Real-time delivered dose assessment in carbon ion therapy of moving targets.

Objective. Real-time adaptive particle therapy is being investigated as a means to maximize the treatment delivery accuracy. To react to dosimetric errors, a system for fast and reliable verification of the agreement between planned and delivered doses is essential. This study presents a clinically feasible, real-time 4D-dose reconstruction system, synchronized with the treatment delivery and motion of the patient, which can provide the necessary feedback on the quality of the delivery.Approach. A GPU-based analytical dose engine capable of millisecond dose calculation for carbon ion therapy has been developed and interfaced with the next generation of the dose delivery system (DDS) in use at Centro Nazionale di Adroterapia Oncologica (CNAO). The system receives the spot parameters and the motion information of the patient during the treatment and performs the reconstruction of the planned and delivered 4D-doses. After each iso-energy layer, the results are displayed on a graphical user interface by the end of the spill pause of the synchrotron, permitting verification against the reference dose. The framework has been verified experimentally at CNAO for a lung cancer case based on a virtual phantom 4DCT. The patient's motion was mimicked by a moving Ionization Chamber (IC) 2D-array.Mainresults. For the investigated static and 4D-optimized treatment delivery cases, real-time dose reconstruction was achieved with an average pencil beam dose calculation speed up to more than one order of magnitude smaller than the spot delivery. The reconstructed doses have been benchmarked against offline log-file based dose reconstruction with the TRiP98 treatment planning system, as well as QA measurements with the IC 2D-array, where an average gamma-index passing rate (3%/3 mm) of 99.8% and 98.3%, respectively, were achieved.Significance. This work provides the first real-time 4D-dose reconstruction engine for carbon ion therapy. The framework integration with the CNAO DDS paves the way for a swift transition to the clinics.

Is clinical target volume necessary for locally advanced non-small cell lung cancer treated with 4D-CT intensity-modulated radiation therapy.

BACKGROUND: A dosimetric evaluation is still lacking in terms of clinical target volume (CTV) omission in stage III patients treated with 4D-CT Intensity-Modulated Radiation Therapy (IMRT). METHODS: 49 stage III NSCLC patients received 4D-CT IMRT were reviewed. Target volumes and organs at risk (OARs) were re-delineated. Four IMRT plans were conducted retrospectively to deliver different prescribed dose (74 Gy-60 Gy), and with or without CTV implementation. Dose and volume histogram (DVH) parameters were collected and compared. RESULTS: In the PTV-g 60 Gy plan (PTV-g refers to the PTV generated from the internal gross tumor volume), only 5 of 49 patients had the isodose ≥ 50 Gy line covering at least 95% of the PTV-c (PTV-c refers to the PTV generated from the internal CTV) volume. When the prescribed dose was elevated to 74 Gy to the PTV-g, 33 of 49 patients could have the isodose ≥ 50 Gy line covering at least 95% of the PTV-c volume. In terms of OARs protection, the SIB-IMRT plan showed the lowest value of V5, V20, and mean dose of lung, had the lowest V55 of esophagus, and the lowest estimated radiation doses to immune cells (EDIC). The V20, V30, and mean dose of heart was lower in the simultaneous integrated boost (SIB) IMRT (SIB-IMRT) plan than that of the PTV-c 60 Gy plan. CONCLUSIONS: CTV omission was not suitable for stage III patients when the prescribed dose to PTV-g was 60 Gy in the era of 4D-CT IMRT. CTV omission plus high dose to PTV-g (74 Gy for example) warranted further exploration. The SIB-IMRT plan had the best protection to normal tissue including lymphocytes, and might be the optimal choice.

Impact of interplay effects on spot scanning proton therapy with motion mitigation techniques for lung cancer: SFUD versus robustly optimized IMPT plans utilizing a four-dimensional dynamic dose simulation tool.

BACKGROUND: The interaction between breathing motion and scanning beams causes interplay effects in spot-scanning proton therapy for lung cancer, resulting in compromised treatment quality. This study investigated the effects and clinical robustness of two types of spot-scanning proton therapy with motion-mitigation techniques for locally advanced non-small cell lung cancer (NSCLC) using a new simulation tool (4DCT-based dose reconstruction). METHODS: Three-field single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans combined with gating and re-scanning techniques were created using a VQA treatment planning system for 15 patients with locally advanced NSCLC (70 GyRBE/35 fractions). In addition, gating windows of three or five phases around the end-of-expiration phase and two internal gross tumor volumes (iGTVs) were created, and a re-scanning number of four was used. First, the static dose (SD) was calculated using the end-of-expiration computed tomography (CT) images. The four-dimensional dynamic dose (4DDD) was then calculated using the SD plans, 4D-CT images, and the deformable image registration technique on end-of-expiration CT. The target coverage (V98%, V100%), homogeneity index (HI), and conformation number (CN) for the iGTVs and organ-at-risk (OAR) doses were calculated for the SD and 4DDD groups and statistically compared between the SD, 4DDD, SFUD, and IMPT treatment plans using paired t-test. RESULTS: In the 3- and 5-phase SFUD, statistically significant differences between the SD and 4DDD groups were observed for V100%, HI, and CN. In addition, statistically significant differences were observed for V98%, V100%, and HI in phases 3 and 5 of IMPT. The mean V98% and V100% in both 3-phase plans were within clinical limits (> 95%) when interplay effects were considered; however, V100% decreased to 89.3% and 94.0% for the 5-phase SFUD and IMPT, respectively. Regarding the significant differences in the deterioration rates of the dose volume histogram (DVH) indices, the 3-phase SFUD plans had lower V98% and CN values and higher V100% values than the IMPT plans. In the 5-phase plans, SFUD had higher deterioration rates for V100% and HI than IMPT. CONCLUSIONS: Interplay effects minimally impacted target coverage and OAR doses in SFUD and robustly optimized IMPT with 3-phase gating and re-scanning for locally advanced NSCLC. However, target coverage significantly declined with an increased gating window. Robustly optimized IMPT showed superior resilience to interplay effects, ensuring better target coverage, prescription dose adherence, and homogeneity than SFUD. TRIAL REGISTRATION: None.

Data-driven rapid 4D cone-beam CT reconstruction for new generation linacs.

Objective.Newer generation linear accelerators (Linacs) allow 20 s cone-beam CT (CBCT) acquisition which reduces radiation therapy treatment time. However, the current clinical application of these rapid scans is only 3DCBCT. In this paper we propose a novel data-driven rapid 4DCBCT reconstruction method for new generation linacs.Approach.This method relies on estimating the magnitude of the diaphragm motion from an initial 3D reconstruction. This estimated motion is used to linearly approximate a deformation vector field (DVF) for each respiration phase. These DVFs are then used for motion compensated Feldkamp-Davis-Kress (MCFDK) reconstructions. This method, named MCFDK Data Driven (MCFDK-DD), was compared to a MCFDK reconstruction using a prior motion model (MCFDK-Prior), a 3D-FDK reconstruction, and a conventional acquisition (4 mins) conventional reconstruction 4DCBCT (4D-FDK). The data used in this paper were derived from 4DCT volumes from 12 patients from The Cancer Imaging Archives. Image quality was quantified using RMSE of line plots centred on the tumour, tissue interface width (TIW), the mean square error (MSE) and structural similarity index measurement (SSIM).Main Results.The tumour line plots in the Superior-Inferior direction showed reduced RMSE for the MCFDK-DD compared to the 3D-FDK method, indicating the MCFDK-DD method provided a more accurate tumour location. Similarly, the TIW values from the MCFDK-DD reconstructions (median 8.6 mm) were significantly reduced for the MCFDK-DD method compared to the 3D-FDK reconstructions (median 14.8 mm, (p< 0.001). The MCFDK-DD, MCFDK-Prior and 3D-FDK had median MSE values of1.08×10-6mm-1,1.11×10-6mm-1and1.17×10-6mm-1respectively. The corresponding median SSIM values were 0.93, 0.92 and 0.92 respectively indicating the MCFDK-DD had good agreement with the conventional 4D-FDK reconstructions.Significance.These results demonstrate the feasibility of creating accurate data-driven 4DCBCT images for rapid scans on new generation linacs. These findings could lead to increased clinical usage of 4D information on newer generation linacs.

Impact of perioperative diagnostic tools on clinical outcomes and cost-effectiveness in parathyroid surgery: a decision model-based analysis.

OBJECTIVES: Preoperative and intraoperative diagnostic tools influence the surgical management of primary hyperparathyroidism (PHPT), whereby their performance of classification varies considerably for the two common causes of PHPT: solitary adenomas and multiglandular disease. A consensus on the use of such diagnostic tools for optimal perioperative management of all PHPT patients has not been reached. DESIGN: A decision tree model was constructed to estimate and compare the clinical outcomes and the cost-effectiveness of preoperative imaging modalities and intraoperative parathyroid hormone (ioPTH) monitoring criteria in a 21-year time horizon with a 3% discount rate. The robustness of the model was assessed by conducting a one-way sensitivity analysis and probabilistic uncertainty analysis. SETTING: The US healthcare system. POPULATION: A hypothetical population consisting of 5000 patients with sporadic, symptomatic or asymptomatic PHPT. INTERVENTIONS: Preoperative and intraoperative diagnostic modalities for parathyroidectomy. MAIN OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), net monetary benefits (NMBs) and clinical outcomes. RESULTS: In the base-case analysis, four-dimensional (4D) CT was the least expensive strategy with US$10 276 and 15.333 QALYs. Ultrasound and 99mTc-Sestamibi single-photon-emission CT/CT were both dominated strategies while 18F-fluorocholine positron emission tomography was cost-effective with an NMB of US$416 considering a willingness to pay a threshold of US$95 958. The application of ioPTH monitoring with the Vienna criterion decreased the rate of reoperations from 10.50 to 0.58 per 1000 patients compared to not using ioPTH monitoring. Due to an increased rate of bilateral neck explorations from 257.45 to 347.45 per 1000 patients, it was not cost-effective. CONCLUSIONS: 4D-CT is the most cost-effective modality for the preoperative localisation of solitary parathyroid adenomas and multiglandular disease. The use of ioPTH monitoring is not cost-effective, but to minimise clinical complications, the Miami criterion should be applied for suspected solitary adenomas and the Vienna criterion for multiglandular disease.

Analyzing RPM and RGSC Infrared Camera Sensitivity: A Comparative Study of Breathing Cycle Replication Verifications and Limitations.

OBJECTIVE: This study addresses challenges in delivering high radiation doses and managing organ motion in Stereotactic Body Radiation Therapy (SBRT) for thoracic and abdominal cancer. It evaluates Varian's Real Time Position Management (RPM) system's infrared camera sensitivity during crucial Four-Dimensional computed tomography (4D-CT) scans for planning and treatment. The analysis includes CT simulator, LINAC (Novalis Tx and TrueBeam STx). This research enhances SBRT precision by offering insights into RPM and RGSC system performance across machines, impacting treatment planning and delivery optimization. METHODS: The QUASAR™ Respiratory Motion Assembly phantom is aligned with precision using lasers. It is configured with either six-dot reflective or four-dot lens marker blocks featuring a retroreflective marker placed on the phantom's surface. Motion is induced by adjusting the amplitude, and the camera position is finely tuned to monitor the marker's movements. This investigation entails variations in seconds per breath (SPB) within the Quasar breath platform, specifically at intervals of 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 seconds while maintaining a 1cm amplitude camera setting. RESULT: For TrueBeam-STx: Ensure SPB values are kept above 1.8 seconds for accurate replication. For Novalis-Tx: Stay within an SPB range of up to 2.0 seconds for reliable reproducibility. For CT Simulator: Optimal replication up to an SPB of 2.2 seconds; avoid SPB values below 1.8 seconds for reliable detection. CONCLUSION: Data for TrueBeam-STx, Novalis-Tx, and the CT simulator shows discrepancies in replicating the breathing cycle as Seconds Per Breath (SPB) decreases. Effective Infrared (IR) sensitivity is observed until SPB thresholds: 1.8s (TrueBeam-STx), 2.2s (Novalis-Tx), and 2.2s (CT simulator). We should consider values equal to or greater than the mentioned breathing periods. Variations in replicating breathing cycles signal challenges in planning and delivering treatments, especially with lower SPB values. These insights guide clinicians to adapt treatments based on machine-specific capabilities for accurate and reproducible outcomes.

Adaptive intensity modulated proton therapy using 4D robust planning: a proof-of-concept for the application of dose mimicking approach.

Objective.A four-dimensional robust optimisation (4DRO) is usually employed when the tumour respiratory motion needs to be addressed. However, it is computationally demanding, and an automated method is preferable for adaptive planning to avoid manual trial-and-error. This study proposes a 4DRO technique based on dose mimicking for automated adaptive planning.Approach.Initial plans for 4DRO intensity modulated proton therapy were created on an average CT for four patients with clinical target volume (CTV) in the lung, oesophagus, or pancreas, respectively. These plans were robustly optimised using three phases of four-dimensional computed tomography (4DCT) and accounting for setup and density uncertainties. Weekly 4DCTs were used for adaptive replanning, using a constant relative biological effectiveness (cRBE) of 1.1. Two methods were used: (1) template-based adaptive (TA) planning and (2) dose-mimicking-based adaptive (MA) planning. The plans were evaluated using variable RBE (vRBE) weighted doses and biologically consistent dose accumulation (BCDA).Main results.MA and TA plans had comparable CTV coverage except for one patient where the MA plan had a higher D98 and lower D2 but with an increased D2 in few organs at risk (OARs). CTV D98 deviations in non-adaptive plans from the initial plans were up to -7.2 percentage points (p.p.) in individual cases and -1.8 p.p. when using BCDA. For the OARs, MA plans showed a reduced mean dose and D2 compared to the TA plans, with few exceptions. The vRBE-weighted accumulated doses had a mean dose and D2 difference of up to 0.3 Gy and 0.5 Gy, respectively, in the OARs with respect to cRBE-weighted doses.Significance.MA plans indicate better performance in target coverage and OAR dose sparing compared to the TA plans in 4DRO adaptive planning. Moreover, MA method is capable of handling both forms of anatomical variation, namely, changes in density and relative shifts in the position of OARs.

Quantifying irregular pulsation of intracranial aneurysms using 4D-CTA.

Recent studies have suggested that irregular pulsation of intracranial aneurysm during the cardiac cycle may be potentially associated with aneurysm rupture risk. However, there is a lack of quantification method for irregular pulsations. This study aims to quantify irregular pulsations by the displacement and strain distribution of the intracranial aneurysm surface during the cardiac cycle using four-dimensional CT angiographic image data. Four-dimensional CT angiography was performed in 8 patients. The image data of a cardiac cycle was divided into approximately 20 phases, and irregular pulsations were detected in four intracranial aneurysms by visual observation, and then the displacement and strain of the intracranial aneurysm was quantified using coherent point drift and finite element method. The displacement and strain were compared between aneurysms with irregular and normal pulsations in two different ways (total and stepwise). The stepwise first principal strain was significantly higher in aneurysms with irregular than normal pulsations (0.20±0.01 vs 0.16±0.02, p=0.033). It was found that the irregular pulsations in intracranial aneurysms usually occur during the consecutive ascending or descending phase of volume changes during the cardiac cycle. In addition, no statistically significant difference was found in the aneurysm volume changes over the cardiac cycle between the two groups. Our method can successfully quantify the displacement and strain changes in the intracranial aneurysm during the cardiac cycle, which may be proven to be a useful tool to quantify intracranial aneurysm deformability and aid in aneurysm rupture risk assessment.

[Dynamics Evaluation of Remodeling Operation Using 4-dimentional Computed Tomography].

OBJECTIVES: The extensibility of the aortic root after the remodeling procedure was evaluated using 4-dimentional computed tomography( 4D-CT). PATIENTS AND METHODS: Seventeen patients( 13 males/4 females), mean age 52 years, who had undergone the remodeling procedure in the last 3 years were included. To understand the dynamics of the aortic root after reconstruction, the R-R interval on the electrocardiogram was divided into 10 equal parts, and the percentage change in area of the basal ring/Valsalva sinus/sino-tubular junction (STJ) level was calculated to evaluate the extensibility of the aortic root. For the basal ring, changes in ellipticity and circumference were also compared. RESULTS: Basal ring, Valsalva sinus, and STJ area changes with cardiac cycle were similar to those in the control group. Basal ring showed a regular circle in systole and an oval in diastole, and its circumference was enlarged in systole. CONCLUSIONS: The use of 4D-CT made it possible to evaluate the extensibility of the aortic root after remodeling procedure. In particular, the mobility of the basal ring is large, suggesting that it guarantees the physiological opening and closing of the valve and contributes to its durability.

Quantitative assessment of intertarget position variations based on 4D-CT and 4D-CBCT simulations in single-isocenter multitarget lung stereotactic body radiation therapy.

BACKGROUND: In single-isocenter multitarget stereotactic body radiotherapy (SBRT), geometric miss risks arise from uncertainties in intertarget position. However, its assessment is inadequate, and may be interfered by the reconstructed tumor position errors (RPEs) during simulated CT and cone beam CT (CBCT) acquisition. This study aimed to quantify intertarget position variations and assess factors influencing it. METHODS: We analyzed data from 14 patients with 100 tumor pairs treated with single-isocenter SBRT. Intertarget position variation was measured using 4D-CT simulation to assess the intertarget position variations (ΔD) during routine treatment process. Additionally, a homologous 4D-CBCT simulation provided RPE-free comparison to determine the impact of RPEs, and isolating purely tumor motion induced ΔD to evaluate potential contributing factors. RESULTS: The median ΔD was 4.3 mm (4D-CT) and 3.4 mm (4D-CBCT). Variations exceeding 5 mm and 10 mm were observed in 31.1% and 5.5% (4D-CT) and 20.4% and 3.4% (4D-CBCT) of fractions, respectively. RPEs necessitated an additional 1-2 mm safety margin. Intertarget distance and breathing amplitude variability showed weak correlations with variation (Rs = 0.33 and 0.31). The ΔD differed significantly by locations (upper vs. lower lobe and right vs. Left lung). Notably, left lung tumor pairs exhibited the highest risk. CONCLUSIONS: This study provide a reliable way to assess intertarget position variation by using both 4D-CT and 4D-CBCT simulation. Consequently, single-isocenter SBRT for multiple lung tumors carries high risk of geometric miss. Tumor motion and RPE constitute a substantial portion of intertarget position variation, requiring correspondent strategies to minimize the intertarget uncertainties.

Dynamic reconstruction for digital tomosynthesis: a phantom proof of concept for breast care.

Objective. Digital tomosynthesis (DTS) is a type of limited-angle Computed Tomography (CT) used in orthopedic and oncology care to provide a pseudo-3D reconstructed volume of a body part from multiple x-ray projections. Patient motion during acquisitions results in artifacts which affect screening and diagnostic performances. Hence, accurate reconstruction of moving body parts from a tomosynthesis projection series is addressed in this paper, with a particular focus on the breast. The aim of this paper is to assess the feasibility of a novel dynamic reconstruction technique for DTS and evaluate its accuracy compared to an available ground truth.Approach. The proposed method is a combination of a 4D dynamic tomography strategy leveraging the formalism of Projection-based Digital Volume Correlation (P-DVC) with a multiscale approach to estimate and correct patient motion. Iterations of two operations are performed: (i) a motion-corrected reconstruction based on the Simultaneous Iterative Reconstruction Technique (SIRT) algorithm and (ii) a motion estimation from projection residuals, to obtain motion-free volumes. Performance is evaluated on a synthetic Digital Breast Tomosynthesis (DBT) case. Three slabs of a CIRS breast phantom are imaged on a Senographe PristinaTM, under plate-wise rigid body motions with amplitudes ranging up to 10 mm so that an independent measurement of the motion can be accessed.Results. Results show a motion estimation average precision down to 0.183 mm (1.83 voxels), when compared to the independent measurement. Moreover, an 84.2% improvement on the mean residual error and a 59.9% improvement on the root mean square error (RMSE) with the original static reconstruction are obtained.Significance. Visual and quantitative assessments of the dynamically reconstructed volumes show that the proposed method fully restores conspicuity for important clinical features contained in the phantom.

Verification of acromion marker cluster and scapula spinal marker cluster methods for tracking shoulder kinematics: a comparative study with upright four-dimensional computed tomography.

BACKGROUND: This study validated the accuracy of the acromion marker cluster (AMC) and scapula spinal marker cluster (SSMC) methods compared with upright four-dimensional computed tomography (4DCT) analysis. METHODS: Sixteen shoulders of eight healthy males underwent AMC and SSMC assessments. Active shoulder elevation was tracked using upright 4DCT and optical motion capture system. The scapulothoracic and glenohumeral rotation angles calculated from AMC and SSMC were compared with 4DCT. Additionally, the motion of these marker clusters on the skin with shoulder elevation was evaluated. RESULTS: The average differences between AMC and 4DCT during 10°-140° of humerothoracic elevation were - 2.2° ± 7.5° in scapulothoracic upward rotation, 14.0° ± 7.4° in internal rotation, 6.5° ± 7.5° in posterior tilting, 3.7° ± 8.1° in glenohumeral elevation, - 8.3° ± 10.7° in external rotation, and - 8.6° ± 8.9° in anterior plane of elevation. The difference between AMC and 4DCT was significant at 120° of humerothoracic elevation in scapulothoracic upward rotation, 50° in internal rotation, 90° in posterior tilting, 120° in glenohumeral elevation, 100° in external rotation, and 100° in anterior plane of elevation. However, the average differences between SSMC and 4DCT were - 7.5 ± 7.7° in scapulothoracic upward rotation, 2.0° ± 7.0° in internal rotation, 2.3° ± 7.2° in posterior tilting, 8.8° ± 7.9° in glenohumeral elevation, 2.0° ± 9.1° in external rotation, and 1.9° ± 10.1° in anterior plane of elevation. The difference between SSMC and 4DCT was significant at 50° of humerothoracic elevation in scapulothoracic upward rotation and 60° in glenohumeral elevation, with no significant differences observed in other rotations. Skin motion was significantly smaller in AMC (28.7 ± 4.0 mm) than SSMC (38.6 ± 5.8 mm). Although there was smaller skin motion in AMC, SSMC exhibited smaller differences in scapulothoracic internal rotation, posterior tilting, glenohumeral external rotation, and anterior plane of elevation compared to 4DCT. CONCLUSION: This study demonstrates that AMC is more accurate for assessing scapulothoracic upward rotation and glenohumeral elevation, while SSMC is preferable for evaluating scapulothoracic internal rotation, posterior tilting, glenohumeral external rotation, and anterior plane of elevation, with smaller differences compared to 4DCT.

A prospective observational study evaluating two patient immobilisation methods in lung stereotactic radiotherapy.

PURPOSE: The main objective of this study was to assess inter- and intrafraction errors for two patient immobilisation devices in the context of lung stereotactic body radiation therapy: a vacuum cushion and a simple arm support. MATERIALS AND METHODS: Twenty patients who were treated with lung stereotactic body radiation therapy in supine position with arms above their head were included in the study. Ten patients were setup in a vacuum cushion (Bluebag™, Elekta) and ten other patients with a simple arm support (Posirest™, Civco). A pretreatment four-dimensional cone-beam computed tomography and a post-treatment three-dimensional cone-beam computed tomography were acquired to compare positioning and immobilisation accuracy. Based on a rigid registration with the planning computed tomography on the spine at the target level, translational and rotational errors were reported. RESULTS: The median number of fractions per treatment was 5 (range: 3-10). Mean interfraction errors based on 112 four-dimensional cone-beam computed tomographies were similar for both setups with deviations less than or equal to 1.3mm in lateral and vertical direction and 1.2° in roll and yaw. For longitudinal translational errors, mean interfraction errors were 0.7mm with vacuum cushion and -3.9mm with arm support. Based on 111 three-dimensional cone-beam computed tomographies, mean lateral, longitudinal and vertical intrafraction errors were -0.1mm, -0.2mm and 0.0mm respectively (SD: 1.0, 1.2 and 1.0mm respectively) for the patients setup with vacuum cushion, and mean vertical, longitudinal and lateral intrafraction errors were -0.3mm, -0.7mm and 0.1mm respectively (SD: 2.3, 1.8 and 1.4mm respectively) for the patients setup with arm support. Intrafraction errors means were not statistically different between both positions but standard deviations were statistically larger with arm support. CONCLUSION: The results of our study showed similar inter and intrafraction mean deviations between both positioning but a large variability in intrafraction observed with arm support suggested a more accurate immobilization with vacuum cushion.

Robustness of intensity modulated proton treatment of esophageal cancer for anatomical changes and breathing motion.

BACKGROUND AND PURPOSE: In this study, we assessed the robustness of intensity modulated proton therapy (IMPT) in esophageal cancer for anatomical variations during treatment. METHODS: The first sixty esophageal cancer patients, treated clinically with chemoradiotherapy were included. The treatment planning strategy was based on an internal target volume (ITV) approach, where the ITV was created from the clinical target volumes (CTVs) delineated on all phases of a 4DCT. For optimization, a 3 mm isotropic margin was added to the ITV, combined with robust optimization using 5 mm setup and 3 % range uncertainty. Each patient received weekly repeat CTs (reCTs). Robust plan re-evaluation on all reCTs, and a robust dose summation was performed. To assess the factors influencing ITV coverage, a multivariate linear regression analysis was performed. Additionally, clinical adaptations were evaluated. RESULTS: The target coverage was adequate (ITV V94%>98 % on the robust voxel-wise minimum dose) on most reCTs (91 %), and on the summed dose in 92 % of patients. Significant predictors for ITV coverage in the multivariate analysis were diaphragm baseline shift and water equivalent depth (WED) of the ITV in the beam direction. Underdosage of the ITV mainly occurred in week 1 and 4, leading to treatment adaptation of eight patients, all on the first reCT. CONCLUSION: Our IMPT treatment of esophageal cancer is robust for anatomical variations. Adaptation appears to be most effective in the first week of treatment. Diaphragm baseline shifts and WED are predictive factors for ITV underdosage, and should be incorporated in an adaptation protocol.

Improving the Feasibility of Mitigating Phase Errors in 4DCT caused by a Random Reference Breathing Pattern in the Quasar Phantom and the Role of Slice Thickness.

PURPOSE: The study aimed to validate a method for minimizing phase errors by combining full-length lung 4DCT (f4DCT) scans with shorter tumor-restricted 4DCT (s4DCT) scans. It assessed the feasibility of integrating two scans one covering the entire phantom length and the other focused on the tumor area. The study also evaluated the impact of Maximum Intensity Projection (MIP) volume and imaging dose for different slice thicknesses (2.5mm and 1.25mm) in both full-length and short target-restricted 4DCT scans. METHODS: The study utilized the Quasar Programmable Respiratory Motion Phantom, simulating tumor motion with a variable lung insert. The setup included a tumor replica and a six-dot IR reflector marker on the breathing platform. The objective was to analyze volume differences in fMIP_2.5mm compared to sMIP_1.25mm within their respective 4D_MIP CT series. This involved varying breathing periods (2.5s, 3.0s, 4.0s, and 5.0s) and longitudinal tumor sizes (6mm, 8mm, and 10mm). The study also assessed exposure time and expected CTDIvol of s4D_2.5mm and s4D_1.25mm for different breathing periods (5.0s to 2.0s) in the sinusoidal wave motion of the six-dot marker on the breathing platform. RESULTS: Conducting two consecutive 4DCT scans is viable for patients with challenging breathing patterns or when the initial lung tumor scan is in close proximity to the tumor location, eliminating the need for an additional full-length 4DCT. The analysis involves assessing MIP volume, imaging dose (CTDIvol), and exposure time. Longitudinal tumor shifts for 6mm are [16.6-17.2] in fMIP_2.5mm and [16.8-17.5] in sMIP_1.25mm, for 8mm [17.2-18.3] in fMIP_2.5mm and [17.8-18.4] in sMIP_1.25mm, and for 10mm [19-19.9] in fMIP_2.5mm and [19.4-20] in sMIP_1.25mm (p≥ 0.005), respectively. CONCLUSION: The Quasar Programmable Respiratory Motion Phantom accurately replicated varied breathing patterns and tumor motions. Comprehensive analysis was facilitated through detailed manual segmentation of Internal Target Volumes and Internal Gross Target Volumes.

Robust optimization of the Gross Tumor Volume compared to conventional Planning Target Volume-based planning in photon Stereotactic Body Radiation Therapy of lung tumors.

BACKGROUND: Robust optimization has been suggested as an approach to reduce the irradiated volume in lung Stereotactic Body Radiation Therapy (SBRT). We performed a retrospective planning study to investigate the potential benefits over Planning Target Volume (PTV)-based planning. MATERIAL AND METHODS: Thirty-nine patients had additional plans using robust optimization with 5-mm isocenter shifts of the Gross Tumor Volume (GTV) created in addition to the PTV-based plan used for treatment. The optimization included the mid-position phase and the extreme breathing phases of the 4D-CT planning scan. The plans were compared for tumor coverage, isodose volumes, and doses to Organs At Risk (OAR). Additionally, we evaluated both plans with respect to observed tumor motion using the peak tumor motion seen on the planning scan and cone-beam CTs. RESULTS: Statistically significant reductions in irradiated isodose volumes and doses to OAR were achieved with robust optimization, while preserving tumor dose. The reductions were largest for the low-dose volumes and reductions up to 188 ccm was observed. The robust evaluation based on observed peak tumor motion showed comparable target doses between the two planning methods. Accumulated mean GTV-dose was increased by a median of 4.46 Gy and a non-significant increase of 100 Monitor Units (MU) was seen in the robust optimized plans. INTERPRETATION: The robust plans required more time to prepare, and while it might not be a feasible planning strategy for all lung SBRT patients, we suggest it might be useful for selected patients.

A review on 4D cone-beam CT (4D-CBCT) in radiation therapy: Technical advances and clinical applications.

Cone-beam CT (CBCT) is the most commonly used onboard imaging technique for target localization in radiation therapy. Conventional 3D CBCT acquires x-ray cone-beam projections at multiple angles around the patient to reconstruct 3D images of the patient in the treatment room. However, despite its wide usage, 3D CBCT is limited in imaging disease sites affected by respiratory motions or other dynamic changes within the body, as it lacks time-resolved information. To overcome this limitation, 4D-CBCT was developed to incorporate a time dimension in the imaging to account for the patient's motion during the acquisitions. For example, respiration-correlated 4D-CBCT divides the breathing cycles into different phase bins and reconstructs 3D images for each phase bin, ultimately generating a complete set of 4D images. 4D-CBCT is valuable for localizing tumors in the thoracic and abdominal regions where the localization accuracy is affected by respiratory motions. This is especially important for hypofractionated stereotactic body radiation therapy (SBRT), which delivers much higher fractional doses in fewer fractions than conventional fractionated treatments. Nonetheless, 4D-CBCT does face certain limitations, including long scanning times, high imaging doses, and compromised image quality due to the necessity of acquiring sufficient x-ray projections for each respiratory phase. In order to address these challenges, numerous methods have been developed to achieve fast, low-dose, and high-quality 4D-CBCT. This paper aims to review the technical developments surrounding 4D-CBCT comprehensively. It will explore conventional algorithms and recent deep learning-based approaches, delving into their capabilities and limitations. Additionally, the paper will discuss the potential clinical applications of 4D-CBCT and outline a future roadmap, highlighting areas for further research and development. Through this exploration, the readers will better understand 4D-CBCT's capabilities and potential to enhance radiation therapy.

Lung sparing in MR-guided non-adaptive SBRT treatment of peripheral lung tumors.

Objective.We aim to: (1) quantify the benefits of lung sparing using non-adaptive magnetic resonance guided stereotactic body radiotherapy (MRgSBRT) with advanced motion management for peripheral lung cancers compared to conventional x-ray guided SBRT (ConvSBRT); (2) establish a practical decision-making guidance metric to assist a clinician in selecting the appropriate treatment modality.Approach.Eleven patients with peripheral lung cancer who underwent breath-hold, gated MRgSBRT on an MR-guided linear accelerator (MR linac) were studied. Four-dimensional computed tomography (4DCT)-based retrospective planning using an internal target volume (ITV) was performed to simulate ConvSBRT, which were evaluated against the original MRgSBRT plans. Metrics analyzed included planning target volume (PTV) coverage, various lung metrics and the generalized equivalent unform dose (gEUD). A dosimetric predictor for achievable lung metrics was derived to assist future patient triage across modalities.Main results.PTV coverage was high (median V100% > 98%) and comparable for both modalities. MRgSBRT had significantly lower lung doses as measured by V20 (median 3.2% versus 4.2%), mean lung dose (median 3.3 Gy versus 3.8 Gy) and gEUD. Breath-hold, gated MRgSBRT resulted in an average reduction of 47% in PTV volume and an average increase of 19% in lung volume. Strong correlation existed between lung metrics and the ratio of PTV to lung volumes (RPTV/Lungs) for both modalities, indicating that RPTV/Lungsmay serve as a good predictor for achievable lung metrics without the need for pre-planning. A threshold value of RPTV/Lungs< 0.035 is suggested to achieve V20 < 10% using ConvSBRT. MRgSBRT should otherwise be considered if the threshold cannot be met.Significance.The benefits of lung sparing using MRgSBRT were quantified for peripheral lung tumors; RPTV/Lungswas found to be an effective predictor for achievable lung metrics across modalities. RPTV/Lungscan assist a clinician in selecting the appropriate modality without the need for labor-intensive pre-planning, which has significant practical benefit for a busy clinic.

Impact of setup and geometric uncertainties on the robustness of free-breathing photon radiotherapy of small lung tumors.

PURPOSE: Respiratory motion and patient setup error both contribute to the dosimetric uncertainty in radiotherapy of lung tumors. Managing these uncertainties for free-breathing treatments is usually done by margin-based approaches or robust optimization. However, breathing motion can be irregular and concerns have been raised for the robustness of the treatment plans. We have previously reported the dosimetric effects of the respiratory motion, without setup uncertainties, in lung tumor photon radiotherapy using free-breathing images. In this study, we include setup uncertainty. METHODS: Tumor positions from cine-CT images acquired in free-breathing were combined with per-fraction patient shifts to simulate treatment scenarios. A total of 14 patients with 300 tumor positions were used to evaluate treatment plans based on 4DCT. Four planning methods aiming at delivering 54 Gy as median tumor dose in three fractions were compared. The planning methods were denoted robust 4D (RB4), isodose to the PTV with a central higher dose (ISD), the ISD method normalized to the intended median tumor dose (IRN) and homogeneous fluence to the PTV (FLU). RESULTS: For all planning methods 95% of the intended dose was achieved with at least 90% probability with RB4 and FLU having equal CTV D50% values at this probability. FLU gave the most consistent results in terms of CTV D50% spread and dose homogeneity. CONCLUSIONS: Despite the simulated patient shifts and tumor motions being larger than observed in the 4DCTs the dosimetric impact was suggested to be small. RB4 or FLU are recommended for the planning of free-breathing treatments.

Post-processing of quantitative 4D-CT for initial evaluation of scapholunate Instability: Assessment of simplified approaches to data analysis.

OBJECTIVES: To evaluate the diagnostic performance of simplified post-processing approaches for quantitative wrist 4D-CT in the assessment of scapholunate instability (SLI). METHODS: A prospective monocentric case-control study included 60 patients with suspected post-traumatic scapholunate ligament (SLL) tears and persistent pain. Of these, 40 patients exhibited SLL tears, subdivided into two groups of 20 each: one group with completely torn ligaments and the other with partially torn ligaments. The remaining 20 patients, whose SLLs were intact, served as controls. 4D-CT and CT arthrography were performed, and post-processed by two readers using three approaches: the standard method with full data assessment and dedicated software, partial data assessment with post-processing software (bone locking), and partial data assessment without post-processing software (no bone locking). The scapholunate gap (SLG) parameter was measured in millimeters to evaluate scapholunate diastasis during radioulnar deviation (RUD). The scapholunate ligament status on CT arthrography was considered the gold standard. RESULTS: The SLG-derived parameters (range, mean, and maximal values) were significantly increased in patients with both intact and torn scapholunate ligaments across all post-processing approaches (P values ranging from 0.001 to 0.004). SLG range was the best parameter for diagnosing SLL tears, with ROC AUC values ranging from 0.7 to 0.88 across the three post-processing methods. The interobserver reproducibility was better with the alternative approaches (ICC values 0.93-0.96) compared to the standard approach (ICC values 0.65-0.72). Additionally, post-processing time was shorter with the alternative approaches, especially when specific software was not used (reduced from 10 to three minutes). CONCLUSION: Simpler approaches to wrist 4D-CT data analysis yielded acceptable diagnostic performances and improved interobserver reproducibility compared to the standard approach.