Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC.

BACKGROUND: Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses; therefore, we evaluated the efficacy and safety of sotorasib 960 mg and 240 mg. METHODS: In this phase 2, randomized, open-label study, adults with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg or 240 mg once daily. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetics. The study was not powered for formal statistical hypothesis testing. RESULTS: In the 960 mg group (n = 104), ORR was 32.7 % and DCR was 86.5 %. In the 240 mg group (n = 105), ORR was 24.8 % and DCR was 81.9 %. Median PFS was 5.4 months (960 mg) and 5.6 months (240 mg). At a median follow-up of 17.5 months, median OS was 13.0 months (960 mg) and 11.7 months (240 mg). AUC0-24 h and Cmax were 1.3-fold numerically higher with the 960 mg dose. Treatment-emergent adverse events (TEAEs, ≥10 %) for 960 mg and 240 mg doses, respectively, were diarrhea (39.4 %; 31.7 %), nausea (23.1 %; 19.2 %), increased alanine aminotransaminase (14.4 %; 17.3 %), and increased aspartate aminotransferase (13.5 %; 13.5 %). CONCLUSIONS: Patients treated with sotorasib 960 mg once daily had numerically higher ORR and DCR, and longer DOR and OS, than patients treated with 240 mg in this descriptive analysis. TEAEs were manageable with label-directed dose modifications. CLINICAL TRIAL REGISTRATION: NCT03600883.

Dosimetric Comparison Study Between Free Breathing and Breath Hold Techniques in Patients Treated by Liver-Directed Stereotactic Body Radiation Therapy.

Background Breathing motion management is the key to delivering stereotactic body radiation therapy (SBRT) for liver lesions. This study aimed to compare the dosimetric parameters of liver SBRT using two different techniques: free breathing and breath hold. Method The study included 11 patients with liver metastases or hepatocellular carcinoma who underwent liver-directed SBRT. A dosimetric comparison was performed using dose-volume histogram analysis, evaluating parameters such as the maximum dose to 5 cc of bowel volume, mean liver dose (MLD), and liver V20 and V30. Statistical analyses were performed to compare results. Results The findings revealed that the breath hold technique resulted in significantly lower doses to the bowel and smaller volumes of normal liver tissue receiving 20 Gy (V20) and 30 Gy (V30) than the free breathing. Although there was no statistically significant difference in the MLD between the two techniques, the breath hold technique resulted in a lower MLD. Conclusion This dosimetric comparison study suggests that the breath hold technique is associated with lower radiation exposure to the bowel and normal liver tissues. Although this may not be feasible for all patients, it may be an appropriate procedure for selected individuals. Further research is needed to validate these findings in different patient populations and explore their impact on clinical outcomes and patient-reported quality of life.

Weight-bearing gantry-free cone-beam CT of the lumbar spine: Image quality analysis and dose efficiency.

PURPOSE: The effect of static forces under load limits the prognostic value of lumbar spine CT in a horizontal position. Using a gantry-free scanner architecture, this study was designed to assess the feasibility of weight-bearing cone-beam CT (CBCT) of the lumbar spine and to establish the most dose-effective combination of scan parameters. METHODS: Eight formalin-fixated cadaveric specimens were examined with a gantry-free CBCT system in upright position with the aid of a dedicated positioning backstop. Cadavers were scanned with eight combinations of tube voltage (102 or 117 kV), detector entrance dose level (high or low), and frame rates (16 or 30 fps). Five radiologists independently analyzed datasets for overall image quality and posterior wall assessability. Additionally, image noise and signal-to-noise ratio (SNR) were compared based on region-of-interest (ROI) measurements in the gluteal muscles. RESULTS: Radiation dose ranged from 6.8 ± 1.6 (117 kV, dose level low, 16 fps) to 24.3 ± 6.3 mGy (102 kV, dose level high, 30 fps). Both image quality and posterior wall assessability were favored with 30 over 16 fps (all p ≤ 0.008). In contrast, both tube voltage (all p > 0.999) and dose level (all p > 0.096) did not significantly impact reader assessment. Image noise decreased considerably with higher frame rates (all p ≤ 0.040), while SNR ranged from 0.56 ± 0.03 to 1.11 ± 0.30 without a significant difference between scan protocols (all p ≥ 0.060). CONCLUSIONS: Employing an optimized scan protocol, weight-bearing gantry-free CBCT of the lumbar spine allows for diagnostic imaging at reasonable radiation dose.

Helical tomotherapy and two types of volumetric modulated arc therapy: dosimetric and clinical comparison for several cancer sites.

Radiotherapy accelerators have undergone continuous technological developments. We investigated the differences between Radixact™ and VMAT treatment plans. Sixty patients were included in this study. Dosimetric comparison between the Radixact™ and VMAT plans was performed for six cancer sites: whole-brain, head and neck, lymphoma, lung, prostate, and rectum. The VMAT plans were generated with two Elekta linear accelerators (Synergy® and Versa HD™). The planning target volume (PTV) coverage, organs-at-risk dose constraints, and four dosimetric indexes were considered. The deliverability of the plans was assessed using quality assurance (gamma index evaluation) measurements; clinical judgment was included in the assessment. The mean AAPM TG218 (3%-2 mm, global normalization) gamma index values were 99.4%, 97.8%, and 96.6% for Radixact™, Versa HD™, and Synergy®, respectively. Radixact™ performed better than Versa HD™ in terms of dosimetric indexes, hippocampi D100%, spinal cord Dmax, rectum V38.4  Gy, bladder V30 Gy, and V40 Gy. Versa HD™ saved more of the (lungs-PTV) V5 Gy and (lungs-PTV) Dmean, heart Dmean, breasts V4 Gy, and bowel V45 Gy. Regarding Synergy®, the head and neck Radixact™ plan saved more of the parotid gland, oral cavity, and supraglottic larynx. From a clinical point of view, for the head and neck, prostate, and rectal sites, the Radixact™ and Versa HD™ plans were similar; Radixact™ plans were preferable for the head and neck and rectum to Synergy® plans. The quality of linac plans has improved, and differences with tomotherapy have decreased. However, tomotherapy continues to be an essential add-on in multi-machine departments.

Automated Non-coplanar Volumetric Modulated Arc Therapy Planning for Maxillary Sinus Carcinoma.

BACKGROUND/AIM: Dosimetric parameters in volumetric modulated arc therapy (VMAT), non-coplanar VMAT (NC-VMAT), and automated NC-VMAT (HyperArc, HA) were compared for patients with maxillary sinus carcinoma (MSC). PATIENTS AND METHODS: Twenty HA plans were generated to deliver 70.4, 64, and 46 Gy for planning target volumes with high (PTV1), intermediate (PTV2), and low risk (PTV3), respectively. The VMAT and NC-VMAT plans were retrospectively generated using the same optimized parameters as those used in the HA plans. RESULTS: For PTV1, the three treatment plans provided comparable target coverages. For PTV2, the D95%, D99%, and Dmin in the HA plans (64.7±1.2, 62.7±2.1 and 54.6±6.2 Gy, respectively) were significantly higher (p<0.05) than those in the VMAT plans (64.3±1.7, 61.9±2.4 and 52.9±6.4 Gy, respectively). The NC-VMAT and HA plans provided significantly higher (p<0.05) dosimetric parameters for PTV3 than those in the VMAT plans, and D99% in the HA was significantly higher than that in the NC-VMAT plans (52.5±3.0 vs. 51.8±2.7 Gy, p<0.05). The doses to the brain and brainstem were lowest in the HA plans (p<0.05). Moreover, dosimetric parameters of the contralateral organs (lens, optic nerve, retina, and parotid) were lower in the HA plans than in the VMAT and NC-VMAT plans. CONCLUSION: The HA plans provided the best target coverage and OAR sparing compared with VMAT and NC-VMAT plans for patients with MSC.

The influence of beam optics asymmetric distribution on dose in scanning carbon-ion radiotherapy.

PURPOSE: To quantify the influence of beam optics asymmetric distribution on dose. METHODS: Nine reference cubic targets and corresponding plans with modulation widths (M) of 3, 6, and 9 cm and with center depths (CDs) of 6, 12, and 24 cm were generated by the treatment planning system (TPS). The Monte Carlo code FLUKA was used for simulating the dose distribution from the aforementioned original plans and the dose perturbation by varying ±5%, ±15%, ±20%, ±25%, and ±40% in spot full width half maximum to the X-direction while keeping consistent in the Y-direction. The dosimetric comparisons in dose deviation, γ-index analysis, lateral penumbra, and flatness were evaluated. RESULTS: The largest 3D absolute mean deviation was 15.0% ± 20.9% (mean ± standard deviation) in M3CD6, whereas with the variation from -15% to +20%, the values were below 5% for all cube plans. The lowest 2D γ-index passing rate was 80.6% with criteria of 2%-2 mm by a +40% variation in M3CD6. For the M9CD24 with a -40% variation, the maximum 1D dose deviations were 5.6% and 15.7% in the high-dose region and the edge of the radiation field, respectively. The maximum deviations of penumbra and flatness were 3.4 mm and 11.4%, respectively. CONCLUSIONS: The scenario of beam optics asymmetric showed relatively slight influence on the global dose distribution but severely affected dose on the edge of the radiation field. For scanning carbon-ion therapy facilities, beam spot lateral profile settings in TPS base data should be properly handled when beam optics asymmetry variation is over 15%.

Model refinement increases confidence levels and clinical agreement when commissioning a three-dimensional secondary dose calculation system.

PURPOSE: Evaluate custom beam models for a second check dose calculation system using statistically verifiable passing criteria for film analysis, DVH, and 3D gamma metrics. METHODS: Custom beam models for nine linear accelerators for the Sun Nuclear Dose Calculator algorithm (SDC, Sun Nuclear) were evaluated using the AAPM-TG119 test suite (5 Intensity Modulated Radiation Therapy (IMRT) and 5 Volumetric Modulated Arc Therapy (VMAT) plans) and a set of clinical plans. Where deemed necessary, adjustments to Multileaf Collimator (MLC) parameters were made to improve results. Comparisons to the Analytic Anisotropic Algorithm (AAA), and gafchromic film measurements were performed. Confidence intervals were set to 95% per TG-119. Film gamma criteria were 3%/3 mm (conventional beams) or 3%/1 mm (Stereotactic Radiosurgery [SRS] beams). Dose distributions in solid water phantom were evaluated based on DVH metrics (e.g., D95, V20) and 3D gamma criteria (3%/3 mm or 3%/1 mm). Film passing rates, 3D gamma passing rates, and DVH metrics were reported for HD MLC machines and Millennium MLC Machines. RESULTS: For HD MLC machines, SDC gamma film agreement was 98.76% ± 2.30% (5.74% CL) for 6FFF/6srs (3%/1 mm), and 99.80% ± 0.32% (0.83% CL) for 6x (3%/3 mm). For Millennium MLC machines, film passing rates were 98.20% ± 3.14% (7.96% CL), 99.52% ± 1.14% (2.71% CL), and 99.69% ± 0.82% (1.91% CL) for 6FFF, 6x, and 10x, respectively. For SDC to AAA comparisons: HD MLC Linear Accelerators (LINACs); DVH point agreement was 0.97% ± 1.64% (4.18% CL) and 1.05% ± 2.12% (5.20% CL); 3D gamma agreement was 99.97% ± 0.14% (0.30% CL) and 100.00% ± 0.02% (0.05% CL), for 6FFF/6srs and 6x, respectively; Millennium MLC LINACs: DVH point agreement was 0.77% ± 2.40% (5.47% CL), 0.80% ± 3.40% (7.47% CL), and 0.07% ± 2.15% (4.30% CL); 3D gamma agreement was 99.97% ± 0.13% (0.29% CL), 99.97% ± 0.17% (0.36% CL), and 99.99% ± 0.06% (0.12% CL) for 6FFF, 6x, and 10x, respectively. CONCLUSION: SDC shows agreement well within TG119 CLs for film and redundant dose calculation comparisons with AAA. In some models (SRS), this was achieved using stricter criteria. TG119 plans can be used to help guide model adjustments and to establish clinical baselines for DVH and 3D gamma criteria.

Methylprednisolone Treatment in Brain Death-Induced Lung Inflammation-A Dose Comparative Study in Rats.

Background: The process of brain death (BD) leads to a pro-inflammatory state of the donor lung, which deteriorates its quality. In an attempt to preserve lung quality, methylprednisolone is widely recommended in donor lung management. However, clinical treatment doses vary and the dose-effect relation of methylprednisolone on BD-induced lung inflammation remains unknown. The aim of this study was to investigate the effect of three different doses methylprednisolone on the BD-induced inflammatory response. Methods: BD was induced in rats by inflation of a Fogarty balloon catheter in the epidural space. After 60 min of BD, saline or methylprednisolone (low dose (5 mg/kg), intermediate dose (12.5 mg/kg) or high dose (22.5 mg/kg)) was administered intravenously. The lungs were procured and processed after 4 h of BD. Inflammatory gene expressions were analyzed by RT-qPCR and influx of neutrophils and macrophages were quantified with immunohistochemical staining. Results: Methylprednisolone treatment reduced neutrophil chemotaxis as demonstrated by lower IL-8-like CINC-1 and E-selectin levels, which was most evident in rats treated with intermediate and high doses methylprednisolone. Macrophage chemotaxis was attenuated in all methylprednisolone treated rats, as corroborated by lower MCP-1 levels compared to saline treated rats. Thereby, all doses methylprednisolone reduced TNF-α, IL-6 and IL-1ß tissue levels. In addition, intermediate and high doses methylprednisolone induced a protective anti-inflammatory response, as reflected by upregulated IL-10 expression when compared to saline treated brain-dead rats. Conclusion: We showed that intermediate and high doses methylprednisolone share most potential to target BD-induced lung inflammation in rats. Considering possible side effects of high doses methylprednisolone, we conclude from this study that an intermediate dose of 12.5 mg/kg methylprednisolone is the optimal treatment dose for BD-induced lung inflammation in rats, which reduces the pro-inflammatory state and additionally promotes a protective, anti-inflammatory response.

Low-Dose CT in Pelvic Imaging: Comparing Dose and Image Quality in Relation to Clinical Value in a Phantom Study.

OBJECTIVE. The aim of this phantom study was to determine whether low-dose CT of the pelvis can be performed using a dose similar to that used in a standard radio-graphic examination and to ascertain whether CT, with its better delineation of complex structures, has greater clinical value than radiography and therefore will result in improved patient care. Special consideration was given to CT performed using the tin filtration technique. MATERIALS AND METHODS. For dose comparison, an anthropomorphic phantom with 20 thermoluminescent dosimeters, two different CT scanners, and three conventional radiography devices were used. Seven CT protocols (including tin filtration) and four different radiographic examinations were performed. Dose calculations, objective and subjective evaluations of image quality, and figure-of-merit calculations were compared among the techniques. Furthermore, the images obtained were evaluated in a clinical context. Intraclass correlation was determined for the subjective results. RESULTS. The dose values of the tested low-dose CT protocols, in particular those using the tin filtration technique, corresponded to or were only slightly higher than the dose values of conventional pelvic radiographic images obtained in three views. Low-dose CT examinations were rated sufficient for consolidation control and had an informative value that was significantly higher than that of conventional radiography. Tin filtering showed the best results for low-dose CT in terms of combining dose and clinically relevant image quality. CONCLUSION. In this phantom study, low-dose CT was superior to radiography for visualizing and evaluating the dorsal pelvic ring, with only marginally higher radiation exposure occurring when the latest-generation CT systems were used. Tin filtration can improve image quality, create further dose reductions, or provide both benefits.

Quantitative comparison of pre-treatment predictive and post-treatment measured dosimetry for selective internal radiation therapy using cone-beam CT for tumor and liver perfusion territory definition.

BACKGROUND: Selective internal radiation therapy (SIRT) is a promising treatment for unresectable hepatic malignancies. Predictive dose calculation based on a simulation using 99mTc-labeled macro-aggregated albumin (99mTc-MAA) before the treatment is considered as a potential tool for patient-specific treatment planning. Post-treatment dose measurement is mainly performed to confirm the planned absorbed dose to the tumor and non-tumor liver volumes. This study compared the predicted and measured absorbed dose distributions. METHODS: Thirty-one patients (67 tumors) treated by SIRT with resin microspheres were analyzed. Predicted and delivered absorbed dose was calculated using 99mTc-MAA-SPECT and 90Y-TOF-PET imaging. The voxel-level dose distribution was derived using the local deposition model. Liver perfusion territories and tumors have been delineated on contrast-enhanced CBCT images, which have been acquired during the 99mTc-MAA work-up. Several dose-volume histogram (DVH) parameters together with the mean dose for liver perfusion territories and non-tumoral and tumoral compartments were evaluated. RESULTS: A strong correlation between the predicted and measured mean dose for non-tumoral volume was observed (r = 0.937). The ratio of measured and predicted mean dose to this volume has a first, second, and third interquartile range of 0.83, 1.05, and 1.25. The difference between the measured and predicted mean dose did not exceed 11 Gy. The correlation between predicted and measured mean dose to the tumor was moderate (r = 0.623) with a mean difference of - 9.3 Gy. The ratio of measured and predicted tumor mean dose had a median of 1.01 with the first and third interquartile ranges of 0.58 and 1.59, respectively. Our results suggest that 99mTc-MAA-based dosimetry could predict under or over dosing of the non-tumoral liver parenchyma for almost all cases. For more than two thirds of the tumors, a predictive absorbed dose correctly indicated either good tumor dose coverage or under-dosing of the tumor. CONCLUSION: Our results highlight the predictive value of 99mTc-MAA-based dose estimation to predict non-tumor liver irradiation, which can be applied to prescribe an optimized activity aiming at avoiding liver toxicity. Compared to non-tumoral tissue, a poorer agreement between predicted and measured absorbed dose is observed for tumors.

Modeling Pathway Dynamics of the Skeletal Muscle Response to Intravenous Methylprednisolone (MPL) Administration in Rats: Dosing and Tissue Effects.

A model-based approach for the assessment of pathway dynamics is explored to characterize metabolic and signaling pathway activity changes characteristic of the dosing-dependent differences in response to methylprednisolone in muscle. To consistently compare dosing-induced changes we extend the principles of pharmacokinetics and pharmacodynamics and introduce a novel representation of pathway-level dynamic models of activity regulation. We hypothesize the emergence of dosing-dependent regulatory interactions is critical to understanding the mechanistic implications of MPL dosing in muscle. Our results indicate that key pathways, including amino acid and lipid metabolism, signal transduction, endocrine regulation, regulation of cellular functions including growth, death, motility, transport, protein degradation, and catabolism are dependent on dosing, exhibiting diverse dynamics depending on whether the drug is administered acutely of continuously. Therefore, the dynamics of drug presentation offer the possibility for the emergence of dosing-dependent models of regulation. Finally, we compared acute and chronic MPL response in muscle with liver. The comparison revealed systematic response differences between the two tissues, notably that muscle appears more prone to adapt to MPL.

Dose Calculation Comparisons between Three Modern Treatment Planning Systems.

PURPOSE: Monaco treatment planning system (TPS) version 5.1 uses a Monte-Carlo (MC)-based dose calculation engine. The aim of this study is to verify and compare the Monaco-based dose calculations with both Pinnacle3 collapsed cone convolution superposition (CCCS) and Eclipse anisotropic analytical algorithm (AAA) calculations. MATERIALS AND METHODS: For this study, 18 previously treated lung and head-and-neck (HN) cancer patients were chosen to compare the dose calculations between Pinnacle, Monaco, and Eclipse. Plans were chosen from those that had been treated using the Elekta VersaHD or a Novalis Tx linac. All of the treated volumetric-modulated arc therapy plans used 6 MV or 10 MV photon beams. The original plans calculated with CCCS or AAA along with the recalculated ones using MC from the three TPS were exported into Velocity software for intercomparison. RESULTS: To compare the dose calculations, Planning target volume (PTV) heterogeneity indexes and conformity indexes were calculated from the dose volume histograms (DVH) of all plans. While mean lung dose (MLD), lung V5 and V20 values were recorded for lung plans, the computed dose to parotids, brainstem, and mandible were documented for HN plans. In plan evaluation, percent differences of the above dosimetric values in Monaco computation were compared against each of the other TPS computations. CONCLUSION: It could be concluded through this research that there can be differences in the calculation of dose across different TPSs. Although relatively small, these differences could become apparent when compared using DVH. These differences most likely arise from the different dose calculation algorithms used in each TPS. Monaco employs the MC allowing it to have much more detailed calculations that result in it being seen as the most accurate and the gold standard.

Clinical utility, dose determination, and safety of ocular contrast-enhanced ultrasonography in horses: A pilot study.

OBJECTIVE: To determine efficacy of contrast-enhanced ultrasonography (CEUS) using different sulfur hexafluoride (SF6) doses to assess blood flow and perfusion in equine eyes and to evaluate safety of SF6 in horses. PROCEDURES: Ocular B-mode and contrast-enhanced ultrasonography were performed bilaterally in nine sedated university-owned horses. Intravenous SonoVue® bolus injections of 5, 10, 15, 20, 25, and 30 mL were administered for 2/18, 5/18, 6/18, 3/18, 1/18, and 1/18 eyes, respectively. Doses were increased based on ascending bodyweight. Each eye within one horse was examined utilizing a different dose. Qualitative blood flow and quantitative perfusion were analyzed. Heart and respiratory rates were monitored nonsedated, sedated, and during first and second minutes of CEUS. RESULTS: Qualitative contrast enhancement (CE) was visible in 7/9 animals. Quantitative CE was measurable bilaterally in four horses, unilaterally in three individuals, and not detected in two animals. In all horses with unilateral CE, the positive eye received the higher dose. Fifteen mL dose resulted in significantly shorter time to peak than 10 mL (P < .05). Peak intensity, maximum signal increase, and corresponding area under the curve were significantly higher for 15 and 20 mL doses compared with 10 mL (P < .05). Uveal and retinal tissues were enhanced frequently. Twenty-five and 30 mL doses revealed no CE. Only sedation reduced heart rates significantly (P < .05). Clinically relevant changes in respiratory rates or adverse reactions following SF6 application were not observed. CONCLUSIONS: Contrast enhancement was in most instances dose-dependent. Fifteen mL appeared appropriate to assess equine ocular perfusion. The reliability in horses remains questionable; however, CEUS was well-tolerated.

Study on the effects of different CT values assignment methods on dose calculation of brain metastases radiotherapy / 中华放射医学与防护杂志

Objective@#To study the effects of different CT values assignment methods on the dose calculation of radiotherapy plan for brain metastases, which will provide a reference for radiotherapy treatment planning based on MR images.@*Methods@#A total of 35 patients treated with radiotherapy for brain metastases were selected, with pre-treatment CT and MR simulated positioning performed at the same day. Based on the simulation CT images, three dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) plans were calculated as the original plan (Plan1). The CT and MR images were rigidly registered and then the main tissues and organs were delineated on CT and MR images. The average CT values of each tissue and organ were calculated. Three groups of pseudo CT were generated by three CT values assignment methods based on the CT images: whole tissue was assigned 140 HU; cavity, bone and other tissues were assigned -700 HU, 700 HU and 20 HU, respectively; different tissues and organs were assigned corresponding CT values. The dose distribution of Plan1 was recalculated on three groups of pseudo-CT to obtain Plan2, Plan3 and Plan4, respectively. Finally, the dosimetric difference between Plan1 and other plans (including Plan2, Plan3 and Plan4) were compared.@*Results@#The average CT values of bone and cavity were (735.3±68.0) HU and (-723.9±27.0) HU, respectively. The average CT values of soft tissues was mostly distributed from -70 to 70 HU. The dosimetric differences between Plan2, Plan3, Plan4, and Plan1 decreased in turn. The differences of maximum dose of lens were the biggest, which can reach more than 5.0%, 1.5%-2.0% and 1.0%-1.5%, respectively, and the differences of other dose parameters were basically less than 2.0%, 1.2% and 0.8%, respectively. In the pixelwise dosimetric comparison, the areas with more than 1% difference in the local target cases were mainly distributed in the skin near the field. On the other hand, those in the whole brain target cases were mainly distributed at the bone, cavity, bone and soft tissues junction, and the skin near the field. In addition, the dose calculation error of CT value assignment methods in 3D-CRT plan was slightly larger than that in IMRT plan, and that in whole brain target cases were significantly larger than that in local target cases.@*Conclusions@#Different CT value assignment methods have a significant effect on the dose calculation of radiotherapy for brain metastases. When appropriate CT values are given to bone, air cavity and soft tissue, respectively, the deviation of dose calculation can be basically controlled within 1.2%. And by assigning mass CT values to various tissues and organs, the deviation can be further controlled within 0.8%, which can meet the clinical requirements.

Study on the effects of different CT values assignment methods on dose calculation of brain metastases radiotherapy / 中华放射医学与防护杂志

Objective To study the effects of different CT values assignment methods on the dose calculation of radiotherapy plan for brain metastases,which will provide a reference for radiotherapy treatment planning based on MR images.Methods A total of 35 patients treated with radiotherapy for brain metastases were selected,with pre-treatment CT and MR simulated positioning performed at the same day.Based on the simulation CT images,three dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) plans were calculated as the original plan (Plan1).The CT and MR images were rigidly registered and then the main tissues and organs were delineated on CT and MR images.The average CT values of each tissue and organ were calculated.Three groups of pseudo CT were generated by three CT values assignment methods based on the CT images:whole tissue was assigned 140 HU;cavity,bone and other tissues were assigned-700 HU,700 HU and 20 HU,respectively;different tissues and organs were assigned corresponding CT values.The dose distribution of Plan1 was recalculated on three groups of pseudo-CT to obtain Plan2,Plan3 and Plan4,respectively.Finally,the dosimetric difference between Plan1 and other plans (including Plan2,Plan3 and Plan4) were compared.Results The average CT values of bone and cavity were (735.3 ± 68.0) HU and (-723.9 ± 27.0) HU,respectively.The average CT values of soft tissues was mostly distributed from-70 to 70 HU.The dosimetric differences between Plan2,Plan3,Plan4,and Plan1 decreased in turn.The differences of maximum dose of lens were the biggest,which can reach more than 5.0％,1.5％-2.0％ and 1.0％-1.5％,respectively,and the differences of other dose parameters were basically less than 2.0％,1.2％and 0.8％,respectively.In the pixelwise dosimetric comparison,the areas with more than 1％ difference in the local target cases were mainly distributed in the skin near the field.On the other hand,those in the whole brain target cases were mainly distributed at the bone,cavity,bone and soft tissues junction,and the skin near the field.In addition,the dose calculation error of CT value assignment methods in 3D-CRT plan was slightly larger than that in IMRT plan,and that in whole brain target cases were significantly larger than that in local target cases.Conclusions Different CT value assignment methods have a significant effect on the dose calculation of radiotherapy for brain metastases.When appropriate CT values are given to bone,air cavity and soft tissue,respectively,the deviation of dose calculation can be basically controlled within 1.2％.And by assigning mass CT values to various tissues and organs,the deviation can be further controlled within 0.8％,which can meet the clinical requirements.

Analysis of dose comparison techniques for patient-specific quality assurance in radiation therapy.

PURPOSE: Gamma evaluation is the most commonly used technique for comparison of dose distributions for patient-specific pretreatment quality assurance in radiation therapy. Alternative dose comparison techniques have been developed but not widely implemented. This study aimed to compare and evaluate the performance of several previously published alternatives to the gamma evaluation technique, by systematically evaluating a large number of patient-specific quality assurance results. METHODS: The agreement indices (or pass rates) for global and local gamma evaluation, maximum allowed dose difference (MADD) and divide and conquer (D&C) techniques were calculated using a selection of acceptance criteria for 429 patient-specific pretreatment quality assurance measurements. Regression analysis was used to quantify the similarity of behavior of each technique, to determine whether possible variations in sensitivity might be present. RESULTS: The results demonstrated that the behavior of D&C gamma analysis and MADD box analysis differs from any other dose comparison techniques, whereas MADD gamma analysis exhibits similar performance to the standard global gamma analysis. Local gamma analysis had the least variation in behavior with criteria selection. Agreement indices calculated for 2%/2 mm and 2%/3 mm, and 3%/2 mm and 3%/3 mm were correlated for most comparison techniques. CONCLUSION: Radiation oncology treatment centers looking to compare between different dose comparison techniques, criteria or lower dose thresholds may apply the results of this study to estimate the expected change in calculated agreement indices and possible variation in sensitivity to delivery dose errors.

Radiation exposure related to cardiovascular CT examination: comparison between conventional 64-MDCT and third-generation dual-source MDCT.

PURPOSE: To compare radiation exposure associated with daily practice cardiovascular (CV) examinations performed on two different multidetector computed tomography (MDCT) scanners, a conventional 64-MDCT and a third-generation dual-source (DS) MDCT. MATERIALS AND METHODS: In this retrospective study, 1458 patients who underwent CV examinations between January 2017 and August 2018 were enrolled. A single-source 64-MDCT (Lightspeed VCT, GE) scan was performed in 705 patients from January to August 2017 (207 coronary examinations and 498 vascular examinations) and 753 patients underwent third-generation 192 × 2-DSCT (Somatom FORCE, Siemens) scan from January to August 2018 (302 coronary examinations and 451 vascular examinations). Volume CT dose index (CTDIvol), dose length product (DLP), effective dose (ED), tube voltage (TV) and exposure time (ET), pitch factor (PF) were registered for each patient. Student's t test was used to compare mean values between each corresponding group of MDCT and DSCT. RESULTS: In coronary examinations with DSCT, CTDIvol was 24.4% lower (23.1 mGy vs 30.6 mGy, p < 0.0001) and DLP and ED reductions were 35.6% than with MDCT (465.0 mGy * cm vs 732.3 mGy * cm and 6.5 mSv and 10.3 mSv; vs p < 0.0001). Concerning scan parameters, kVp and ET reductions were 12.7% and 69.4%, respectively (p < 0.0001); PF increase was 73.8% (p < 0.0001). In all vascular studies, DSCT, compared with MDCT, permitted to reduce CTDIvol from 43.5 to 70.6%; DLP and ED reductions were from 50.3 to 73.1%; kVp and ET decreases were from 10.7 to 32.5% and from 26.3 to 68.7%. PF increase was from 16.7 to 58.1% (all differences with p < 0.0001). CONCLUSIONS: In daily practice, CV examinations CTDI, DLP, ED, ET and TV were lower and PF was higher with 192 × 2-DSCT compared to 64-MDCT.

Pathway-Based Analysis of the Liver Response to Intravenous Methylprednisolone Administration in Rats: Acute Versus Chronic Dosing.

Pharmacological time-series data, from comparative dosing studies, are critical to characterizing drug effects. Reconciling the data from multiple studies is inevitably difficult; multiple in vivo high-throughput -omics studies are necessary to capture the global and temporal effects of the drug, but these experiments, though analogous, differ in (microarray or other) platforms, time-scales, and dosing regimens and thus cannot be directly combined or compared. This investigation addresses this reconciliation issue with a meta-analysis technique aimed at assessing the intrinsic activity at the pathway level. The purpose of this is to characterize the dosing effects of methylprednisolone (MPL), a widely used anti-inflammatory and immunosuppressive corticosteroid (CS), within the liver. A multivariate decomposition approach is applied to analyze acute and chronic MPL dosing in male adrenalectomized rats and characterize the dosing-dependent differences in the dynamic response of MPL-responsive signaling and metabolic pathways. We demonstrate how to deconstruct signaling and metabolic pathways into their constituent pathway activities, activities which are scored for intrinsic pathway activity. Dosing-induced changes in the dynamics of pathway activities are compared using a model-based assessment of pathway dynamics, extending the principles of pharmacokinetics/pharmacodynamics (PKPD) to describe pathway activities. The model-based approach enabled us to hypothesize on the likely emergence (or disappearance) of indirect dosing-dependent regulatory interactions, pointing to likely mechanistic implications of dosing of MPL transcriptional regulation. Both acute and chronic MPL administration induced a strong core of activity within pathway families including the following: lipid metabolism, amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, regulation of essential organelles, and xenobiotic metabolism pathway families. Pathway activities alter between acute and chronic dosing, indicating that MPL response is dosing dependent. Furthermore, because multiple pathway activities are dominant within a single pathway, we observe that pathways cannot be defined by a single response. Instead, pathways are defined by multiple, complex, and temporally related activities corresponding to different subgroups of genes within each pathway.

Whole-ventricular irradiation for intracranial germ cell tumors: Dosimetric comparison of pencil beam scanned protons, intensity-modulated radiotherapy and volumetric-modulated arc therapy.

BACKGROUND: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. METHODS: Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. RESULTS: TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (-35.2%, -32.7%; -35.2%, -33.0%, respectively), cerebellum (-53.7%, -33.1%; -53.6%, -32.7%) and right temporal lobe (-14.5%, -31.9%; -14.7%, -29.9%). The Willis' circle was better protected with PBS-PT than IMRT (-7.1%; -7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. CONCLUSIONS: Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT's superiority over VMAT, thus potentially minimizing long-term sequelae.

Are age and gender suitable matching criteria in organ dose reconstruction using surrogate childhood cancer patients' CT scans?

PURPOSE: The purpose of this work was to assess the feasibility of using surrogate CT scans of matched patients for organ dose reconstructions for childhood cancer (CC) survivors, treated in the past with only 2D imaging data available instead of 3D CT data, and in particular using the current literature standard of matching patients based on similarity in age and gender. METHODS: Thirty-one recently treated CC patients with abdominal CT scans were divided into six age- and gender-matched groups. From each group, two radiotherapy plans for Wilms' tumor were selected as reference plans and applied to the age- and gender-matched patients' CTs in the respective group. Two reconstruction strategies were investigated: S1) without field adjustments; S2) with manual field adjustments according to anatomical information, using a visual check in digitally reconstructed radiographs. To assess the level of agreement between the reconstructed and the reference dose distributions, we computed (using a collapsed cone algorithm) and compared the absolute deviation in mean and maximum dose normalized by the prescribed dose (i.e., normalized errors |NEmean | and |NE2cc |) in eight organs at risk (OARs): heart, lungs, liver, spleen, kidneys, and spinal cord. Furthermore, we assessed the quality of a reconstruction case by varying acceptance thresholds for |NEmean | and |NE2cc |. A reconstruction case was accepted (i.e., considered to pass) if the errors in all OARs are smaller than the threshold. The pass fraction for a given threshold was then defined as the percentage of reconstruction cases that were classified as a pass. Furthermore, we consider the impact of allowing to use a different CT scan for each OAR. RESULTS: Slightly smaller reconstruction errors were achieved with S2 in multiple OARs than with S1 (P < 0.05). Among OARs, the best reconstruction was found for the spinal cord (average |NEmean | and |NE2cc | ≤ 4%). The largest average |NEmean | was found in the spleen (18%). The largest average |NE2cc | was found in the left lung (26%). Less than 30% of the reconstruction cases (i.e., pass fraction) meet the criteria that |NEmean | < 20% and |NE2cc | < 20% in all OARs when using age and gender matching and a single CT to do reconstructions. Allowing other matchings and combining reconstructions for OARs from multiple patients, the pass fraction increases substantially to more than 60%. CONCLUSIONS: To conclude, reconstructions with small deviations can be obtained by using CC patients' CT scans, making the general approach promising. However, using age and gender as the only matching criteria to select a CT scan for the reconstruction is not sufficient to guarantee sufficiently low reconstruction errors. It is therefore suggested to include more features (e.g., height, features extracted from 2D radiographs) than only age and gender for dose reconstruction for CC survivors treated in the pre-3D radiotherapy planning era and to consider ways to combine multiple reconstructions focused on different OARs.