A systematic review of assessment approaches to predict opioid misuse in people with cancer.

CONTEXT: Cancer prevalence is increasing, with many patients requiring opioid analgesia. Clinicians need to ensure patients receive adequate pain relief. However, opioid misuse is widespread, and cancer patients are at risk. OBJECTIVES: This study aims (1) to identify screening approaches that have been used to assess and monitor risk of opioid misuse in patients with cancer; (2) to compare the prevalence of risk estimated by each of these screening approaches; and (3) to compare risk factors among demographic and clinical variables associated with a positive screen on each of the approaches. METHODS: Medline, Cochrane Controlled Trial Register, PubMed, PsycINFO, and Embase databases were searched for articles reporting opioid misuse screening in cancer patients, along with handsearching the reference list of included articles. Bias was assessed using tools from the Joanna Briggs Suite. RESULTS: Eighteen studies met the eligibility criteria, evaluating seven approaches: Urine Drug Test (UDT) (n = 8); the Screener and Opioid Assessment for Patients with Pain (SOAPP) and two variants, Revised and Short Form (n = 6); the Cut-down, Annoyed, Guilty, Eye-opener (CAGE) tool and one variant, Adapted to Include Drugs (n = 6); the Opioid Risk Tool (ORT) (n = 4); Prescription Monitoring Program (PMP) (n = 3); the Screen for Opioid-Associated Aberrant Behavior Risk (SOABR) (n = 1); and structured/specialist interviews (n = 1). Eight studies compared two or more approaches. The rates of risk of opioid misuse in the studied populations ranged from 6 to 65%, acknowledging that estimates are likely to have varied partly because of how specific to opioids the screening approaches were and whether a single or multi-step approach was used. UDT prompted by an intervention or observation of aberrant opioid behaviors (AOB) were conclusive of actual opioid misuse found to be 6.5-24%. Younger age, found in 8/10 studies; personal or family history of anxiety or other mental ill health, found in 6/8 studies; and history of illicit drug use, found in 4/6 studies, showed an increased risk of misuse. CONCLUSIONS: Younger age, personal or familial mental health history, and history of illicit drug use consistently showed an increased risk of opioid misuse. Clinical suspicion of opioid misuse may be raised by data from PMP or any of the standardized list of AOBs. Clinicians may use SOAPP-R, CAGE-AID, or ORT to screen for increased risk and may use UDT to confirm suspicion of opioid misuse or monitor adherence. More research into this important area is required. SIGNIFICANCE OF RESULTS: This systematic review summarized the literature on the use of opioid misuse risk approaches in people with cancer. The rates of reported risk range from 6 to 65%; however, true rate may be closer to 6.5-24%. Younger age, personal or familial mental health history, and history of illicit drug use consistently showed an increased risk of opioid misuse. Clinicians may choose from several approaches. Limited data are available on feasibility and patient experience. PROSPERO registration number. CRD42020163385

Optimizing 4D Cone Beam Computed Tomography Acquisition by Varying the Gantry Velocity and Projection Time Interval

Four Dimensional Cone Beam Computed Tomography (4DCBCT) is an emerging clinical image guidance strategy for tumour sites affected by respiratory motion. In current generation 4DCBCT techniques, both the gantry rotation speed and imaging frequency are constant and independent of the patient's breathing which can lead to projection clustering. We present a Mixed Integer Quadratic Programming (MIQP) model for Respiratory Motion Guided-4DCBCT (RMG-4DCBCT) which regulates the gantry velocity and projection time interval, in response to the patient's respiratory signal, so that a full set of evenly spaced projections can be taken in a number of phase, or displacement, bins during the respiratory cycle. In each respiratory bin, an image can be reconstructed from the projections to give a 4D view of the patient's anatomy so that the motion of the lungs, and tumour, can be observed during the breathing cycle. A solution to the full MIQP model in a practical amount of time, 10 seconds, is not possible with the leading commercial MIQP solvers, so a heuristic method is presented. Using parameter settings typically used on current generation 4DCBCT systems (4 minute image acquisition, 1200 projections, 10 respiratory bins) and a patient with a four second breathing period, we show that the root mean square (RMS) of the angular separation between projections with displacement binning is 2:7 degrees using existing constant gantry speed systems and 0:6degrees using RMG-4DCBCT. For phase based binning the RMS is 2:7degrees using constant gantry speed systems and 2:5 degrees using RMG-4DCBCT. The optimization algorithm presented is a critical step on the path to developing a system for RMG-4DCBCT

Reducing 4DCBCT imaging time and dose: the first implementation of variable gantry speed 4DCBCT on a linear accelerator.

Four dimensional cone beam computed tomography (4DCBCT) uses a constant gantry speed and imaging frequency that are independent of the patient's breathing rate. Using a technique called respiratory motion guided 4DCBCT (RMG-4DCBCT), we have previously demonstrated that by varying the gantry speed and imaging frequency, in response to changes in the patient's real-time respiratory signal, the imaging dose can be reduced by 50-70%. RMG-4DCBCT optimally computes a patient specific gantry trajectory to eliminate streaking artefacts and projection clustering that is inherent in 4DCBCT imaging. The gantry trajectory is continuously updated as projection data is acquired and the patient's breathing changes. The aim of this study was to realise RMG-4DCBCT for the first time on a linear accelerator. To change the gantry speed in real-time a potentiometer under microcontroller control was used to adjust the current supplied to an Elekta Synergy's gantry motor. A real-time feedback loop was developed on the microcontroller to modulate the gantry speed and projection acquisition in response to the real-time respiratory signal so that either 40, RMG-4DCBCT40, or 60, RMG-4DCBCT60, uniformly spaced projections were acquired in 10 phase bins. Images of the CIRS dynamic Thorax phantom were acquired with sinusoidal breathing periods ranging from 2 s to 8 s together with two breathing traces from lung cancer patients. Image quality was assessed using the contrast to noise ratio (CNR) and edge response width (ERW). For the average patient, with a 3.8 s breathing period, the imaging time and image dose were reduced by 37% and 70% respectively. Across all respiratory rates, RMG-4DCBCT40 had a CNR in the range of 6.5 to 7.5, and RMG-4DCBCT60 had a CNR between 8.7 and 9.7, indicating that RMG-4DCBCT allows consistent and controllable CNR. In comparison, the CNR for conventional 4DCBCT drops from 20.4 to 6.2 as the breathing rate increases from 2 s to 8 s. With RMG-4DCBCT, the ERW in the direction of motion of the imaging insert decreases from 2.1 mm to 1.1 mm as the breathing rate increases from 2 s to 8 s while for conventional 4DCBCT the ERW increases from 1.9 mm to 2.5 mm. Image quality can be controlled during 4DCBCT acquisition by varying the gantry speed and the projection acquisition in response to the patient's real-time respiratory signal. However, although the image sharpness, i.e. ERW, is improved with RMG-4DCBCT, the ERW depends on the patient's breathing rate and breathing regularity

Optimizing 4DCBCT Projection Allocation to Respiratory Bins

Four dimensional cone beam computed tomography (4DCBCT) is an emerging image guidance strategy used in radiotherapy where projections acquired during a scan are sorted into respiratory bins based on the respiratory phase or displacement. 4DCBCT reduces the motion blur caused by respiratory motion but increases streaking artefacts due to projection under-sampling as a result of the irregular nature of patient breathing and the binning algorithms used. For displacement binning the streak artefacts are so severe that displacement binning is rarely used clinically. The purpose of this study is to investigate if sharing projections between respiratory bins and adjusting the location of respiratory bins in an optimal manner can reduce or eliminate streak artefacts in 4DCBCT images. We introduce a mathematical optimization framework and a heuristic solution method, which we will call the optimized projection allocation algorithm, to determine where to position the respiratory bins and which projections to source from neighbouring respiratory bins. Five 4DCBCT datasets from three patients were used to reconstruct 4DCBCT images. Projections were sorted into respiratory bins using equispaced, equal density and optimized projection allocation. The standard deviation of the angular separation between projections was used to assess streaking and the consistency of the segmented volume of a ducial gold marker was used to assess motion blur. The standard deviation of the angular separation between projections using displacement binning and optimized projection allocation was 30%-50% smaller than conventional phase based binning and 59%-76% smaller than conventional displacement binning indicating more uniformly spaced projections and fewer streaking artefacts. The standard deviation in the marker volume was 20%-90% smaller when using optimized projection allocation than using conventional phase based binning suggesting more uniform marker segmentation and less motion blur. Images reconstructed using displacement binning and the optimized projection allocation algorithm were clearer, contained visibly fewer streak artefacts and produced more consistent marker segmentation than those reconstructed with either equispaced or equal-density binning. The optimized projection allocation algorithm signi cantly improves image quality in 4DCBCT images and provides, for the rst time, a method to consistently generate high quality displacement binned 4DCBCT images in clinical applications

Technical Note: The design and function of a horizontal patient rotation system for the purposes of fixed-beam cancer radiotherapy.

PURPOSE: Cancer radiation therapy treatment is performed by delivering a 3D dose distribution to the tumor via the relative rotation between beam and patient. While most modern machines rotate the radiation beam around a still patient, the treatment can also be delivered by rotating the patient relative to a fixed beam. Fixed-beam, patient rotation radiotherapy machines show promise for reducing the size, surface area footprint, and shielding requirements compared with rotating gantry machines. In this Technical Note, we describe the development of a bespoke horizontal patient rotation system for the purposes of a fixed-beam cancer radiotherapy architecture. METHODS: A horizontal Patient Rotation System was designed in accordance with the appropriate standards pertaining to performance and safety of medical electrical equipment and medical linear accelerators (ISO 9001, IEC 60601-1, IEC 60601-2-1, ISO 14971, ISO 13485, 21CFR820, IEC 62304, Machinery Directive 98/37/EC). The principal criteria for the design were safety, patient comfort, real-time control and the ability to be integrated with other radiation therapy componentry (including a linear accelerator and kV imaging systems). RESULTS: A first of its kind device for securing, immobilizing, translating, and rotating patients has been designed and built and tested against 161 different design, safety, and usability specifications. The device has real-time control for all critical applications. CONCLUSIONS: We designed and built a bespoke device which can translate and rotate patients 360° around a horizontal axis. The device meets all design and safety criteria with early usability tests indicating a high degree of comfort and utility. The system has been installed in a clinical bunker, integrated with a fixed-beam linear accelerator and is currently being commissioned for the purposes of cancer radiotherapy treatment

Online 4D ultrasound guidance for real-time motion compensation by MLC tracking

PURPOSE: With the trend in radiotherapy moving toward dose escalation and hypofractionation, the need for highly accurate targeting increases. While MLC tracking is already being successfully used for motion compensation of moving targets in the prostate, current real-time target localization methods rely on repeated x-ray imaging and implanted fiducial markers or electromagnetic transponders rather than direct target visualization. In contrast, ultrasound imaging can yield volumetric data in real-time (3D + time = 4D) without ionizing radiation. The authors report the first results of combining these promising techniques-online 4D ultrasound guidance and MLC tracking-in a phantom. METHODS: A software framework for real-time target localization was installed directly on a 4D ultrasound station and used to detect a 2 mm spherical lead marker inside a water tank. The lead marker was rigidly attached to a motion stage programmed to reproduce nine characteristic tumor trajectories chosen from large databases (five prostate, four lung). The 3D marker position detected by ultrasound was transferred to a computer program for MLC tracking at a rate of 21.3 Hz and used for real-time MLC aperture adaption on a conventional linear accelerator. The tracking system latency was measured using sinusoidal trajectories and compensated for by applying a kernel density prediction algorithm for the lung traces. To measure geometric accuracy, static anterior and lateral conformal fields as well as a 358° arc with a 10 cm circular aperture were delivered for each trajectory. The two-dimensional (2D) geometric tracking error was measured as the difference between marker position and MLC aperture center in continuously acquired portal images. For dosimetric evaluation, VMAT treatment plans with high and low modulation were delivered to a biplanar diode array dosimeter using the same trajectories. Dose measurements with and without MLC tracking were compared to a static reference dose using 3%/3 mm and 2%/2 mm γ-tests. RESULTS: The overall tracking system latency was 172 ms. The mean 2D root-mean-square tracking error was 1.03 mm (0.80 mm prostate, 1.31 mm lung). MLC tracking improved the dose delivery in all cases with an overall reduction in the γ-failure rate of 91.2% (3%/3 mm) and 89.9% (2%/2 mm) compared to no motion compensation. Low modulation VMAT plans had no (3%/3 mm) or minimal (2%/2 mm) residual γ-failures while tracking reduced the γ-failure rate from 17.4% to 2.8% (3%/3 mm) and from 33.9% to 6.5% (2%/2 mm) for plans with high modulation. CONCLUSIONS: Real-time 4D ultrasound tracking was successfully integrated with online MLC tracking for the first time. The developed framework showed an accuracy and latency comparable with other MLC tracking methods while holding the potential to measure and adapt to target motion, including rotation and deformation, noninvasively

Respiratory Motion Guided Four Dimensional Cone Beam Computed Tomography: Encompassing Irregular Breathing

Four dimensional cone beam computed tomography (4DCBCT) images su er from angular under sampling and bunching of projections due to a lack of feedback between the respiratory signal and the acquisition system. To address this problem, Respiratory Motion Guided 4DCBCT (RMG-4DCBCT) regulates the gantry velocity and projection time interval, in response to the patient's respiratory signal, with the aim of acquiring evenly spaced projections in a number of phase or displacement bins during the respiratory cycle. Our previous study of RMG- 4DCBCT was limited to sinusoidal breathing traces. Here we expand on that work to provide a practical algorithm for the case of real patient breathing data. We give a complete description of RMG-4DCBCT including full details on how to implement the algorithms to determine when to move the gantry and when to acquire projections in response to the patient's respiratory signal. We simulate a realistic working RMG-4DCBCT system using 112 breathing traces from 24 lung cancer patients. Acquisition used phase-based binning and parameter settings typically used on commercial 4DCBCT systems (4 minute acquisition time, 1200 projections across 10 respiratory bins), with the acceleration and velocity constraints of current generation linear accelerators. We quanti ed streaking artefacts and image noise for conventional and RMG-4DCBCT methods by reconstructing projection data selected from an oversampled set of Catphan phantom projections. RMG-4DCBCT allows us to optimally trade-o image quality, acquisition time and image dose. For example, for the same image quality and acquisition time as conventional 4DCBCT approximately half the imaging dose is needed. Alternatively, for the same imaging dose, the image quality as measured by the signal to noise ratio, is improved by 63% on average. C- arm CBCT systems, with an acceleration up to 200 degrees=s2, a velocity up to 100 degrees=s and the acquisition of 80 projections per second, allow the image acquisition time to be reduced to below 60 seconds. We have made considerable progress towards realising a system to reduce projection clustering in conventional 4DCBCT imaging and hence reduce the imaging dose to the patient

Validating and improving CT ventilation imaging by correlating with ventilation 4D-PET/CT using 68Ga-labeled nanoparticles.

PURPOSE: CT ventilation imaging is a novel functional lung imaging modality based on deformable image registration. The authors present the first validation study of CT ventilation using positron emission tomography with (68)Ga-labeled nanoparticles (PET-Galligas). The authors quantify this agreement for different CT ventilation metrics and PET reconstruction parameters. METHODS: PET-Galligas ventilation scans were acquired for 12 lung cancer patients using a four-dimensional (4D) PET/CT scanner. CT ventilation images were then produced by applying B-spline deformable image registration between the respiratory correlated phases of the 4D-CT. The authors test four ventilation metrics, two existing and two modified. The two existing metrics model mechanical ventilation (alveolar air-flow) based on Hounsfield unit (HU) change (VHU) or Jacobian determinant of deformation (VJac). The two modified metrics incorporate a voxel-wise tissue-density scaling (ρVHU and ρVJac) and were hypothesized to better model the physiological ventilation. In order to assess the impact of PET image quality, comparisons were performed using both standard and respiratory-gated PET images with the former exhibiting better signal. Different median filtering kernels (σm = 0 or 3 mm) were also applied to all images. As in previous studies, similarity metrics included the Spearman correlation coefficient r within the segmented lung volumes, and Dice coefficient d20 for the (0 - 20)th functional percentile volumes. RESULTS: The best agreement between CT and PET ventilation was obtained comparing standard PET images to the density-scaled HU metric (ρVHU) with σm = 3 mm. This leads to correlation values in the ranges 0.22 ≤ r ≤ 0.76 and 0.38 ≤ d20 ≤ 0.68, with r = 0.42 ± 0.16 and d20 = 0.52 ± 0.09 averaged over the 12 patients. Compared to Jacobian-based metrics, HU-based metrics lead to statistically significant improvements in r and d20 (p < 0.05), with density scaled metrics also showing higher r than for unscaled versions (p < 0.02). r and d20 were also sensitive to image quality, with statistically significant improvements using standard (as opposed to gated) PET images and with application of median filtering. CONCLUSIONS: The use of modified CT ventilation metrics, in conjunction with PET-Galligas and careful application of image filtering has resulted in improved correlation compared to earlier studies using nuclear medicine ventilation. However, CT ventilation and PET-Galligas do not always provide the same functional information. The authors have demonstrated that the agreement can improve for CT ventilation metrics incorporating a tissue density scaling, and also with increasing PET image quality. CT ventilation imaging has clear potential for imaging regional air volume change in the lung, and further development is warranted

DMLC tracking and gating can improve dose coverage for prostate VMAT

PURPOSE: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. METHODS: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating the observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. RESULTS: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD99% and PTV D95% values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D99% for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V65% for the individual fractions from planned ranged from -44% to 101% and for the bladder V65% the range was -61% to 26% from planned. The application of tracking decreased the maximum rectum and bladder V65% difference to 6% and 4%, respectively. CONCLUSIONS: For the first time, the dosimetric impact of DMLC tracking and gating to account for intrafraction motion during prostate radiotherapy has been assessed and compared with no motion correction. Without motion correction intrafraction prostate motion can result in a significant decrease in target dose coverage for a small number of individual fractions. This is unlikely to effect the overall treatment for most patients undergoing conventionally fractionated treatments. Both DMLC tracking and gating demonstrate dose distributions for all assessed fractions that are robust to intrafraction motion

Motion management within two respiratory-gating windows: feasibility study of dual quasi-breath-hold technique in gated medical procedures.

A dual quasi-breath-hold (DQBH) technique is proposed for respiratory motion management (a hybrid technique combining breathing-guidance with breath-hold task in the middle). The aim of this study is to test a hypothesis that the DQBH biofeedback system improves both the capability of motion management and delivery efficiency. Fifteen healthy human subjects were recruited for two respiratory motion measurements (free breathing and DQBH biofeedback breathing for 15 min). In this study, the DQBH biofeedback system utilized the abdominal position obtained using an real-time position management (RPM) system (Varian Medical Systems, Palo Alto, USA) to audio-visually guide a human subject for 4 s breath-hold at EOI and 90% EOE (EOE90%) to improve delivery efficiency. We investigated the residual respiratory motion and the delivery efficiency (duty-cycle) of abdominal displacement within the gating window. The improvement of the abdominal motion reproducibility was evaluated in terms of cycle-to-cycle displacement variability, respiratory period and baseline drift. The DQBH biofeedback system improved the abdominal motion management capability compared to that with free breathing. With a phase based gating (mean ± std: 55  ±  5%), the averaged root mean square error (RMSE) of the abdominal displacement in the dual-gating windows decreased from 2.26 mm of free breathing to 1.16 mm of DQBH biofeedback (p-value = 0.007). The averaged RMSE of abdominal displacement over the entire respiratory cycles reduced from 2.23 mm of free breathing to 1.39 mm of DQBH biofeedback breathing in the dual-gating windows (p-value = 0.028). The averaged baseline drift dropped from 0.9 mm min(-1) with free breathing to 0.09 mm min(-1) with DQBH biofeedback (p-value = 0.048). The averaged duty-cycle with an 1 mm width of displacement bound increased from 15% of free breathing to 26% of DQBH biofeedback (p-value = 0.003). The study demonstrated that the DQBH biofeedback system has the potential to significantly reduce the residual respiratory motion with the improved duty cycle during the respiratory gating procedure