Recalculated Dose Distributions Research Articles

Total marrow lymphoid irradiation IMRT treatment using a novel CT-linac

BackgroundA novel CT-linac (kilovolt fan-beam CT-linac) has been introduced into total marrow and lymphoid irradiation (TMLI) treatment. Its integrated kilovolt fan-beam CT (kV FBCT) can be used not only for image guidance (IGRT) but also to re-calculate the dose.PurposeThis study reported our clinical routine on performing TMIL treatment on the CT-linac, as well as dose distribution comparison between planned and re-calculated based on IGRT FBCT image sets.Methods11 sets of data from 5 male and 6 female patients who had underwent the TMLI treatment with uRT-linac 506c were selected for this study. The planning target volumes consist of all skeletal bones exclusion of the mandible and lymphatic sanctuary sites. A planned dose of 10 Gy was prescribed to all skeletal bones exclusion of the mandible in two fractions and 12 Gy in two fractions was prescribed to lymphatic sanctuary sites. Each TMLI plan contained two sub-plans, one dynamic IMRT for the upper body and the other VMAT for the lower extremity. Two attempts were made to obtain homogeneous dose in the overlapping region, i.e., applying two plans with different isocenters for the treatment of two fractions, and using a dose gradient matching scheme. The CT scans, including planning CT and IGRT FBCT, were stitched to a whole body CT scan for dose distribution evaluation.ResultsThe average beam-on time of Planupper is 30.6 min, ranging from 24.9 to 37.5 min, and the average beam-on time of Planlower is 6.3 min, ranging from 5.7 to 8.2 min. For the planned dose distribution, the 94.79% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 94.68% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). For the re-calculated dose distribution, the 92.17% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 90.07% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). The results showed that there is a significant difference (p < 0.05) between planning V10, V12 and delivery V10, V12. There is no significant difference (p > 0.05) between planned dose and re-calculated dose on selected organs, except for right lens (p < 0.05, Dmax). The actual delivered maximum dose of right lens is apparently larger than the planned dose of it.ConclusionTMLI treatment can be performed on the CT-linac with clinical acceptable quality and high efficiency. Evaluation of the recalculated dose on IGRT FBCT suggests the treatment was delivered with adequate target coverage.

Machine Log File and Calibration Errors-based Patient-specific Quality Assurance (QA) for Volumetric Modulated Arc Therapy (VMAT).

Dose reconstructed based on linear accelerator (linac) log-files is one of the widely used solutions to perform patient-specific quality assurance (QA). However, it has a drawback that the accuracy of log-file is highly dependent on the linac calibration. The objective of the current study is to represent a new practical approach for a patient-specific QA during Volumetric modulated arc therapy (VMAT) using both log-file and calibration errors of linac. A total of six cases, including two head and neck neoplasms, two lung cancers, and two rectal carcinomas, were selected. The VMAT-based delivery was optimized by the TPS of Pinnacle^3 subsequently, using Elekta Synergy VMAT linac (Elekta Oncology Systems, Crawley, UK), which was equipped with 80 Multi-leaf collimators (MLCs) and the energy of the ray selected at 6 MV. Clinical mode log-file of this linac was used in this study. A series of test fields validate the accuracy of log-file. Then, six plans of test cases were delivered and log-file of each was obtained. The log-file errors were added to the corresponding plans through the house script and the first reconstructed plan was obtained. Later, a series of tests were performed to evaluate the major calibration errors of the linac (dose-rate, gantry angle, MLC leaf position) and the errors were added to the first reconstruction plan to generate the second reconstruction plan. At last, all plans were imported to Pinnacle and recalculated dose distribution on patient CT and ArcCheck phantom (SUN Nuclear). For the former, both target and OAR dose differences between them were compared. For the latter, γ was evaluated by ArcCheck, and subsequently, the surface dose differences between them were performed. Accuracy of log-file was validated. If error recordings in the log file were only considered, there were four arcs whose proportion of control points with gantry angle errors more than ± 1°larger than 35%. Errors of leaves within ± 0.5 mm were 95% for all arcs. The distinctness of a single control point MU was bigger, but the distinctness of cumulative MU was smaller. The maximum, minimum, and mean doses for all targets were distributed between -6.79E-02-0.42%, -0.38-0.4%, 2.69E-02-8.54E-02% respectively, whereas for all OAR, the maximum and mean dose were distributed between -1.16-2.51%, -1.21-3.12% respectively. For the second reconstructed dose: the maximum, minimum, and mean dose for all targets was distributed between 0.0995~5.7145%, 0.6892~4.4727%, 0.5829~1.8931% separately. Due to OAR, maximum and mean dose distribution was observed between -3.1462~6.8920%, -6.9899~1.9316%, respectively. Patient-specific QA based on the log-file could reflect the accuracy of the linac execution plan, which usually has a small influence on dose delivery. When the linac calibration errors were considered, the reconstructed dose was closer to the actual delivery and the developed method was accurate and practical.

How much rotational error is clinically acceptable for single-isocenter/two-lesion lung SBRT treatment on halcyon ring delivery system (RDS)?

SBRT treatment of two separate lung lesions via single-isocenter/multi-target (SIMT) plan on Halcyon RDS could improve patient comfort, compliance, patient throughput, and clinic efficiency. However, aligning two separate lung lesions synchronously via a single pre-treatment CBCT scan on Halcyon can be difficult due to rotational patient setup errors. Thus, to quantify the dosimetric impact, we simulated loss of target(s) coverage due to small, yet clinically observable rotational patient setup errors on Halcyon for SIMT treatments. Seventeen previously treated 4D-CT based SIMT lung SBRT patients with two separate lesions (total 34 lesions, 50Gy in five fractions to each lesion) on TrueBeam (6MV-FFF) were re-planned on Halcyon (6MV-FFF) using a similar arc geometry (except couch rotation), dose engine (AcurosXB algorithm), and treatment planning objectives. Rotational patient setup errors of [±0.5⁰ to ±3.0⁰] on Halcyon were simulated via Velocity registration software in all three rotation axes and recalculated dose distributions in Eclipse treatment planning system. Dosimetric impact of rotational errors was evaluated for target coverage and organs at risk (OAR). Average PTV volume and distance to isocenter were 23.7 cc and 6.1cm. Average change in Paddick's conformity indexes were less than -5%, -10%, and -15% for 1°, 2°, and 3°, respectively for yaw, roll, and pitch rotation directions. Maximum drop off of PTV(D100%) coverage for 2° rotation was -2.0% (yaw), -2.2% (roll), and -2.5% (pitch). With ±1° rotational error, no PTV(D100%) loss was found. Due to anatomical complexity: irregular and highly variable tumor sizes and locations, highly heterogenous dose distribution, and steep dose gradient, no trend for loss of target(s) coverage as a function of distance to isocenter and PTV size was found. Change in maximum dose to OAR were acceptable per NRG-BR001 within ±1.0° rotation, but were up to 5Gy higher to heart with 2° in the pitch rotation axis. Our clinically realistic simulation results show that rotational patient setup errors up to 1.0° in any rotation axis could be acceptable for selected two separate lung lesions SBRT patients on Halcyon. Multivariable data analysis in large cohort is ongoing to fully characterize Halcyon RDS for synchronous SIMT lung SBRT.

Retrospective Analysis of Replan Frequency and Causes in Esophageal Cancer Patients Treated with Spot Scanned Proton Therapy

<h3>Purpose/Objective(s)</h3> For patients with esophageal cancer treated with intensity-modulated proton therapy (IMPT) at our institution, weekly verification CT scans are obtained to ensure that the plan is still acceptable. If unacceptable deviations from the intended dose are observed, replanning is performed. This study aims to investigate the frequency and causes of replans to determine the appropriate frequency of performing verification scans. <h3>Materials/Methods</h3> Data from a cohort of 205 esophageal cancer patients treated with IMPT between 2015 and 2020 were retrospectively analyzed. Patients were typically positioned head first supine with arms up in a vacuum immobilization device, and a four-dimensional CT (4DCT) simulation scan was obtained. The typical prescription was 50 Gy in 25 fractions over 5 weeks, with contours delineated as per consensus guidelines. For tumor motion ≤ 10 mm, patients were treated free-breathing with isolayer repainting, while for motion > 10 mm, gating was also added. Two posterior oblique beams were typically used, and single field optimization was performed. Robust optimization was utilized with 5-mm translational perturbations and 3% range uncertainty, with dose evaluation, also performed on the extreme respiratory phases. Weekly 4DCT verification scans in treatment position were acquired. Rigid image registration to the original planning CT image set was performed, and the care team reviewed the recalculated dose distributions to determine the need for replan. CTV (V95%) % was selected as a metric to compare the difference in target volume dose between verification scans that did [CTV_replan (V95%) %], versus did not [CTV_no-replan (V95%) %], lead to a replan. <h3>Results</h3> The primary tumor location was upper/middle esophagus (16%) or lower/gastroesophageal junction (83%). 21 patients (10%) required replanning, including 3 patients with 2 replans. Replans occurred during the 1^st (20%), 2^nd (33%), 3^rd (20%), or 4^th (25%) weeks of treatment. Primary reasons for replanning were a superior shift of the diaphragm baseline position affecting the range of the beams entering near this interface (46%), changes in tumor size or position (17%), new or resolving pleural effusion affecting the range of beams (13%), changes in stomach filling affecting the target geometry (13%), and patient setup reproducibility issues (13%). The average value of CTV_no-replan (V95%) % = 98% ± 3% vs. CTV_replan (V95%) % = 96% ± 1%. The modest size of this difference suggests that other factors, including poor fidelity of rigid CTV contours, also contribute to clinical decision-making. <h3>Conclusion</h3> In this large cohort of patients with esophageal cancer treated with robustly planned IMPT, the rate of adaptive replanning was 10% and resulted from 5 discrete changes as described above. Every other week frequency of verification scans should be considered.

A prediction model for dosimetric-based lung adaptive radiotherapy.

Anatomical changes occurred during the treatment course of radiation therapy for lung cancer patients may introduce clinically unacceptable dosimetric deviations from the planned dose. Adaptive radiotherapy (ART) can compensate these dosimetric deviations in subsequent treatments via plan adaption. Determining whether and when to trigger plan adaption during the treatment course is essential to the effectiveness and efficiency of ART. In this study, we aimed to develop a prediction model as an auxiliary decision-making tool for lung ART to identify the patients with intrathoracic anatomical changes that would potentially benefit from the plan adaptions during the treatment course. Seventy-one pairs of weekly cone-beam computer tomography (CBCT) and planning CT (pCT) from 17 advanced non-small cell lung cancer patients were enrolled in this study. To assess the dosimetric impacts brought by anatomical changes observed on each CBCT, dose distribution of the original treatment plan on the CBCT anatomy was calculated on a virtual CT generated by deforming the corresponding pCT to the CBCT and compared to that of the original plan. A replan was deemed needed for the CBCT anatomy once the recalculated dose distribution violated our dosimetric-based trigger criteria. A three-dimensional region of significant anatomical changes (region of interest, ROI) between each CBCT and the corresponding pCT was identified, and 16 morphological features of the ROI were extracted. Additionally, eight features from the overlapped volume histograms (OVHs) of patient anatomy were extracted for each patient to characterize the patient-specific anatomy. Based on the 24 extracted features and the evaluated replanning needs of the pCT-CBCT pairs, a nonlinear supporting vector machine was used to build a prediction model to identify the anatomical changes on CBCTs that would trigger plan adaptions. The most relevant features were selected using the sequential backward selection (SBS) algorithm and a shuffling-and-splitting validation scheme was used for model evaluation. Fifty-five CBCT-pCT pairs were identified of having an ROI, among which 21 CBCT anatomies required plan adaptions. For these 21 positive cases, statistically significant improvements in the sparing of lung, esophagus and spinal cord were achieved by plan adaptions. A high model performance of 0.929 AUC (area under curve) and 0.851 accuracy was achieved with six selected features, including five ROI shape features and one OVH feature. Without involving the OVH features in the feature selection process, the mean AUC and accuracy of the model significantly decreased to 0.826 and 0.779, respectively. Further investigation showed that poor prediction performance with AUC of 0.76 was achieved by the univariate model in solving this binary classification task. We built a prediction model based on the features of patient anatomy and the anatomical changes captured by on-treatment CBCT imaging to trigger plan adaption for lung cancer patients. This model effectively associated the anatomical changes with the dosimetric impacts for lung ART. This model can be a promising tool to assist the clinicians in making decisions for plan adaptions during the treatment courses.

Comparison of pre-treatment and in-vivo dosimetry for advanced radiotherapy of prostate cancer.

BackgroundThe usage of advanced radiotherapy techniques requires validation of a previously calculated dose with the precise delivery with a linear accelerator. This study aimed to review and evaluate new verification methods of dose distribution. Moreover, our purpose was to define an internal protocol of acceptance for in-vivo measurements of dose distribution.Materials and methodsThis study included 43 treatment plans of prostate cancer calculated using the Monte Carlo algorithm. All plans were delivered using the Volumetric Modulated Arc Therapy (VMAT) technique of advanced radiotherapy by the linear accelerator Elekta VersaHD. The dose distribution was verified using: MatriXX, iViewDose, and in-vivo measurements. The verification also included recalculation of fluence maps of quality assurance plans in another independent algorithm.ResultsThe acceptance criterion of 95% points of dose in agreement was found for pre-treatment verification using MatriXX; the average γ value was 99.09 ± 0.93 (SD) and 99.64 ± 0.35 (SD) for recalculation in the Collapse Cone algorithm. Moreover, using the second algorithm in the verification process showed a positive correlation ρ = 0.58, p < 0.001. However, verification using iViewDose in a phantom and in-vivo did not meet this γ-pass rate.ConclusionsEvaluation of gamma values for in-vivo measurements utilizing iViewDose software was helpful to establish an internal dosimetry protocol for prostate cancer treatments. We assumed value at a minimum of 50% points of the dose in agreement with the 3%/3 mm criterion as an acceptable compliance level. The recalculated dose distribution of QA plans in regard to the Collapse Cone algorithm in the other treatment planning system can be used as a pre-treatment verification method used by a medical physicist in their daily work. The effectiveness of use in iViewDose software, as a pre-treatment tool, is still debatable, unlike the MatriXX device.

Evaluation of Patient-Specific Quality Assurance for Carbon Ion Radiotherapy Using Full Energy Scanning Method at QST Hospital

Purpose: Patient-specific QA (PSQA) measurements for carbon ion radiotherapy (CIRT) are critical components of processes designed to identify discrepancies between calculated and delivered doses. We report the results of PSQA conducted at the QST Hospital during the period from September 2017 to March 2018. Methods: We analyzed PSQA results for 1448 fields for 10 disease sites with various target volumes, target depths and number of energy layers. For the PSQA, all the planned beams were recalculated on a water phantom with treatment planning software. The recalculated dose distributions were compared with the measured distributions using a 2D ionization chamber array at three depths, including 95% of the area of the prescription dose. These recalculated dose distributions were evaluated using the 3%/3mm gamma index with a passing threshold of 90%. Results: The passing rates for prostate, head and neck, and bone and soft tissue were 96.8%, 99.3%, and 91.7%, respectively. Additionally, 94.7% of lung plans with low energy beams passed. Overall, the CIRT in the QST Hospital reached a high passing rate of more than 95%. Although the remaining 5% failed to pass, there was no dependence between measurement depth and disease sites in these failures. Conclusion: Using PSQA measurements, we confirmed consistency between the planned and delivered doses for CIRT using the full energy scanning method.

The effects of rotational setup errors in total body irradiation using helical tomotherapy.

PurposeHelical tomotherapy (HT) is a form of intensity‐modulated radiation therapy that is employed in total body irradiation (TBI). Because TBI targets the whole body, accurate setup positioning at the edge of the treatment volume is made difficult by the whole‐body rotational posture. The purpose of this study is to clarify the tolerance for rotational setup error (SE) in the vertical direction. In addition, we perform a retrospective analysis of actually irradiated dose distributions using previous patients’ irradiation data.MethodsTo clarify the effects of rotational SE on the dose distribution, the planned CT images of 10 patients were rotated by 1–5° in the vertical (pitch) direction to create a pseudo‐rotational SE image. Then, the effect of the magnitude of the rotational SE on the dose distribution was simulated. In addition, the irradiated dose to the patients was analyzed by obtaining recalculated dose distributions using megavoltage CT images acquired before treatment.ResultsThe simulation results showed that the average value of the lung volume receiving at least 10 Gy did not exceed the allowable value when the SE value was ≤2°. When the rotational SE was ≤3°, it was possible to maintain the clinical target volume dose heterogeneity within ±10% of the prescribed dose, which is acceptable according to the guidelines. A retrospective analysis of previous patients’ irradiation data showed their daily irradiation dose distribution. The dose to the clinical target volume was reduced by up to 3.4% as a result of the residual rotational SE. Although whole‐course retrospective analyses showed a statistically significant increase in high‐dose areas, the increase was only approximately 1.0%.ConclusionsDose errors induced by rotational SEs of ≤2° were acceptable in this study.

An approach for estimating dosimetric uncertainties in deformable dose accumulation in pencil beam scanning proton therapy for lung cancer

Deformable image registration (DIR) is an important component for dose accumulation and associated clinical outcome evaluation in radiotherapy. However, the resulting deformation vector field (DVF) is subject to unavoidable discrepancies when different algorithms are applied, leading to dosimetric uncertainties of the accumulated dose. We propose here an approach for proton therapy to estimate dosimetric uncertainties as a consequence of modeled or estimated DVF uncertainties. A patient-specific DVF uncertainty model was built on the first treatment fraction, by correlating the magnitude differences of five DIR results at each voxel to the magnitude of any single reference DIR. In the following fractions, only the reference DIR needs to be applied, and DVF geometric uncertainties were estimated by this model. The associated dosimetric uncertainties were then derived by considering the estimated geometric DVF uncertainty, the dose gradient of fractional recalculated dose distribution and the direction factor from the applied reference DIR of this fraction. This estimated dose uncertainty was respectively compared to the reference dose uncertainty when different DIRs were applied individually for each dose warping. This approach was validated on seven NSCLC patients, each with nine repeated CTs. The proposed model-based method is able to achieve dose uncertainty distribution on a conservative voxel-to-voxel comparison within ±5% of the prescribed dose to the ‘reference’ dosimetric uncertainty, for 77% of the voxels in the body and 66%–98% of voxels in investigated structures. We propose a method to estimate DIR induced uncertainties in dose accumulation for proton therapy of lung tumor treatments.

Monte Carlo evaluation of target dose coverage in lung stereotactic body radiation therapy with flattening filter-free beams.

Previous studies showed that replacing conventional flattened beams (FF) with flattening filter-free (FFF) beams improves the therapeutic ratio in lung stereotactic body radiation therapy (SBRT), but these findings could have been impacted by dose calculation uncertainties caused by the heterogeneity of the thoracic anatomy and by respiratory motion, which were particularly high for target coverage. In this study, we minimized such uncertainties by calculating doses using high-spatial-resolution Monte Carlo and four-dimensional computed tomography (4DCT) images. We aimed to evaluate more reliably the benefits of using FFF beams for lung SBRT. For a cohort of 15 patients with early stage lung cancer that we investigated in a previous treatment planning study, we recalculated dose distributions with Monte Carlo using 4DCT images. This included fifteen FF and fifteen FFF treatment plans. Compared to Monte Carlo, the treatment planning system (TPS) over-predicted doses in low-dose regions of the planning target volume. For most patients, replacing FF beams with FFF beams improved target coverage, tumor control, and uncomplicated tumor control probabilities. Monte Carlo tends to reveal deficiencies in target coverage compared to coverage predicted by the TPS. Our data support previously reported benefits of using FFF beams for lung SBRT.

Impact of changes in body contours on radiation therapy dose distribution after uterine cervical cancer surgery.

Patients receiving postoperative irradiation for uterine cervical cancer might not be able to eat during radiation therapy because of the effects of concurrent chemo-radiotherapy; this may lead to changes in the patient's body shape during treatment. When performing image-guided radiotherapy, it is necessary to determine immediately whether treatment can be performed on the day or whether re-planning is required. The purpose of this study was to determine indicators for re-planning by examining the effects of changing body contours on radiation therapy dose. The original body contour was reduced by 1cm in the front portion (structure-set 1). Based on the original dose distribution, the dose recalculation was performed with a structure set created using the body contour of structure-set 1. The difference between the original and recalculated dose distributions of structure-set 1 was evaluated through gamma analysis (GA). In the GA results for dose distribution obtained via recalculation with structure-set 1, a pass rate of 90% or more was obtained for a criterion of 2mm/2% in all cases. The results suggest that dose re-planning is rarely required when the body shape is reduced by only 1cm in the front.

Impact of interfractional anatomical variation and setup correction methods on interfractional dose variation in IMPT and VMAT plans for pancreatic cancer patients: A planning study.

PurposeTo investigate the impact of interfractional anatomical changes and setup correction methods on dose distributions in pancreatic cancer patients under breath‐hold conditions.MethodsThree intensity‐modulated proton therapy (IMPT) plans with different beam arrangements and one volumetric‐modulated arc therapy (VMAT) plan prescribing 54 Gy in 30 fractions were created for 10 patients who underwent three additional CT scans performed at an interval of 1–2 weeks. The additional CT sets were rigidly registered to the simulation CT set using both bone‐matching (BM) and organ‐matching (OM) methods in each patient. Recalculated dose distributions and dose–volume indices on the additional CT sets using either the BM or the OM method were compared with the simulation values.ResultsDifferences in the gross tumor volume D98% value from the simulation sets ranged from −0.8 to −5.9% on average. In addition, the variations were larger with OM compared with BM for two IMPT plans. Meanwhile, differences in the D98% value in the region isotropically enlarged by 5 mm from the gross tumor volume were significantly improved with OM on two IMPT plans and the VMAT plan. Among the organs at risk, the dose–volume indices were significantly improved with OM only in the duodenum on all plans.ConclusionOrgan‐matching may be a better setup correction technique than BM for both photon therapy and IMPT plans. However, in some beam arrangements of IMPT, the dose distribution may be somewhat worse using OM, due to interfractional anatomical variation. Therefore, it is important to choose beam angles that are less likely to be influenced by changes in the gastrointestinal gas volume, especially in IMPT plans.

A sparse orthogonal collimator for small animal intensity-modulated radiation therapy part I: Planning system development and commissioning.

To achieve more translatable preclinical research results, small animal irradiation needs to more closely simulate human radiotherapy. Although the clinical gold standard is intensity-modulated radiation therapy (IMRT), the direct translation of this method for small animals is impractical. In this study we describe the treatment planning system for a novel dose modulation device to address this challenge. Using delineated target and avoidance structures, a rectangular aperture optimization (RAO) problem was formulated to penalize deviations from a desired dose distribution and limit the number of selected rectangular apertures. RAO was used to create IMRT plans with highly concave targets in the mouse brain, and the plan quality was compared to that using a hypothetical miniaturized multileaf collimator (MLC). RAO plans were also created for a realistic application of mouse whole liver irradiation and for a highly complex two-dimensional (2D) dose distribution as a proof-of-principle. Beam commissioning data, including output and off-axis factors and percent depth dose (PDD) curves, were acquired for our small animal irradiation system and incorporated into the treatment planning system. A plan post-processing step was implemented for aperture size-specific dose recalculation and aperture weighting reoptimization. The first RAO test case achieved highly conformal doses to concave targets in the brain, with substantially better dose gradient, conformity, and target dose homogeneity than the hypothetical miniaturized MLC plans. In the second test case, a highly conformal dose to the liver was achieved with significant sparing of the kidneys. RAO also successfully replicated a complex 2D dose distribution with three prescription dose levels. Energy spectra for field sizes 1 to 20mm were calculated to match the measured PDD curves, with maximum and mean dose deviations of 4.47±0.30% and 1.71±0.18%. The final reoptimization of aperture weightings for the complex RAO test plan was able to reduce the maximum and mean dose deviations between the optimized and recalculated dose distributions from 10.3% to 6.6% and 4.0% to 2.8%, respectively. Using the advanced optimization techniques, complex IMRT plans were achieved using a simple dose modulation device. Beam commissioning data were incorporated into the treatment planning process to more accurately predict the resulting dose distribution. This platform substantially reduces the gap in treatment plan quality between clinical and preclinical radiotherapy, potentially increasing the value and flexibility of small animal studies.

Validation of a model for physical dose variations in irregularly moving targets treated with carbon ion beams.

In particle therapy, conventional treatment planning systems rely on an imaging representation of the irradiated region to compute the dose. For irregular breathing, when an imaging dataset describing the actual motion is not available, a different approach for dose estimation is needed. To this aim, we validate a method for the estimation of physical dose variations in gated carbon ion treatments, providing also a demonstration of the feasibility of physical dose metrics to assess the method performance. Finally, we describe a sample use case, in which this method is used to assess plan robustness with respect to undetected irregular tumor motion. The method entails the definition of a patient- and beam-specific water equivalent depth (WED) space, the simulation of motion as a translation equal to tumor displacement, and the reconstruction of the altered dose. We validated the approach using four-dimensional computed tomographies (4DCTs) and clinical plans in 12 patients, treated with respiratory gated carbon ion beams at the National Centre for Oncological Hadrontherapy (Pavia, Italy). Using the end-exhale CT and dose distribution as a reference, the physical dose delivered at the end-inhale tumor position was estimated and compared to the ground-truth dose recalculation on the end-inhale CT. Biologically effective and physical dose variations between the plan and the recalculation were compared as well. As a use case, we evaluated dose changes caused by simulated irregular tumor motion, that is, linear and nonlinear baseline shifts and/or amplitude variations with hysteresis. The ratio between biologically effective and physical equivalent uniform dose (EUD) variations due to end-exhale to end-inhale motion was less than one for 96% of investigated structures. In the validation study, we found a median error corresponding to a 14% EUD overestimation for the tumor and 4% EUD underestimation for a subgroup of organs at risk, together with a high EUD variation due to motion [median 352% EUD variation between end-exhale and end-inhale doses in the planning tumor volume (PTV)]. Considering relevant dose-volume histogram (DVH) metrics, the median difference between estimated and ground truth doses was≤4%. Gamma analysis between estimated and recalculated dose distributions resulted in a pass rate>80% for 83% of the target volumes. For the two patients selected for the sample use case, a patient-specific assessment of the method performance was performed on the 4DCT and it was possible to relate EUD variations of both tumor and organs at risk to the simulated target motion. The physical dose distribution was found to be more sensitive to motion with respect to the biologically effective one, suggesting the suitability of the physical dose metrics for the WED-space method validation. We showed that the method can compensate for intra-fractional tumor motion with proper accuracy in the selected patient group, although its use is recommended when limited deformations are expected. In conclusion, the WED-space method can provide simulations of dose alteration due to irregular breathing when imaging data are lacking, and, once integrated with relative biological effectiveness (RBE) modeling, it would be useful in evaluating the robustness of carbon ion treatment plans.

On-line dose-guidance to account for inter-fractional motion during proton therapy.

Background and purposeProton therapy (PT) of extra-cranial tumour sites is challenged by density changes caused by inter-fractional organ motion. In this study we investigate on-line dose-guided PT (DGPT) to account inter-fractional target motion, exemplified by internal motion in the pelvis.Materials and methodsOn-line DGPT involved re-calculating dose distributions with the isocenter shifted up to 15 mm from the position corresponding to conventional soft-tissue based image-guided PT (IGPT). The method was applied to patient models with simulated prostate/seminal vesicle target motion of ±3, ±5 and ±10 mm along the three cardinal axes. Treatment plans were created using either two lateral (gantry angles of 90°/270°) or two lateral oblique fields (gantry angles of 35°/325°). Target coverage and normal tissue doses from DGPT were compared to both soft-tissue and bony anatomy based IGPT.ResultsDGPT improved the dose distributions relative to soft-tissue based IGPT for 39 of 90 simulation scenarios using lateral fields and for 50 of 90 scenarios using lateral oblique fields. The greatest benefits of DGPT were seen for large motion, e.g. a median target coverage improvement of 13% was found for 10 mm anterior motion with lateral fields. DGPT also improved the dose distribution in comparison to bony anatomy IGPT in all cases. The best strategy was often to move the fields back towards the original target position prior to the simulated target motion.ConclusionDGPT has the potential to better account for large inter-fractional organ motion in the pelvis than IGPT.

OA012] Differences between real and planned dose distributions as a result of uncorrected patient rotation in radiotherapy

Purpose To study the influence of relatively small and uncorrected rotational errors in patient positioning on the dose distribution for Head and Neck and Brain cases. Methods Analysis was carried out for 15 Head and Neck and Brain patients irradiated with VMAT technique. Cone beam CT (CBCT), which was performed for every patient in five to seven fractions during the treatment course, was only used for correcting patient shift. Rotational patient positioning errors were not corrected since it is not possible at most of radiotherapy departments. After the whole course, additional offline registrations of originally acquired CBCT with planning CTs were performed and rotational errors for pitch, roll and yaw (rx, ry, rz) were obtained. Only cases, where errors in patient rotation could not be partially compensated with table shift, were used for this analysis. For every patient, mean rotational corrections were determined. Planning CTs were rotated in all three axes according to the detected mean rotational corrections for individual patients and the original dosimetry plans were recalculated into the rotated CT. The recalculated plans were then used to evaluate the maximum dose to brainstem, optic nerve and chiasma. Results The highest mean rotational positioning errors were found on the X-axis, where the mean rotational error rx was 1,17° (0,20° to 1,98°). For Y and Z-axes the mean rotational errors ry and rz were 0,80° (0,33° to 1,60°) and 0,74° (0,10° to 1,65°), respectively. Recalculated dose distributions in rotated CTs were compared to those in original planning CTs. For all patients maximum doses to brainstem, chiasma and optic nerve were higher in recalculated plans with the mean increase of 0,8 Gy (0,1 to 1,5 Gy), 2,4 Gy (0,3 to 4,3 Gy) and of 2,5 Gy (0,2 to 5,2 Gy), respectively. Conclusions Uncorrected rotational errors for Head and Neck and Brain cases can substantially increase the maximum doses to critical structures. As the dose limits of chiasma (for two patients) and optic nerve (for one patient) were exceeded, the recalculated dose distributions would be evaluated as clinically unacceptable.

P203] WEPL-corrected margins for moving targets in carbon-ion gated treatments: Preliminary results

Purpose To evaluate intra- and inter-fractional robustness of carbon-ion treatment plans based on water-equivalent path length (WEPL) corrected ITV margins for moving targets irradiated with gated pencil-beam scanning. Methods As a preliminary study, three patients with thoraco-abdominal targets were considered. Clinical plans were optimized with an Intensity Modulated Particle Therapy (IMPT) algorithm and the use of case-specific avoidance structures to prevent radiation pathways on regions subject to intra- and inter-fractional variations. Plans were optimized on the end-exhale CT of a 4DCT dataset using 2 fields and tested for consistency within the gating window by recalculation on the 30%-exhale and 30%-inhale CTs. Single Field Uniform Dose (SFUD) plans were optimized on beam-specific WEPL-corrected ITV ( ITV WEPL ), which comprised the envelope of water-equivalent target positions within the ideal gating window. Differently from clinical plans, avoidance structures were not used in this approach. Clinical plans were taken as reference for comparison. Dose recalculations on the planning 4DCT and on synthetic 4DCT simulating irregular breathing allowed to evaluate intra-fractional robustness of the two approaches, whereas inter-fractional robustness was estimated on re-evaluation CTs (one per patient). Differences in the conformity index CI = V 95 % / V target , target coverage D 95 % and homogeneity index HI = ( D 2 % − D 98 % )/ D 50 % between the end-exhale plan and the recalculated dose distributions were computed. Doses to the involved organs at risk (OARs) were evaluated as well. Results The CI presented slightly higher median intra-/inter-fractional variations and absolute values in the ITV WEPL approach (13%–1.47) with respect to reference plans (6%–1.36). D 95 % and HI showed lower median intra-fractional variations for the ITV WEPL approach (0.1% and 35%) compared to reference plans (3.4% and 46%). In case of inter-fractional changes, the use of ITV WEPL led to higher median variations but comparable absolute values for D 95 % (3.8% vs 2.2%) and for HI (144% vs 20%, absolute median values: 0.11 vs 0.14). The two methods performed similarly in OARs. Conclusions The use of WEPL-corrected ITV permits adequate tumor coverage even in presence of irregular breathing motion, for the small analyzed sample. Although uncertainties due only to intra-fractional organ motion were considered in the ITV WEPL approach, comparable inter-fractional robustness was found among the two strategies.

P165] Analysis of dose deposition in lung lesions: A modified PTV for a robust optimization

Purpose SBRT in lung cancer delivers high doses to a small dense nodule (GTV) moving into a low density tissue. If an IMRT-VMAT technique is used, an apparently homogeneous dose is delivered, but an high photon fluence is generated inside the PTV-GTV shell due to its low electron density (ED). This gives the paradox that the dose distribution seems uniform, but the GTV, which moves into the PTV, will receive a dose depending on its position. Methods A TPS ”Monaco” (MC algorithm) was used to simulate a dummy patient (55 Gy in 5 fractions). In step 1, in order to evaluate the dose discrepancy on the target when the motion of the GTV is considered, the photon fluence was optimized for the original PTV ED (EDo) and thus used to calculate the dose on a “forced” PTV ED (EDf), in which the ED of the PTV was forced to the mean ED of the GTV. In step 2, the photon fluence was optimized for PTV EDf and then used for dose calculation on PTV EDo to evaluate the dose variation on the lower ED region of the PTV and inside the GTV. Dosimetric comparisons between the original and the recalculated dose distribution for PTV-GTV were made in terms of: dose profiles, Dmean, D98% and D2%. Results In step 1 dose profiles differ up to 6.6%, 3.4% and 3.8% on longitudinal, sagittal and transversal axes along the isocenter. Increments of 1.6% for D98%, 2.5% for Dmean and 5% for D2% were obtained for PTV-GTV. In step 2 differences between dose profiles were −3% for all. A reductions of −1.5% for D98%, −1.5% for Dmean and −1.4% for D2% were achieved for PTV-GTV. Conclusions Step 1 shows that the dose delivered to GTV, when it moves where the photon fluence is optimized for lower ED, is higher than what estimated on the original EDo. The GTV is irradiated in a more homogeneous way in step 2 in which the fluence is optimized for EDf. We propose to modify the PTV electron density thus considering the GTV mobility, and evaluating more effectively the actual GTV dose.

Field Shape Optimization Technique Based on Dose Volume Histogram Using Daily Cone-beam Computed Tomography in Three-dimensional Conformal Radiation Therapy for Localized Prostate Cancer: Develop and Evaluation

This study aimed to develop and evaluate field shape optimization technique based on dose calculation using daily cone-beam computed tomography (CBCT) to compensate for interfractional anatomic changes in three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer. For each of 10 patients, 9-10 CBCT images were obtained throughout the treatment course. The prostate, seminal vesicles, and rectum were manually contoured in all CBCT images. Subsequently, plan adaptation was performed with a program developed in-house. This program calculates dose distributions on CBCT images and optimizes field shape to minimize rectal dose while keeping the target at the optimal dose coverage (the planning target volume D95% receives 95% of the prescription dose). To evaluate the adaptive planning approach, we re-calculated dose distributions on CBCT images based on the conventional and adaptive plans. For the entire cohort, plan adaptation improved rectal V50 Gy, V60 Gy, V65 Gy, and V70 Gy by -7.71±8.43%, -8.30±8.90%, -7.91±8.51% and -7.03±7.70% on average (±SD), respectively. Our results demonstrate that adaptive planning approach is superior to the conventional planning approach for optimizing dose distribution, and this adaptive approach can optimize field shape in 3 min. The proposed approach can be an effective solution for the problem of interfractional anatomic changes in 3D-CRT for prostate cancer.

Intrafractional Prostate Motion and Dose Variation during Radiation Therapy for Prostate Cancer Using 4D-TPUS

More recently, noninvasive 4D transperineal ultrasound (4D-TPUS) has been introduced in tracking intrafractional prostate motion in radiotherapy. Compared to other tracking method, the ultrasound has its own advantage in precise identification of soft tissue without invasive procedure or extra radiation dose. In this study, we investigated the prostate motion model and dose variation during radiotherapy using a transperineal autoscan ultrasound system (Clarity®, Elekta Inc., Sweden). From July 2014 through December 2016, 57 prostate cancer patients were enrolled with a median age of 74 years (range 61-85). All patients were asked to have a full bladder and empty rectum before each treatment. A simultaneous CT and TPUS simulation was conducted to provide a fused CT/US reference. Before radiation delivery, prostates were localized using CBCT to determine setup offsets relative to the patients’ skin tattoos. During the treatment, real-time ultrasound images were acquired and data was collected for direct monitoring of 3D motion of the prostate. Then dose distributions were recalculated with the isocenter shifts relative to the simulation CT images according to the real-time data using the leaf sequences/MUs based on the original treatment plan. The doses were compared with the original doses planned on the simulation CT using the clinical acceptance criteria. A total of 1207 fractions were evaluated. The mean (±SD) of the infraction displacements were [mm]: I(+)/S: (0.03 ± 0.92); L(+)/R: (0.12 ± 1.03); and A(+)/P: (-0.01 ± 1.37), respectively. There were 41/1207 (3.4%), 29/1207 (2.4%), and 66/1207 (5.5%) fractions with deviation exceeded 3 mm in the IS, LR, and AP directions, respectively. The A/P direction has the largest extent of prostate displacement. The percentage of time with displacements 0-1mm, 1-2mm, 2-3mm and larger than 3 mm was 88.1%, 9.8%, 1.7% and 0.4% in the IS direction, 89.3%, 8.9%, 1.5% and 0.3 % in the LR direction, 84.5%, 11.1%, 3.7%, and 0.7% in the AP direction. We classified our patients into three groups according to the motion model: stable (n=50), irregular (n=3) and intention (n=4). The intention group was defined as persistent deviation to the same direction (the maximal displacement should exceed 3 mm) that repeated in at least 50% fractions. All these patients had obviously anxiety and urinary frequency and/or urgency. Recalculated dose distributions showed that all the 4 patients in the intention group did not meet our criterion of D95% of PTV prostate> 8000 cGy or V70 of rectum< 20%, which may leading to insufficient treatment and increased toxicity. The present study demonstrated that for over 90% of fractions, a CTV-PTV margin of 3 mm would be good coverage with the planned prescribed dose. However, it is important to identify the patients belonging to the intention group. Pre-treatment with anti-anxiety drugs and α receptor blocker may be useful in relief the prostate motion.