Assessment and validation of glottic motion using cone-beam CT and real-time cine MRI.

PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.

A retrospective multi-center feasibility study of a new PTV margin estimation approach for moving targets using CyberKnife log files.

PURPOSE: This study investigates a new approach for estimating the planning target volume (PTV) margin for moving tumors treated with robotic stereotactic body radiotherapy (SBRT). METHODS: In this new approach, the covariance of modeling and prediction errors was estimated using error propagation and implemented in the Van Herk formula to form a Modified Van Herk formula (MVHF). To perform a retrospective multi-center analysis, the MVHF was studied using 163 patients treated with different system versions of robotic SBRT (G3 version 6.2.3, VSI version 8.5, and VSI version 9.5) and compared with two established PTV margins estimation methods: The original Van Herk Formula (VHF) and the Uncertainty Estimation Method (UEM). RESULTS: Overall, the PTV margins provided by the three formalisms are similar with 4-5 mm in the lung region and 4 mm in abdomen region to the PTV margins used in clinical. Furthermore, when analyzing individual patients, a difference of up to 1 mm was found between the PTV margin estimations using MVHF and VHF. The corresponding average discrepancies for the superior-inferior (SI) direction ranged between -0.19 mm to 0.38 mm in CK G3 version 6.2.3, -0.36 mm to 0.33 mm in CK VSI version 8.5, and -0.34 mm to 0.40 mm in CK VSI version 9.5. CONCLUSIONS: It was found that for the lower left lung, upper left lung, lower right lung, upper right lung, central liver, and upper liver, the effect of covariance between model and prediction errors in SI direction was around 20%, 30%, 25%, 25%, 25%, and 30%, respectively. Notable covariance effects between model and prediction errors can be considered in PTV margin estimation using a modified VHF, which allowed for more precise target localization in robotic SBRT for moving tumors. Overall, in each of the three directions, the difference between MVHF and utilized clinical margins is 0.65 mm in the lung and abdominal region. Therefore, to improve the clinical PTV margins with the new approach, it is suggested to use the adaptive PTV margins in the next fractions.

Radiation-induced prostate swelling during SBRT of the prostate.

BACKGROUND: Reduced planning target volume (PTV) margins are commonly used in stereotactic body radiotherapy (SBRT) of the prostate. In addition, MR-only treatment planning is becoming more common in prostate radiotherapy and compared to CT-MRI-based contouring results in notable smaller clinical target volume (CTV). Tight PTV margins coupled with MR-only planning raise a concern whether the margins are adequate enough to cover possible volumetric changes of the prostate. The aim of this study was to evaluate the volumetric change of the prostate and its effect on PTV margin during 5x7.25 Gy SBRT of the prostate. MATERIAL AND METHODS: Twenty patients were included in the study. Three MRI scans, first prior to treatment (baseline), second after third fraction (mid-treatment) and third after fifth fraction (end-treatment) were acquired for each patient. Prostate contours were delineated on each MRI scan and used to assess the prostate volume and maximum prostate diameter on left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions at baseline, mid- and end-treatment. RESULTS: Median (IQR) change in the prostate volume relative to the baseline was 12.0% (3.1, 17.7) and 9.2% (2.0, 18.9) at the mid- and end-treatment, respectively, and the change was statistically significant (p = 0.004 and p = 0.020, respectively). Compared to the baseline, median increase in the maximum LR, SI and AP prostate diameters were 0.8, 2.3 and 1.5 mm at mid-treatment, and 0.5, 2.5 and 2.3 mm at end-treatment, respectively. CONCLUSION: If prostate contouring is based solely on MRI (e.g., in MR-only protocol), additional margin of 1-2 mm should be considered to account for prostate swelling. The study is part of clinical trial NCT02319239.

Target margin design through analyzing a large cohort of clinical log data in the cyberknife system.

PURPOSE: Calculating the adequate target margin for real-time tumor tracking using the Cyberknife system is a challenging issue since different sources of error exist. In this study, the clinical log data of the Cyberknife system were analyzed to adequately quantify the planned target volume (PTV) margins of tumors located in the lung and abdomen regions. METHODS: In this study, 45 patients treated with the Cyberknife module were examined. In this context, adequate PTV margins were estimated based on the Van Herk formulation and the uncertainty estimation method by considering the impact of errors and uncertainties. To investigate the impact of errors and uncertainties on the estimated PTV margins, a statistical analysis was also performed. RESULTS: Our study demonstrates five different sources of errors, including segmentation, deformation, correlation, prediction, and targeting errors, which were identified as the main sources of error in the Cyberknife system. Furthermore, the clinical evaluation of the current study reveals that the two different formalisms provided almost identical PTV margin estimates. Additionally, 4-5 mm and 5 mm margins on average could provide adequate PTV margins at lung and abdomen tumors in all three directions, respectively. Overall, it was found that concerning the PTV margins, the impact of correlation and prediction errors is very high, while the impact of robotics error is low. CONCLUSIONS: The current study can address two limitations in previous researches, namely insufficient sample sites and a smaller number of patients. A comparison of the present results concerning the lung and abdomen areas with other studies reveals that the proposed strategy could provide a better reference in selection the PTV margins. To our knowledge, this study is one of the first attempts to estimate the PTV margins in the lung and abdomen regions for a large cohort of patients treated using the Cyberknife system.

The effectiveness and safety of direct-acting antivirals for hepatitis C virus treatment: A single-center experience in Saudi Arabia.

Background: The introduction of direct-acting antivirals (DAA) to treat the hepatitis C virus (HCV) overcame many drawbacks of interferon-based therapy. DAA achieved sustained viral response (SVR) rates above 90% and overcame many drawbacks of pegylated interferon regimens.The HCV genotype (GT) distribution varies by geographical area, with GT-4 being most prevalent in the Middle East region, including Saudi Arabia. Yet, the real-world evidence about using DAAs in the Saudi population is limited.Thus, the aim of this study to investigate the effectiveness and safety of DAAs in Saudi patients with HCV infection. Methods: A retrospective cohort study included patients treated with DAAs from 2015 to 2017 at a tertiary care hospital in Riyadh, Saudi Arabia. All patients with HCV treated with either ledipasvir plus sofosbuvir (LDS/SOF) ± ribavarin (RBV) or ombitasvir-paritaprevir-ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± RBV were included. Using a per-protocol analysis, the effectiveness outcome was the end-of-treatment response (EOTr) and Sustained virologic reponce12 weeks after competing the regimen (SVR12). The secondary safety outcome was the adverse event related to the therapy reported by the patients. Results: A total of 97 patients were included; with the majority infected with GT-4 (64 %), followed by GT-1 (18 %), in addition to 8 % having a mixed GT (1 + 4). The EOTr and SVR12 rates were 98 % and 96 %, respectively. SVR12 was 94.4 % within the LDS/SOF ± RBV group and 97.7 % within the OBV/PTV/r ± DSV ± RBV group. Only 4 % had a response failure due to relapse or breakthrough, and all were infected with mixed GT1 + 4. Medications were well tolerated with minimal side effects, including vomiting, nausea, and weakness. Conclusion: DAAs regimens are associated with high rates of SVR12 and are well tolerated with a good safety profile in Saudi HCV-infected patients.

Impact of immobilisation and image guidance protocol on planning target volume margins for supine craniospinal irradiation.

Background: The setup errors during supine-CSI (sCSI) using single or dual immobilisation (SM, DM) subsets from two institutions were reviewed to determine if DM consistently decreased the required planning target volumes (PTV) margins and to identify the optimal image guidance environments. Materials and methods: Ours and a sister institutional cohort, each with a subset of SM or DM sCSI and daily 3-dimensional online image verification sets, were reviewed for the cranial and spinal regions translational shifts. Using descriptive statistics, scatter plots and independent sample Mann-Whitney test we compared shifts in each direction for two subsets in each cohort deriving PTV margins (Van Herk: VH, Strooms: St recipes) for the cranial and spinal regions. Three image guidance (IG) protocols were simulated for two regions on the combined cohort with SM and DM subsets to identify the most optimal option with the smallest PTV margin. The IG protocols: 3F, 5F and 5FB where the systematic error correction was done using the average error from the first three, five and in the cranium alone (applied to both the cranium and spine, otherwise) for the first five set-ups, respectively. Results: 6968 image sets for 179 patients showed DM could consistently reduce the PTV margin (VH/St) for the cranium from 6/5 to 4/3.5 (31.8/30.8%) and 6/4 to 4/3.5 mm (30.5/16.8%) for primary and validation cohort, respectively. Similarly, for the spine it was 10/8.5 to 6/5.5 (38.6/38.4%) and 9/7.7 to 7/6 (21.6/21.4%), respectively. The "5F-IG" resulted in the smallest margins for both the cranial (3 mm) and spinal region (5 mm) for DM with estimated 95% CTV coverage probability. Conclusion: DM with 5F-IG would significantly reduce the required PTV margins for sCSI.

Automated algorithm for calculation of setup corrections and planning target volume margins for offline image-guided radiotherapy protocols.

PURPOSE: Each radiotherapy center should have a site-specific planning target volume (PTV) margins and image-guided (IG) radiotherapy (IGRT) correction protocols to compensate for the geometric errors that can occur during treatment. This study developed an automated algorithm for the calculation and evaluation of these parameters from cone beam computed tomography (CBCT)-based IG-intensity modulated radiotherapy (IG-IMRT) treatment. METHODS AND MATERIALS: A MATLAB algorithm was developed to extract the setup errors in three translational directions (x, y, and z) from the data logged by the CBCT system during treatment delivery. The algorithm also calculates the resulted population setup error and PTV margin based on the van Herk margin recipe and subsequently estimates their respective values for no action level (NAL) and extended no action level (eNAL) offline correction protocols. The algorithm was tested on 25 head and neck cancer (HNC) patients treated using IG-IMRT. RESULTS: The algorithms calculated that the HNC patients require a PTV margin of 3.1, 2.7, and 3.2 mm in the x-, y-, and z-direction, respectively, without IGRT. The margin can be reduced to 2.0, 2.2, and 3.0 mm in the x-, y-, and z-direction, respectively, with NAL and 1.6, 1.7, and 2.2 mm in the x-, y-, and z-direction, respectively, with eNAL protocol. The results obtained were verified to be the same with the margins calculated using an Excel spreadsheet. The algorithm calculates the weekly offline setup error correction values automatically and reduces the risk of input data error observed in the spreadsheet. CONCLUSIONS: In conclusion, the algorithm provides an automated method for optimization and reduction of PTV margin using logged setup errors from CBCT-based IGRT.

An analytical expression for R50% dependent on PTV surface area and volume: A cranial SRS comparison.

The intermediate dose spill for a stereotactic radiosurgery (SRS) plan can be quantified with the metric R50%, defined as the 50% isodose cloud volume (VIDC50% ) divided by the volume of the planning target volume (PTV). By coupling sound physical principles with the basic definition of R50%, we derive an analytical expression for R50% for a spherical PTV. Our analytical expression depends on three quantities: the surface area of PTV (SAPTV ), the volume of PTV (VPTV ), and the distance of dose drop-off to 50% (Δr). The value of ∆r was obtained from a simple set of cranial phantom plan calculations. We generate values from our analytical expression for R50% (R50%Analytic ) and compare the values to clinical R50% values (R50%Clinical ) extracted from a previously published SRS data set that spans the VPTV range from 0.15 to 50.1 cm3 . R50%Analytic is smaller than R50%Clinical in all cases by an average of 15% ± 7%, and the general trend of R50%Clinical vs VPTV is reflected in the same trend of R50%Analytic . This comparison suggests that R50%Analytic could represent a theoretical lower limit for the clinical SRS data; further investigation is required to confirm this. R50%Analytic could provide useful guidance for what might be achievable in SRS planning.

The surface area effect: How the intermediate dose spill depends on the PTV surface area in SRS.

PURPOSE: Stereotactic radiosurgery (SRS) is rapidly becoming the standard of care for many intracranial targets. The characteristics of the planning target volume (PTV) can affect the intermediate dose spill and thus normal brain volume dose which is correlated with brain toxicity. R50% (volume receiving 50% of prescription dose divided by PTV volume) is a useful metric to quantify the intermediate dose spill. We propose a novel understanding of how the PTV surface area (SAPTV ) affects the intermediate dose spill of SRS treatments. METHODS: Using a phantom model provided by a computed tomography (CT) of the IROC Head Phantom® and Eclipse® Treatment Planning System, we investigate the relationship of R50% and SAPTV in single-target SRS treatments. The planning studies are conducted for SRS treatments on a Varian TrueBeam® linear accelerator with high-definition MLC and a 6 MVFFF beam mode. These data are analyzed to ascertain trends in R50% related to SAPTV . Since SAPTV is not available as a structure property in the Eclipse RTPS, we introduce an Eclipse script to extract PTV surface area of arbitrary-shaped PTVs. We compare a physically reasonable theoretical prediction of R50%, R50%Analytic , to the R50% achieved in treatment planning studies. RESULTS: The SRS phantom study indicates good correlation between the plan R50% and SAPTV . A near-linear relationship of plan R50% vs SAPTV is observed as predicted by the R50%Analytic model. Agreement between plan R50% values and R50%Analytic predictions is good for all but the very smallest PTV volumes. CONCLUSIONS: We demonstrate dependence of the intermediate dose spill measured by R50% on the SAPTV . We call that dependence the surface area effect. This dependence is explicit in the R50%Analytic prediction model. The predicted value of R50%Analytic for a given PTV could be used for guidance during SRS treatment plan optimization, and plan evaluation for that PTV.

Tailoring PTV expansion to improve the dosimetry of post modified radical mastectomy intensity-modulated radiotherapy for left-sided breast cancer patients by using 4D CT combined with cone beam CT.

PURPOSE: Our study aimed to improve the dosimetry of post modified radical mastectomy intensity-modulated radiotherapy (PMRM-IMRT) for left-sided breast cancer patients by tailoring and minimizing PTV expansion three-dimensionally utilizing 4D CT combined with on-board cone beam CT (CBCT). METHODS: We enrolled a total of 10 consecutive left-sided breast cancer patients to undergo PMRM-IMRT. We measured the intra-fractional CTV displacement attributed to respiratory movement by defining 9 points on the left chest wall and quantifying their displacement by using the 4D CT, and measured the inter-fractional CTV displacement resulting from the integrated effect of respiratory movement, thoracic deformation and set up errors by using CBCT. We created 3 different PMRM-IMRT plans for each of the patients using PTVt (tailored PTV expansion three-dimensionally), PTV0.5 and PTV0.7 (isotropic 0.5- cm and isotropic 0.7- cm expanding margin of CTV), respectively. We performed paired samples t test to establish a hierarchy in terms of plan quality and dosimetric benefits. P < 0.05 was considered statistically significant. RESULTS: The inter-fractional CTV displacement (2.6 ± 2.2 mm vertically, 2.8 ± 2.3 mm longitudinally, and 1.7 ± 1.2 mm laterally) measured by CBCT was much larger than the intra-fractional one (0.5 ± 0.5 mm vertically, 0.5 ± 1.0 mm longitudinally, and 0.3 ± 0.3 mm laterally, respectively) measured by 4D CT. Intensity-modulated radiotherapy with tailored PTV expansion based on inter-fractional CTV displacement had dosimetrical advantages over those with PTV0.5 or those with PTV0.7 owing to its perfect PTV dose coverage and better OARs sparing(especially of heart and left lung). CONCLUSION: The CTV displacement in PMRM-IMRT predominantly arises from inter-fraction rather than from intra-fraction during natural respiration and differs in 3 coordinate axes either inter-fractionally or intra-fractionally. Tailoring and minimizing PTV expansion three-dimensionally significantly improves the dosimetry of PMRM-IMRT for left-sided breast cancer patients.

Evaluation of volumetric modulated arc therapy (VMAT) - based total body irradiation (TBI) in pediatric patients.

BACKGROUND: The dosimetric characterization of volumetric modulated arc therapy (VMAT)-based total-body irradiation (TBI) in pediatric patients is evaluated. MATERIALS AND METHODS: Twenty-two patients between the ages of 2 and 12 years were enrolled for VMAT-based TBI from 2018 to 2020. Three isocenters were irradiated over three overlapping arcs. While prescribing 90% of the TBI dose to the planning treatment volume (PTV), two fractions (2 Gy each) were delivered each day; hence 12 Gy was delivered in six fractions. During treatment optimization, the mean lung and kidney doses were set not to exceed 7 Gy and 7.5 Gy, respectively. The maximum lens dose was also set to less than 4 Gy. Patient quality assurance was carried out by comparing treatment planning system doses to the 3-dimensional measured doses by the ArcCHECK® detector. The electronic portal imaging device (EPID) gamma indices were also obtained. RESULTS: The average mean lung dose was 7.75 ± 0.18 Gy, mean kidney dose 7.63 ± 0.26 Gy, maximum lens dose 4.41 ± 0.39 Gy, and the mean PTV dose 12.69 ± 0.16 Gy. The average PTV heterogeneity index was 1.15 ± 0.03. Average differences in mean kidney dose, mean lung dose, and mean target dose were 2.79% ± 0.88, 0.84% ± 0.45 and 0.93% ± 0.47, respectively; when comparing planned and ArcCHECK® measured doses. Only grade 1-2 radiation toxicities were recorded, based on CTCAE v5.0 scoring criteria. CONCLUSIONS: VMAT-TBI was characterized with good PTV coverage, homogeneous dose distribution, planned and measured dose agreement, and low toxicity.

Dosimetric study of Hounsfield number correction effect in areas influenced by contrast product in lungs case.

BACKGROUND: The aim of the study was dosimetric effect quantification of exclusive computed tomography (CT) use with an intravenous (IV) contrast agent (CA ), on dose distribution of 3D-CRT treatment plans for lung cancer. Furthermore, dosimetric advantage investigation of manually contrast-enhanced region overriding, especially the heart. MATERIALS AND METHODS: Ten patients with lung cancer were considered. For each patient two planning CT sets were initially taken with and without CA. Treatment planning were optimized based on CT scans without CA. All plans were copied and recomputed on scans with CA. In addition, scans with IV contrast were copied and density correction was performed for heart contrast enhanced. Same plans were copied and replaced to undo dose calculation errors that may be caused by CA. Eventually, dosimetric evaluations based on dose volume histograms (DVHs) of planning target volumes (PTV) and organs at-risk were studied and analyzed using the Wilcoxon's signed rank test. RESULTS: There is no statistically significant difference in dose calculation for the PTV maximum, mean, minimum doses, spinal cord maximum doses and lung volumes that received 20 and 30 Gy, between planes calculated with and without contrast scans (p > 0.05) and also for contrast scan, with manual regions overriding. CONCLUSIONS: Dose difference caused by the contrast agent is negligible and not significant. Therefore, there is no justification to perform two scans, and using an IV contrast enhanced scan for dose calculation is sufficient.

The effect of designing a rotational planning target volume on sparing pharyngeal constrictor muscles in patients with oropharyngeal cancer.

BACKGROUND: Planning target volume (PTV) has been used to account for variations in tissue, patient and beam position. In oropharyngeal cancers, an isotropic expanded PTV has been used. AIM: The aim of this study was to design a new margin formula that would cover the space occupied by an oropharyngeal clinical target volume (CTV) with ±5-degree rotation around the spine in order to reduce the pharyngeal constrictors overlap with PTV compared to an isotropic expanded PTV. METHODS: We retrospectively evaluated 20 volumetric-modulated arc therapy (VMAT) plans. In order to perform an off-axis rotation, a hypothetical point was placed through the center of the cervical spinal canal and the image was then rotated around the longitudinal axis ±5 degrees. This created a new set of CTVs that were combined to form the new rotational PTV. The overlap between the pharyngeal constrictor muscles (PCMs) and both PTVs was then evaluated. RESULTS: The new rotational PTV causes reduction in the superior PCM overlap in the base of tongue (BOT) lesions compared to tonsillar lesion, 57.8% vs 25.8%, P = 0.01, as well as middle PCM overlap, 73% vs 49%, P = 0.04. Average percent change for PTV volume and overlap with the superior, middle, and inferior PCMs are as followed: -19%, -37%, -59.4%, and -45.2. The smallest isotropic expansion that covers the new rotational PTV was between 3 and 5mm with the average tumor center shift of 0.49 cm. CONCLUSION: This new rotational PTV causes significant reduction of the overlap volume between PCMs and PTVs in order to spare the PCMs compared to isotropic expanded PTV.

Validation of PTV margin for Gamma Knife Icon frameless treatment using a PseudoPatient® Prime anthropomorphic phantom.

The Gamma Knife Icon allows the treatment of brain tumors mask-based single-fraction or fractionated treatment schemes. In clinic, uniform axial expansion of 1 mm around the gross tumor volume (GTV) and a 1.5 mm expansion in the superior and inferior directions are used to generate the planning target volume (PTV). The purpose of the study was to validate this margin scheme with two clinical scenarios: (a) the patient's head remaining right below the high-definition motion management (HDMM) threshold, and (b) frequent treatment interruptions followed by plan adaptation induced by large pitch head motion. A remote-controlled head assembly was used to control the motion of a PseudoPatient® Prime head phantom; for dosimetric evaluations, an ionization chamber, EBT3 films, and polymer gels were used. These measurements were compared with those from the Gamma Knife plan. For the absolute dose measurements using an ionization chamber, the percentage differences for both targets were less than 3.0% for all scenarios, which was within the expected tolerance. For the film measurements, the two-dimensional (2D) gamma index with a 2%/2 mm criterion showed the passing rates of ≥87% in all scenarios except the scenario 1. The results of Gel measurements showed that GTV (D100 ) was covered by the prescription dose and PTV (D95 ) was well above the planned dose by up to 5.6% and the largest geometric PTV offset was 0.8 mm for all scenarios. In conclusion, the current margin scheme with HDMM setting is adequate for a typical patient's intrafractional motion.

A physically meaningful relationship between R50% and PTV surface area in lung SBRT.

PURPOSE: We propose a novel understanding of two characteristics of the planning target volume (PTV) that affect the intermediate-dose spill in lung stereotactic body radiation therapy (SBRT) as measured by R50%. This phantom model research investigates two characteristics of the PTV that have a marked effect on the value of R50%: the mean dose deposited within the PTV (Dav ) and the surface area of the PTV (SAPTV ). METHODS: Using a phantom model provided by a CT of the IROC Thorax-Lung Phantom® (IROC Houston QA Center, Houston, TX) and Eclipse® Treatment Planning System (Varian Medical Systems, Palo Alto, CA), we investigate the two characteristics for spherical and cylindrical PTVs. A total of 135 plans with tightly controlled PTV characteristics are employed. A lower bound for R50% (R50%min∆r ) is derived and clearly establishes a relationship between R50% and SAPTV that has not been fully appreciated previously. RESULTS: The study of PTV Dav revealed a local minimum for R50% as a function of the PTV Dav at Dav  ≈ 110% of Rx dose. As PTV Dav increases above this local minimum, R50% increases; while for PTV Dav less than this local minimum, the R50% value also increases. The study of PTV surface area (SAPTV ) demonstrated that as the SAPTV increases, the R50% increases if the PTV volume stays the same. The SAPTV result is predicted by the theoretical investigation that yields the R50% lower bound, R50%min∆r . CONCLUSIONS: This research has identified two characteristics of the PTV that have a marked influence on R50%: PTV Dav and SAPTV . These characteristics have not been clearly articulated in the vast body of previous research in SBRT. These results could help explain plans that cannot meet the RTOG criteria for R50%. With further development, these concepts could be extended to provide additional guidance for creating acceptable SBRT plans.

An analytical expression for R50% dependent on PTV surface area and volume: a lung SBRT comparison.

In stereotactic body radiation therapy (SBRT), R50% is a common metric for intermediate dose spill and is defined in RTOG 0915 as the ratio of 50% isodose cloud volume (IDC50%) to the planning target volume (PTV). By coupling sound physical principles with the basic definition of intermediate dose spill, we derive an exact analytical expression for R50% for the case of a spherical volume. This expression for R50% depends on three quantities: the surface area of PTV (SAPTV ), the volume of PTV (VPTV ), and the dose gradient Δr. Validity of our analytical expression for R50% was confirmed via direct comparison to peer-reviewed, multi-institutional, diverse clinical data. The comparison of our R50% values computed from our analytical expression to the clinical data yielded an average percent difference of 3.8 ± 4.5%.

Observer uncertainties of soft tissue-based patient positioning in IGRT.

PURPOSE: There remain uncertainties due to inter- and intraobserver variability in soft-tissue-based patient positioning even with the use of image-guided radiation therapy (IGRT). This study aimed to reveal observer uncertainties of soft-tissue-based patient positioning on cone-beam computed tomography (CBCT) images for prostate cancer IGRT. METHODS: Twenty-six patients (7-8 fractions/patient, total number of 204 fractions) who underwent IGRT for prostate cancer were selected. Six radiation therapists retrospectively measured prostate cancer location errors (PCLEs) of soft-tissue-based patient positioning between planning CT (pCT) and pretreatment CBCT (pre-CBCT) images after automatic bone-based registration. Observer uncertainties were evaluated based on residual errors, which denoted the differences between soft-tissue and reference positioning errors. Reference positioning errors were obtained as PCLEs of contour-based patient positioning between pCT and pre-CBCT images. Intraobserver variations were obtained from the difference between the first and second soft-tissue-based patient positioning repeated by the same observer for each fraction. Systematic and random errors of inter- and intraobserver variations were calculated in anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions. Finally, clinical target volume (CTV)-to-planning target volume (PTV) margins were obtained from systematic and random errors of inter- and intraobserver variations in AP, SI, and LR directions. RESULTS: Interobserver variations in AP, SI, and LR directions were 0.9, 0.9, and 0.5 mm, respectively, for the systematic error, and 1.8, 2.2, and 1.1 mm, respectively, for random error. Intraobserver variations were <0.2 mm in all directions. CTV-to-PTV margins in AP, SI, and LR directions were 3.5, 3.8, and 2.1 mm, respectively. CONCLUSION: Intraobserver variability was sufficiently small and would be negligible. However, uncertainties due to interobserver variability for soft-tissue-based patient positioning using CBCT images should be considered in CTV-to-PTV margins.

Dosimetric impact on changes in target volumes during intensity-modulated radiotherapy for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact. PATIENTS AND METHODS: Twenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated. RESULTS: We observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01). CONCLUSION: Tumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients.

Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques.

AIM: Our goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas. BACKGROUND: RT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR). MATERIALS AND METHODS: We conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI). RESULTS: Fifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF. CONCLUSIONS: Our results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.

Pelvic radiation therapy with volumetric modulated arc therapy and intensity-modulated radiotherapy after renal transplant: A report of 3 cases.

AIM: Describe characteristics and outcomes of three patients treated with pelvic radiation therapy after kidney transplant. BACKGROUND: The incidence of pelvic cancers in kidney transplant (KT) recipients is rising. Currently it is the leading cause of death. Moreover, treatment is challenging because anatomical variants, comorbidities, and associated treatments, which raises the concern of using radiotherapy (RT). RT has been discouraged due to the increased risk of urethral/ureteral stricture and KT dysfunction. MATERIALS AND METHODS: We reviewed the electronic health records and digital planning system of patients treated with pelvic RT between December 2013 and December 2018 to identify patients with previous KT. CASES DESCRIPTION: We describe three successful cases of KT patients in which modern techniques allowed full standard RT for pelvic malignances (2 prostate and 1 vaginal cancer) with or without elective pelvic nodal RT, without allograft toxicity at short and long follow-up (up to 60 months). CONCLUSION: When needed, RT modern techniques remain a valid option with excellent oncologic results and acceptable toxicity. Physicians should give special considerations to accomplish all OAR dose constraints in the patient's specific setting. Recent publications recommend KT mean dose <4 Gy, but graft proximity to CTV makes this unfeasible. We present 2 cases where dose constraint was not achieved, and to a short follow-up of 20 months renal toxicity has not been documented. We recommend the lowest possible mean dose to the KT, but never compromising the CTV coverage, since morbimortality from recurrent or progressive cancer disease outweighs the risk of graft injury.