in daily CBCT-matching according to fiducial markers for each patient were estimated as reported in Fig. 1. As a preliminary result, lateral shift mean is higher than the other two, whereas longitudinal and vertical shifts are affected by higher standard deviation. It could be due to the inter-fraction morphologic variations of patients. Conclusions The correct reproducibility of prostate treatment is affected by setup error and organ motion. Daily IGRT with fiducial-based CBCT ensures accuracy of the treatment since it is able to track the target position, mainly in the modern radiotherapy techniques with dose escalation to the target. Download : Download high-res image (215KB) Download : Download full-size image

Fiducial markers implantation for prostate image-guided radiotherapy: a report on the transperineal approach.

In the external beam prostate cancer radiation therapy, daily gland displacement could lead to a target missing. The use of intra-prostatic gold fiducial markers for daily prostate position verification and correction before and during treatment delivery (image-guided radiotherapy, IGRT) is widely used in the radiation therapy centers to accurately target the prostate. Usually, the fiducial markers are implanted through the rectum, with complications such as infections and rectal bleeding. We report our experience in prostate fiducial markers implantation through a transperineal approach. Between September 2011 and January 2018 at our center, 101 patients underwent gold seed fiducial marker transperineal ultrasound-guided implantation for prostate IGRT. We retrospectively reviewed their features and outcome. Twenty-two (21.8%) patients had previously been subjected to a transurethral prostate resection (TURP) for obstructive urinary symptoms because of benign prostatic hypertrophy. No antibiotic prophylaxis was used. The procedure was well tolerated. In one patient, a single episode of self-limiting urinary bleeding occurred just after it. No other complication was recorded. All the patients, at the evaluation before discharge, reported no pain or dysuria. No rectal bleeding, hematospermia, urinary obstruction or infection were reported in the next days. No markers lost or migration occurred. According to our experience, prostate fiducial markers implantation through a transperineal approach is safe and should be recommended to limit the use of antibiotic therapy and patients morbidity. A previous TURP was not related to a higher risk of loss of seeds.

Visualizing the Invisible in Prostate Radiation Therapy: Markerless Prostate Target Localization Via a Deep Learning Model and Monoscopic Kv Projection X-Ray Image

Current image guided prostate radiotherapy often relies on the use of implanted fiducial markers (FMs) or transducers for online/offline target localization. Fiducial or transducer insertion requires an invasive procedure that adds cost and risks for bleeding, infection and discomfort to the patient. We are developing a novel markerless prostate localization strategy using a pre-trained deep learning model to interpret routine projection kV X-ray images without the need for daily cone-beam computed tomography (CBCT). We trained a deep learning model to recognize prostate treatment target location from over 800 annotated projection X-ray images using data augmentation to enhance the learning process. The end point of the deep learning was a model capable of identifying the location of the prostate target for a given input X-ray projection image. To assess the accuracy of the approach, we retrospectively studied images from four patients who received volumetric modulated arc therapy (VMAT)for prostate cancer. In each case, the daily patient setup anterior-posterior (AP) and lateral images were used as the input for analysis by our deep learning model to derive the prostate target location. We quantitatively compared the results obtained from the deep learning model with the annotations. A comparison of the results with that defined by fiducial localization and with location derived from the on-board CBCT imaging was also done. Training the deep learning model took about one hour for each view angle. After training, the model identified the prostate location on a projection kV image within 200 ms. The deviations between the target positions obtained by the deep learning model and the corresponding annotations ranged from 0.7 mm to 2.21 mm for AP direction, and from 1.23 mm to 2.20 mm for lateral direction. Oblique images may be useful for online tracking. The deviations for images obtained at oblique angles ranged from 0.67 mm to 2.88 mm. Target position provided by deep learning model for the kV images acquired using OBI is found to be consistent that derived from the implanted FMs. This study demonstrates that highly accurate markerless prostate localization based on deep learning is achievable. The strategy provides a clinically valuable solution for image guided radiotherapy of the prostate and should be adaptable to other soft tissue tumor targets. The proposed method may be useful for daily patient positioning and real-time target tracking during prostate radiotherapy.

Daily Versus Weekly Prostate Cancer Image Guided Radiation Therapy: Phase 3 Multicenter Randomized Trial

The optimal frequency of prostate cancer image guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. This phase 3 randomized trial recruited patients with N0 localized prostate cancer. The total IGRT doses in the prostate ranged from 70Gy to 80Gy, sparing the lymph nodes. Patients were randomly assigned (1:1) to 2 prostate IGRT frequency groups: daily and weekly (ie, on days 1, 2, and 3 and then weekly). The primary outcome was 5-year recurrence-free survival. Secondary outcomes included overall survival and toxicity. Post hoc analyses included biochemical progression-free interval, clinical progression-free interval, and other cancer-free interval. Between June 2007 and November 2012, 470 men from 21 centers were randomized into the 2 groups. Median follow-up was 4.1years. There was no statistically significant difference in recurrence-free survival between the groups (hazard ratio [HR]=0.81; P=.330). Overall survival was worse in the daily group than in the weekly group (HR=2.12 [95% confidence interval (CI), 1.03-4.37]; P=.042). Acute rectal bleeding (grade ≥1) was significantly lower in the daily group (6%) (n = 14) than in the weekly group (11%) (n = 26) (P=.014). Late rectal toxicity (grade ≥1) was significantly lower in the daily group (HR=0.71 [95% CI, 0.53-0.96]; P=.027). Biochemical progression-free interval (HR=0.45 [95% CI, 0.25 - 0.80]; P=.007) and clinical progression-free interval (HR=0.50 [95% CI, 0.24-1.02]; P=.057) were better in the daily group, whereas other cancer-free interval was worse in the daily group (HR=2.21 [95% CI, 1.10-4.44]; P=.026). Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity.

A feature alignment score for online cone-beam CT-based image-guided radiotherapy for prostate cancer.

To develop a method for scoring online cone-beam CT (CBCT)-to-planning CT image feature alignment to inform prostate image-guided radiotherapy (IGRT) decision-making. The feasibility of incorporating volume variation metric thresholds predictive of delivering planned dose into weighted functions, was investigated. Radiation therapists and radiation oncologists participated in workshops where they reviewed prostate CBCT-IGRT case examples and completed a paper-based survey of image feature matching practices. For 36 prostate cancer patients, one daily CBCT was retrospectively contoured then registered with their plan to simulate delivered dose if (a) no online setup corrections and (b) online image alignment and setup corrections, were performed. Survey results were used to select variables for inclusion in classification and regression tree (CART) and boosted regression trees (BRT) modeling of volume variation metric thresholds predictive of delivering planned dose to the prostate, proximal seminal vesicles (PSV), bladder, and rectum. Weighted functions incorporating the CART and BRT results were used to calculate a score of individual tumor and organ at risk image feature alignment (FASTV_OAR ). Scaled and weighted FASTV_OAR were then used to calculate a score of overall treatment compliance (FASglobal ) for a given CBCT-planning CT registration. The FASTV_OAR were assessed for sensitivity, specificity, and predictive power. FASglobal thresholds indicative of high, medium, or low overall treatment plan compliance were determined using coefficients from multiple linear regression analysis. Thirty-two participants completed the prostate CBCT-IGRT survey. While responses demonstrated consensus of practice for preferential ranking of planning CT and CBCT match features in the presence of deformation and rotation, variation existed in the specified thresholds for observed volume differences requiring patient repositioning or repeat bladder and bowel preparation. The CART and BRT modeling indicated that for a given registration, a Dice similarity coefficient >0.80 and >0.60 for the prostate and PSV, respectively, and a maximum Hausdorff distance <8.0 mm for both structures were predictive of delivered dose ± 5% of planned dose. A normalized volume difference <1.0 and a CBCT anterior rectum wall >1.0 mm anterior to the planning CT anterior rectum wall were predictive of delivered dose >5% of planned rectum dose. A normalized volume difference <0.88, and a CBCT bladder wall >13.5 mm inferior and >5.0 mm posterior to the planning CT bladder were predictive of delivered dose >5% of planned bladder dose. A FASTV_OAR >0 is indicative of delivery of planned dose. For calculated FASTV_OAR for the prostate, PSV, bladder, and rectum using test data, sensitivity was 0.56, 0.75, 0.89, and 1.00, respectively; specificity 0.90, 0.94, 0.59, and 1.00, respectively; positive predictive power 0.90, 0.86, 0.53, and 1.00, respectively; and negative predictive power 0.56, 0.89, 0.91, and 1.00, respectively. Thresholds for the calculated FASglobal of were low <60, medium 60-80, and high >80, with a 27% misclassification rate for the test data. A FASglobal incorporating nested FASTV_OAR and volume variation metric thresholds predictive of treatment plan compliance was developed, offering an alternative to pretreatment dose calculations to assess treatment delivery accuracy.

The potential failure risk of the cone-beam computed tomography-based planning target volume margin definition for prostate image-guided radiotherapy based on a prospective single-institutional hybrid analysis

BackgroundThe purpose of this study was to evaluate the impact of markerless on-board kilovoltage (kV) cone-beam computed tomography (CBCT)-based positioning uncertainty on determination of the planning target volume (PTV) margin by comparison with kV on-board imaging (OBI) with gold fiducial markers (FMs), and to validate a methodology for the evaluation of PTV margins for markerless kV-CBCT in prostate image-guided radiotherapy (IGRT).MethodsA total of 1177 pre- and 1177 post-treatment kV-OBI and 1177 pre- and 206 post-treatment kV-CBCT images were analyzed in 25 patients who received prostate IGRT with daily localization by implanted FMs. Intrafractional motion of the prostate was evaluated between each pre- and post-treatment image with these two different techniques. The differences in prostate deviations and intrafractional motions between matching by FM in kV-OBI (OBI-FM) and matching by soft tissues in kV-CBCT (CBCT-ST) were compared by Bland-Altman limits of agreement. Compensated PTV margins were determined and compensated by references.ResultsMean differences between OBI-FM and CBCT-ST in the anterior to posterior (AP), superior to inferior (SI), and left to right (LR) directions were − 0.43 ± 1.45, − 0.09 ± 1.65, and − 0.12 ± 0.80 mm, respectively, with R2 = 0.85, 0.88, and 0.83, respectively. Intrafractional motions obtained from CBCT-ST were 0.00 ± 1.46, 0.02 ± 1.49, and 0.15 ± 0.64 mm, respectively, which were smaller than the results from OBI-FM, with 0.43 ± 1.90, 0.12 ± 1.98, and 0.26 ± 0.80 mm, respectively, with R2 = 0.42, 0.33, and 0.16, respectively. Bland-Altman analysis showed a significant proportional bias. PTV margins of 1.5 mm, 1.4 mm, and 0.9 mm for CBCT-ST were calculated from the values of CBCT-ST, which were also smaller than the values of 3.15 mm, 3.66 mm, and 1.60 mm from OBI-FM. The practical PTV margin for CBCT-ST was compensated with the values from OBI-FM as 4.1 mm, 4.8 mm, and 2.2 mm.ConclusionsPTV margins calculated from CBCT-ST might be underestimated compared to the true PTV margins. To determine a reliable CBCT-ST-based PTV margin, at least the systemic error Σ and the random error σ for on-line matching errors need to be investigated by supportive preliminary FM evaluation at least once.

Characterization of a novel liquid fiducial marker for multimodal image guidance in stereotactic body radiotherapy of prostate cancer.

Liquid fiducial markers have shown to be a promising alternative to solid gold markers in terms of imaging artifact reduction, patient comfort, and compatibility with different imaging modalities. This study aims to investigate the performance of the novel BioXmark® liquid marker for state-of-the-art multimodal imaging used in prostate cancer (PCa) radiotherapy, encompassing kV CT/CBCT, multiparametric MRI, and kV x-ray imaging. In addition, automatic detection of the liquid markers in x-ray imaging for prostate motion monitoring during treatment was investigated. A total of eight BioXmark® liquid markers with varying volumes (range 5-300 μL) were casted on a square grid into a gelatin phantom insert. A cylindrical gold marker (QLRAD, length = 7 mm, Ø = 1 mm) was inserted for reference. Liquid marker visibility and streaking artifacts in CT/CBCT imaging were evaluated by placing the gelatin phantom into a CIRS anthropomorphic phantom. Relevant MRI characteristics such as the T2 and T1 relaxation times, the ADC value, and the relative proton density (ρH) were quantified by placing the gelatin phantom insert next to a T1MES mapping phantom and a water-filled syringe for reference. Ex vivo multiparametric MRI images were acquired by placing the gelatin phantom next to a resected prostate specimen. Anterior-posterior x-ray projection images were obtained by placing the gelatin phantom insert on top of an anthropomorphic pelvic phantom with internal pelvic bony structures and were acquired for five positions relative to the bony anatomy and 24 clinically relevant x-ray exposure settings. To quantify individual automatic marker detection, single markers were artificially isolated in the x-ray images using postprocessing. Markers of all sizes were clearly visible on CT and CBCT images with only the largest marker volumes (100-300 μL) displaying artifacts similar in size to the gold fiducial marker. Artifact size increased with increasing liquid marker volume. Liquid markers displayed good contrast in ex vivo T1-weighted and ρH-weighted images. The markers were not visible in the ex vivo T2-weighted image. The liquid markers induced a chemical shift artifact in the obtained ADC-map. Automated detection in x-ray imaging was feasible with high detection success (four of five positions) for marker volumes in the range of 25-200 μL. None of the liquid markers were detected successfully when superimposed on a bony edge, independent of their size. This study is the first to show the compatibility of BioXmark® liquid markers with multimodal image-guided radiotherapy for PCa. Compared to a solid gold marker, they had favorable results in both visibility and induced imaging artifacts. Liquid marker visibility in MRI imaging of the prostate does not solely depend on the low ρH value (not visible on T2-weighted image) but is also influenced by its relaxation times. Automated marker detection in x-ray images was feasible but better adapted marker detection algorithms are necessary for marker localization in the presence of bony edges. Hence, the liquid marker provides a minimally invasive (fine needles) and highly applicable alternative to current solid gold markers for multimodal image-guided prostate radiotherapy treatments.

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.

CASPIR trial: Using prostatic calculi as an alternative to fiducial markers for IGRT in for localized prostate cancer.

60 Background: Image guided Radiotherapy (IGRT) for prostate cancer (PCA) frequently employs surgically implanted fiducial markers (FMs). However, it is estimated that up to 35% of prostate radiotherapy patients have prostatic calculi (PC) visible on treatment cone beam CTs (CBCT). The purpose of this clinical trial is to directly compare FMs with PCs as an aid to prostate IGRT. Methods: We report data from a single institution prospective clinical trial investigating the feasibility of using prostate calcifications as natural FMs for IGRT. Patients planned for standard prostate radical EBRT +/- brachytherapy were eligible. Prior to CT planning, 3 gold fiducial markers are inserted into the prostate by the trans-perineal route under TRUS guidance. PCs visible within the PTV were contoured. Participants were aligned to FMs for EBRT using daily CBCT image guidance on a Varian TrueBeam linac. Off-line, a single experienced user analyses CBCTs using Image Registration in Eclipse (version 13.6). Random and systematic set-up errors are determined based on FMs, PCs (where present), prostate gland (PG) and bony landmarks (BL) and CTV-PTV margins derived for each data set. Results: 30 participants with PC have been recruited. Data from the first 19 patients (365 fractions), resulted in 2555 individual image registrations (7665 individual data points). The PTV margins required based on each reference structure are summarised in Table 1. The maximum difference between the CTV-PTV(PC) margin and CTV-PTV(FM) margin is 2.2mm in the X or L/R dimension. Margins required for FM, PG and PC in the Y and Z dimensions are comparable, with a maximum difference of 0.5mm between CTV-PTV(PC) and CTV-PTV(PG). Conclusions: Preliminary results from this study demonstrate some evidence to support the use of PCs as an alternative to FMs for prostate IGRT. Future analysis will include location of PC according to the PIRADs schema and patient feedback in relation to FM implantation. Clinical trial information: NA. [Table: see text]

Daily versus weekly prostate cancer image-guided radiotherapy: A phase 3, multicenter, randomized trial.

4 Background: The optimal frequency of prostate cancer image-guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. Methods: This Phase III randomized trial recruited 470 patients with N0 localized prostate cancer, from 21 centers between June 2007 and November 2012. Total IGRT doses ranged from 70 to 80 Gy. Patients were randomly assigned (1:1) to two prostate IGRT control frequency groups: daily or weekly (Days 1, 2, and 3, then weekly). The primary outcome was 5-year recurrence-free survival (RFS). Secondary outcomes included overall survival (OS) and toxicity (CTCAE V.3.0). Post-hoc analyses included biochemical progression-free interval (BPFI), clinical progression-free interval (CPFI) and second cancer-free interval (SCFI). Results: Median follow-up was 4.1 years (Q1 – Q3 = 3.1 – 5.1).There was no statistically-significant difference in RFS between the groups (hazard ratio [HR] = 0.81 [95% CI: 0.52 – 1.25]; p = 0.330). OS was worse in the daily control group versus the weekly control group (HR = 2.12 [95% CI: 1.03 – 4.37]; p = 0.042). Late rectal toxicity (Grade ≥1) incidence was significantly lower in the daily control group (HR = 0.71 [95% CI: 0.53 – 0.96]; p = 0.027). BPFI was better in the daily control group versus the weekly control group (HR = 0.45 [95% CI: 0.25 – 0.80]; p = 0.007). CPFI was better in the daily control group (HR = 0.50 [95% CI: 0.24 – 1.02]; p = 0.057). SCFI was worse in the daily control group versus the weekly control group (HR = 2.21 [95% CI: 1.10 – 4.44]; p = 0.026). Conclusions: Compared to weekly control, daily IGRT control in prostate cancer significantly decreases the risks of recurrence and late rectal toxicity but is associated with an increased risk of second cancer. Clinical trial information: NCT00433706.

Auto-Contour Guided Prostate Patient Positioning

To use contours automatically generated on the pre-treatment cone-beam CT (CBCT) to improve the registration with the plan CT for prostate image-guided radiation therapy (IGRT). 10 patients, each with 10 to 28 daily kV-CBCTs, had their prostate manually contoured on the plan CT and daily CBCTs. Prostate contours were also automatically generated on the CBCTs. Auto-contours are produced by deformably registering prior CBCTs (atlases) to the current CBCT and deforming the prior contours with the resulting deformation field. This set of deformed prostate contours on the current CBCT is then combined using the STAPLE algorithm. The optimal IGRT shift is determined by comparing the centroid of the manual prostate contour in the CBCT and plan CT. This shift is compared both to the clinical shift that was based on qualitative alignment of the images, and to a centroid shift based on auto-contours. The dosimetric impact of the different shift methods is estimated by overlaying the plan prescription isodose line on the CBCT according to the shifts, and then determining the coverage of the manual prostate and PTV contours. On average there is a 2.3±1.5 mm difference in the superior/inferior (SI) direction between the clinical and centroid shifts. The difference is 0.9±0.7 mm in the left/right (LR) and 1.8±1.5 mm in the anterior/posterior (AP) directions. Using the clinical shifts gave on average 98.7±2.6% coverage of the prostate, and 89.6±3.8% coverage of the PTV by the prescription dose. Centroid based shifts gave significantly better coverage of 99.5±1.1% (P=0.0013) and 92.7±2.4% (P<0.00001) for the prostate and PTV respectively. The reduction in standard deviation also implies more consistent coverage day to day with the centroid shifts. The average dice similarity coefficient of prostate auto-contours to manual contours is 0.91, which equals our intra-observer error. The average time for auto-contouring was 90 seconds on a Tesla K20c GPU. Using auto-contours to determine the centroid produces equivalent shifts to the manual contour centroid shifts, with average differences of 0.8±0.6, 0.4±0.3 and 0.8±0.7 mm in SI, LR and AP directions, respectively. This is to be expected given the consistency of the manual and auto-contours. There are >2 mm differences between our new centroid based shifts and the current clinical, image based shifts, with centroid based shifts providing significantly higher prostate coverage. Auto-contouring provides equivalent shifts to manual centroid based shifts. IGRT can thus be fully automated, resulting in improved prostate coverage.

Intrafractional Tracking Accuracy of a Transperineal Ultrasound Image Guidance System for Prostate Radiotherapy.

Purpose:The aim of this study is to evaluate the tracking accuracy of a commercial ultrasound system under relevant treatment conditions and demonstrate its clinical utility for detecting significant treatment deviations arising from inadvertent intrafractional target motion.Methods:A multimodality male pelvic phantom was used to simulate prostate image-guided radiotherapy with the system under evaluation. Target motion was simulated by placing the phantom on a motion platform. The tracking accuracy of the ultrasound system was evaluated using an independent optical tracking system under the conditions of beam-on, beam-off, poor image quality with an acoustic shadow introduced, and different phantom motion cycles. The time delay between the ultrasound-detected and actual phantom motion was investigated. A clinical case example of prostate treatment is presented as a demonstration of the utility of the system in practice.Results:Time delay between the motion phantom and ultrasound tracking system is 223 ± 45.2 milliseconds including video and optical tracking system frame rates. The tracking accuracy and precision were better with a longer period. The precision of ultrasound tracking performance in the axial (superior–inferior) direction was better than that in the lateral (left–right) direction (root mean square errors are 0.18 and 0.25 mm, respectively). The accuracy of ultrasound tracking performance in the lateral direction was better than that in the axial direction (the mean position errors are 0.23 and 0.45 mm, respectively). Interference by radiation and image quality do not affect tracking ability significantly. Further, utilizing the tracking system as part of a clinical study for prostate treatment further verified the accuracy and clinical appropriateness.Conclusions:It is feasible to use transperineal ultrasound daily to monitor prostate motion during treatment. Our results verify the accuracy and precision of an ultrasound system under typical external beam treatment conditions and further demonstrate that the tracking system was able to identify important prostate shifts in a clinical case.

The dosimetric impact of manual adjustments following automated registration in prostate image-guided radiotherapy

AbstractAimAlthough manual adjustment of automatic cone beam computed tomography (CBCT) matching may improve the target coverage in certain points of interest, concerns exist that this may lead to dosimetric uncertainties which would negate the theoretical benefit of this approach. The objective of this study is to evaluate the dosimetric impact of manual adjustments made after automatic bony registration on CBCT in prostate patients.MethodsA total of 50 CBCT datasets of ten high-risk prostate cancer patients were randomly chosen. Each CBCT dataset was registered three times. Method (A): Automatic registration, Method (M1): Manual adjustment carried out by two experienced radiation therapists, Method (M2): Manual adjustment carried out by different radiation therapists with varying levels of experience. The clinical target volume (CTV), planning target volume (PTV), the bladder and the rectum were subsequently contoured on each CBCT dataset by a radiation oncologist blinded to the registration methods. The absolute difference of various dosimetric parameters were then analysed and compared with the original planning doses. A comparison of the three matching methods employed was also carried out.ResultsThere was a statistically significant difference in the magnitude of move taken in the inferior superior direction between M1 and M2 method. There were no significant differences observed in any of the dosimetric parameters examined in relation to the rectum, bladder or CTV. The only significant difference observed was the volume of PTV covered by the prescription isodose (95%) which was statistically significant lower in method A compared with both M1 and M2. There was no difference observed between M1 and M2 methods. The mean duration of the automated registration and subsequent analysis was 64 seconds compared with 91 seconds for automated registrations which included the additional manual adjustment.FindingsCBCT-based manual adjustments of automated bony-based registrations during the image-guided radiotherapy verification of prostate cancer patients can improve PTV coverage without impacting negatively on the doses received by the organs at risk. This strategy is associated with a small increase in overall treatment time.