Monte Carlo simulation study of an in vivo four-dimensional tracking system with a diverging collimator for monitoring radiation source (Ir-192) location during brachytherapy: proof of concept and feasibility.

Introduction: The aim of this study was to demonstrate the potential of an in vivo four-dimensional (4D) tracking system to accurately localize the radiation source, Iridium-192 (Ir-192) in high-dose rate brachytherapy. Methods: To achieve time-dependent 3D positioning of the Ir-192 source, we devised a 4D tracking system employing multiple compact detectors. During the system's design phase, we conducted comprehensive optimization and analytical evaluations of the diverging collimator employed for detection purposes. Subsequently, we executed 3D reconstruction and positioning procedures based on the 2D images obtained by six detectors, each equipped with an optimized diverging collimator. All simulations for designing and evaluating the 4D tracking system were performed using the open-source GATE (v9.1) Monte Carlo platform based on the GEANT4 (v10.7) toolkit. In addition, to evaluate the accuracy of the proposed 4D tracking system, we conducted simulations and 3D positioning using a solid phantom and patient data. Finally, the error between the reconstructed position coordinates determined by the tracking system and the original coordinates of the Ir-192 radiation source was analyzed. Results: The parameters for the optimized diverging collimator were a septal thickness of 0.3 mm and a collimator height of 30 mm. A tracking system comprising 6 compact detectors was designed and implemented utilizing this collimator. Analysis of the accuracy of the proposed Ir-192 source tracking system found that the average of the absolute values of the error between the 3D reconstructed and original positions for the simulation with the solid phantom were 0.440 mm for the x coordinate, 0.423 mm for the y coordinate, and 0.764 mm for the z coordinate, and the average Euclidean distance was 1.146 mm. Finally, in a simulation based on data from a patient who underwent brachytherapy, the average Euclidean distance between the original and reconstructed source position was 0.586 mm. Discussion: These results indicated that the newly designed in vivo 4D tracking system for monitoring the Ir-192 source during brachytherapy could determine the 3D position of the radiation source in real time during treatment. We conclude that the proposed positioning system has the potential to make brachytherapy more accurate and reliable.

Study of a plastic scintillating plate-based quality assurance system for pencil beam scanning proton beams.

INTRODUCTION: The purpose of this study was to evaluate a plastic scintillating plate-based beam monitoring system to perform quality assurance (QA) measurements in pencil beam scanning proton beam. METHODS: Single spots and scanned fields were measured with the high-resolution dosimetry system, consisting of a plastic scintillation plate coupled to a camera in a dark box at the isocenter. The measurements were taken at 110-190 MeV beam energies with 30° gantry angle intervals at each energy. Spot positions were determined using the plastic scintillating plate-based dosimetry system at the isocenter for 70-230 MeV beam energies with 30° gantry angle intervals. The effect of gantry angle on dose distribution was also assessed by determining the scanning pattern for daily QA and 25 fields treated with intensity-modulated proton therapy. RESULTS: Spot size, field flatness, and field symmetry of plastic scintillating plate-based dosimetry system were consistent with EBT3 at all investigated energies and angles. In all investigated energies and angles, the spot size measured was ±10% of the average size of each energy, the spot position measured was within ±2 mm, field flatness was within ±2%, and field symmetry was within ±1%. The mean gamma passing rates with the 3%/3 mm gamma criterion of the scanning pattern and 25 fields were 99.2% and 99.8%, respectively. CONCLUSIONS: This system can be effective for QA determinations of spot size, spot position, field flatness, and field symmetry over 360° of gantry rotation in a time- and cost-effective manner, with spatial resolution comparable to that of EBT3 film.

Study of multistep Dense U-Net-based automatic segmentation for head MRI scans.

BACKGROUND: Despite extensive efforts to obtain accurate segmentation of magnetic resonance imaging (MRI) scans of a head, it remains challenging primarily due to variations in intensity distribution, which depend on the equipment and parameters used. PURPOSE: The goal of this study is to evaluate the effectiveness of an automatic segmentation method for head MRI scans using a multistep Dense U-Net (MDU-Net) architecture. METHODS: The MDU-Net-based method comprises two steps. The first step is to segment the scalp, skull, and whole brain from head MRI scans using a convolutional neural network (CNN). In the first step, a hybrid network is used to combine 2.5D Dense U-Net and 3D Dense U-Net structure. This hybrid network acquires logits in three orthogonal planes (axial, coronal, and sagittal) using 2.5D Dense U-Nets and fuses them by averaging. The resultant fused probability map with head MRI scans then serves as the input to a 3D Dense U-Net. In this process, different ratios of active contour loss and focal loss are applied. The second step is to segment the cerebrospinal fluid (CSF), white matter, and gray matter from extracted brain MRI scans using CNNs. In the second step, the histogram of the extracted brain MRI scans is standardized and then a 2.5D Dense U-Net is used to further segment the brain's specific tissues using the focal loss. A dataset of 100 head MRI scans from an OASIS-3 dataset was used for training, internal validation, and testing, with ratios of 80%, 10%, and 10%, respectively. Using the proposed approach, we segmented the head MRI scans into five areas (scalp, skull, CSF, white matter, and gray matter) and evaluated the segmentation results using the Dice similarity coefficient (DSC) score, Hausdorff distance (HD), and the average symmetric surface distance (ASSD) as evaluation metrics. We compared these results with those obtained using the Res-U-Net, Dense U-Net, U-Net++, Swin-Unet, and H-Dense U-Net models. RESULTS: The MDU-Net model showed DSC values of 0.933, 0.830, 0.833, 0.953, and 0.917 in the scalp, skull, CSF, white matter, and gray matter, respectively. The corresponding HD values were 2.37, 2.89, 2.13, 1.52, and 1.53 mm, respectively. The ASSD values were 0.50, 1.63, 1.28, 0.26, and 0.27 mm, respectively. Comparing these results with other models revealed that the MDU-Net model demonstrated the best performance in terms of the DSC values for the scalp, CSF, white matter, and gray matter. When compared with the H-Dense U-Net model, which showed the highest performance among the other models, the MDU-Net model showed substantial improvements in the HD view, particularly in the gray matter region, with a difference of approximately 9%. In addition, in terms of the ASSD, the MDU-Net model outperformed the H-Dense U-Net model, showing an approximately 7% improvements in the white matter and approximately 9% improvements in the gray matter. CONCLUSION: Compared with existing models in terms of DSC, HD, and ASSD, the proposed MDU-Net model demonstrated the best performance on average and showed its potential to enhance the accuracy of automatic segmentation for head MRI scans.

Synergistic effect of TTF and 5-FU combination treatment on pancreatic cancer cells.

The present study investigated the therapeutic potential of combining tumor-treating fields (TTF), a novel cancer treatment modality that employs low-intensity, alternating electric fields, with 5-fluorouracil (5-FU), a standard chemotherapy drug used for treating pancreatic cancer. The HPAF-II and Mia-Paca II pancreatic cancer cell lines were treated with TTF, 5-FU, or their combination. Combination treatment produced a significantly greater inhibitory effect on cancer cell proliferation than each single modality. Furthermore, combination therapy induced a substantially higher rate of pancreatic cancer cell apoptosis and exhibited a synergistic effect in clonogenic assays. Additionally, combination treatment showed a greater inhibition of cancer cell migration and invasion than either TTF or 5-FU alone. In conclusion, these findings suggest that the synergistic properties of TTF and 5-FU result in greater therapeutic efficacy against pancreatic cancer cells than either modality alone and may improve survival rates in patients with pancreatic cancer.

Feasibility study of a scintillation sheet-based detector for fluence monitoring during external photon beam radiotherapy.

PURPOSE: This study evaluated the properties of a scintillation sheet-based dosimetry system for beam monitoring with high spatial resolution, including the effects of this system on the treatment beam. The dosimetric characteristics and feasibility of this system for clinical use were also evaluated. METHODS: The effects of the dosimetry system on the beam were evaluated by measuring the percentage depth doses, dose profiles, and transmission factors. Fifteen treatment plans were created, and the influence of the dosimetry system on these clinical treatment plans was evaluated. The performance of the system was assessed by determining signal linearity, dose rate dependence, and reproducibility. The feasibility of the system for clinical use was evaluated by comparing intensity distributions with reference intensity distributions verified by quality assurance. RESULTS: The spatial resolution of the dosimetry system was found to be 0.43 mm/pixel when projected to the isocenter plane. The dosimetry system attenuated the intensity of 6 MV beams by about 1.1%, without affecting the percentage depth doses and dose profiles. The response of the dosimetry system was linear, independent of the dose rate used in the clinic, and reproducible. Comparison of intensity distributions of evaluation treatment fields with reference intensity distributions showed that the 1%/1 mm average gamma passing rate was 99.6%. CONCLUSIONS: The dosimetry system did not significantly alter the beam characteristics, indicating that the system could be implemented by using only a transmission factor. The dosimetry system is clinically suitable for monitoring treatment beam delivery with higher spatial resolution than other transmission detectors.

Inter-fractional entrance dose monitoring as quality assurance using Gafchromic EBT3 film.

Introduction: This study describes a simple method of inter-fractional photon beam monitoring to measure the entrance dose of radiation treatment using Gafchromic EBT3 film. Materials and Methods: The film was placed at the center of a 1-cm thick phantom shaped like a block tray and fixed on the accessory tray of the gantry. The entrance dose was measured following the placement of the film in the accessory tray. The dose distribution calculated with the treatment planning system was compared with the dose distribution on the irradiated EBT3 films. The effectiveness of this methodology, as determined by gamma passing rates, was evaluated for the 22 fields of eight three-dimensional conformal radiotherapy (3D-CRT) plans and the 41 fields of nine intensity-modulated radiotherapy (RT) plans. The plans for three-dimensional conformal RT included treatments of the rectum, liver, breast, and head and neck, whereas the plans for intensity-modulated RT included treatments of the liver, brain, and lung. Results: The gamma passing rates for 3D-CRT ranged from 96.4% to 99.5%, with the mean gamma passing rate for 22 fields being 98.0%. The gamma passing rate for intensity-modulated RT ranged from 96.1% to 98.9%, with the mean gamma passing rate for 41 fields being 97.7%. All gamma indices were over the 95% tolerance level. Conclusions: The methodology described in this study, based on Gafchromic EBT3 film, can be utilized for inter-fractional entrance dose monitoring as quality assurance during RT. Clinical application of this method to patients can verify the accuracy of beam delivery in the treatment room.

Technical note: Evaluation of methods for reducing edge current density under electrode arrays for tumor-treating fields therapy.

BACKGROUND: Tumor-treating fields (TTFields) therapy is increasingly utilized clinically because of its demonstrated efficacy in cancer treatment. However, the risk of skin burns must still be reduced to improve patient safety and posttreatment quality of life. PURPOSE: The purpose of this study was to evaluate the methods of constructing electrode arrays that reduce current density exceeding threshold values, which can cause skin burns during TTFields therapy. METHODS: Electrode and body models were generated using COMSOL software. The body model had the dielectric properties of the scalp. The average current density beneath the central region of the electrode was maintained at ∼31 mA/cm2 RMS. The deviations in current density at the edges of the electrode were reduced by three methods: adjustment of the ceramic thickness ratio of the center to the edge from 1/5 to 4/5, adjustment of the radius of the metal plate from 5.0 to 8.0 mm, and insertion of an insulator of width 0.5 to 2 mm at the edge. RESULTS: While using a single circular electrode, adjustment of the ceramic thickness ratio, adjustment of the metal plate radius, and insertion of an insulator near the edge reduced the deviations of current density by 14.6%, 67.7%, and 75.3%, respectively. Similarly, while using circular electrode arrays, inserting an insulator at the edge of each electrode reduced the deviations of current density significantly, from 8.62 to 2.40 mA/cm2 . CONCLUSIONS: Insertion of an insulator at the edge of each electrode was found to be the most effective method of attaining uniform current density distribution beneath the electrode, thereby lowering the risk of adverse effects of TTFields therapy.

Development of a dosimetry system for therapeutic X-rays using a flexible amorphous silicon thin-film solar cell with a scintillator screen.

PURPOSE: To evaluate the dosimetric characteristics and applications of a dosimetry system composed of a flexible amorphous silicon thin-film solar cell and scintillator screen (STFSC-SS) for therapeutic X-rays. METHODS: The real-time dosimetry system was composed of a flexible a-Si thin-film solar cell (0.2-mm thick), a scintillator screen to increase its efficiency, and an electrometer to measure the generated charge. The dosimetric characteristics of the developed system were evaluated including its energy dependence, dose linearity, and angular dependence. Calibration factors for the signal measured by the system and absorbed dose-to-water were obtained by setting reference conditions. The application and correction accuracy of the developed system were evaluated by comparing the absorbed dose-to-water measured using a patient treatment beam with that measured using the ion chamber. RESULTS: The responses of STFSC-SS to energy, field size, depth, and source-to-surface distance (SSD) were more dependent on measurement conditions than were the responses of the ion chamber, although the former dependence was due to the scintillator screen, not the solar cell. The signals of STFSC-SS were also dependent on dose rate, while the responses of solar cell alone and scintillator screen were not dependent on dose rate. The scintillator screen reduced the output of solar cell at 6 and 15 MV by 0.60 and 0.55%, respectively. The different absorbed dose-to-water measured using STFSC-SS for patient treatment beam differed by 0.4% compared to those measured using the ionization chamber. The uncertainties of the developed system for 6 and 15 MV photon beams were 1.8 and 1.7%, respectively, confirming the accuracy and applicability of this system. CONCLUSIONS: The thin-film solar cell-based detector developed in this study can accurately measure absorbed dose-to-water. The increased signal resulting from the use of the scintillator screen is advantageous for measuring low doses and stable signal output. In addition, this system is flexible, making it applicable to curved surfaces, such as a patient's body, and is cost-effective.

The combination of tumor treating fields and hyperthermia has synergistic therapeutic effects in glioblastoma cells by downregulating STAT3.

Glioblastoma multiforme (GBM), the most common type of brain tumor, is a very aggressive and treatment-refractory cancer, with a 5-year survival rate of approximately 5%. Hyperthermia (HT) and tumor treating fields (TTF) therapy have been used to treat cancer, either alone or in combination with other treatment methods. Both treatments have been reported to increase the efficacy of other treatment techniques and to improve patient prognosis. The present study evaluated the therapeutic effects of combining HT and TTF on GBM cell lines. Cells were subjected to HT, TTF, HT+TTF, or neither treatment, followed by comparisons of cell proliferation, apoptosis, migration and invasiveness. Clonogenic assays showed that the two treatments had a synergistic effect. The levels of cleaved PARP and cleaved caspase-3 were higher and apoptosis was increased in cells treated with HT+TTF than in cells treated with HT or TTF alone. In addition, HT+TTF showed greater inhibition of GBM cell migration and invasiveness and greater downregulation of STAT3 than either HT or TTF alone. The stronger anticancer effect of HT+TTF suggested that this combination treatment can increase the survival rate of patients with difficult-to-treat cancers such as GBM.

Thymidine decreases the DNA damage and apoptosis caused by tumor-treating fields in cancer cell lines.

BACKGROUND: Tumor-treating fields (TTFields) is an emerging non-invasive cancer-treatment modality using alternating electric fields with low intensities and an intermediate range of frequency. TTFields affects an extensive range of charged and polarizable cellular factors known to be involved in cell division. However, it causes side-effects, such as DNA damage and apoptosis, in healthy cells. OBJECTIVE: To investigate whether thymidine can have an effect on the DNA damage and apoptosis, we arrested the cell cycle of human glioblastoma cells (U373) at G1/S phase by using thymidine and then exposed these cells to TTFields. METHODS: Cancer cell lines and normal cell (HaCaT) were arrested by thymidine double block method. Cells were seeded into the gap of between the insulated wires. The exposed in alternative electric fields at 120 kHz, 1.2 V/cm. They were counted the cell numbers and analyzed for cancer malignant such as colony formation, Annexin V/PI staining, γH2AX and RT-PCR. RESULTS: The colony-forming ability and DNA damage of the control cells without thymidine treatment were significantly decreased, and the expression levels of BRCA1, PCNA, CDC25C, and MAD2 were distinctly increased. Interestingly, however, cells treated with thymidine did not change the colony formation, apoptosis, DNA damage, or gene expression pattern. CONCLUSIONS: These results demonstrated that thymidine can inhibit the TTFields-caused DNA damage and apoptosis, suggesting that combining TTFields and conventional treatments, such as chemotherapy, may enhance prognosis and decrease side effects compared with those of TTFields or conventional treatments alone.

Utility of fast non-local means (FNLM) filter for detection of pulmonary nodules in chest CT for pediatric patient.

PURPOSE: This study was aimed to evaluate the utility based on imaging quality of the fast non-local means (FNLM) filter in diagnosing lung nodules in pediatric chest computed tomography (CT). METHODS: We retrospectively reviewed the chest CT reconstructed with both filtered back projection (FBP) and iterative reconstruction (IR) in pediatric patients with metastatic lung nodules. After applying FNLM filter with six h values (0.0001, 0.001, 0.01, 0.1, 1, and 10) to the FBP images, eight sets of images including FBP, IR, and FNLM were analyzed. The image quality of the lung nodules was evaluated objectively for coefficient of variation (COV), contrast to noise ratio (CNR), and point spread function (PSF), and subjectively for noise, sharpness, artifacts, and diagnostic acceptability. RESULTS: The COV was lowest in IR images and decreased according to increasing h values and highest with FBP images (P < 0.001). The CNR was highest with IR images, increased according to increasing h values and lowest with FBP images (P < 0.001). The PSF was lower only in FNLM filter with h value of 0.0001 or 0.001 than in IR images (P < 0.001). In subjective analysis, only images of FNLM filter with h value of 0.0001 or 0.001 rarely showed unacceptable quality and had comparable results with IR images. There were less artifacts in FNLM images with h value of 0.0001 compared with IR images (p < 0.001). CONCLUSION: FNLM filter with h values of 0.0001 allows comparable image quality with less artifacts compared with IR in diagnosing metastatic lung nodules in pediatric chest CT.

Sensitivity of radio-photoluminescence glass dosimeters to accumulated doses.

BACKGROUND: This study investigated the effect of accumulated doses on radio-photoluminescence glass dosimeters (RPLGDs) from measurements involving mega-voltage photons. METHODS: Forty-five commercially available RPLGDs were irradiated to estimate their dose responses. Photon beams of 6, 10, and 15 MV were irradiated onto the RPLGDs inside a phantom, which were divided into five groups with different doses and energies. Groups 1 and 2 were irradiated at 1, 5, 10, 50, and 100 Gy in a sequential manner; Group 3 was irradiated 10 times with a dose of 10 Gy; and Groups 4 and 5 followed the same method as that of Group 3, but with doses of 50 Gy and 100 Gy, respectively. Each device was subjected to a measurement reading procedure each time irradiation. RESULTS: For the annealed Group 1, RPLGD exhibited a linearity response with variance within 5%. For the non-annealed Group 2, readings demonstrated hyperlinearity at 6 MV and 10 MV, and linearity at 15 MV. Following the 100 Gy irradiation, the readings for Group 2 were 118.7 ± 1.9%, 112.2 ± 2.7%, and 101.5 ± 2.3% at 6, 10, and 15 MV, respectively. For Groups 3, 4, and 5, the responsiveness of the RPLGDs gradually decreased as the number of repeated irradiations increased. The percentage readings for the 10th beam irradiation with respect to the readings for the primary beam irradiation were 84.6 ± 1.9%, 87.5 ± 2.4%, and 93.0 ± 3.0% at 6 MV, 10 MV, and 15 MV, respectively. CONCLUSIONS: The non-annealed RPLGD response to dose was hyperlinear for the 6 MV and 10 MV photon beams but not for the 15 MV photon beam. Additionally, the annealed RPLGD exhibited a fading phenomenon when the measurement was repeated several times and demonstrated a relatively large fading effect at low energies than at high energies.

Tumor treating fields (TTF) treatment enhances radiation-induced apoptosis in pancreatic cancer cells.

PURPOSE: Tumor treating fields (TTF) therapy is a noninvasive method that uses alternating electric fields to treat various types of cancer. This study demonstrates the combined effect of TTF and radiotherapy (RT) in vitro on pancreatic cancer, which is known to be difficult to treat. MATERIALS AND METHODS: In CFPAC-I and HPAF-II pancreatic cancer cell lines, the combined in vitro effect of TTF and RT was evaluated by measuring cell counts, markers of apoptosis, and clonogenic cell survival. The synergy effects were verified using the Valeriote and Carpentier equations. RESULTS: TTF and RT inhibited cancer cell growth more effectively than did monotherapy with TTF or RT. The combined treatment also enhanced apoptosis more than monotherapy, as shown by assays for cleaved poly (ADP-ribose) polymerase (PARP) and annexin V. In addition, on the survival curve, this treatment method has been shown to work synergistically. CONCLUSION: These results suggest that combined treatment with TTF and RT may be a good alternative treatment for patients with pancreatic cancer.

Clinical application of a gantry-attachable plastic scintillating plate dosimetry system in pencil beam scanning proton therapy beam monitoring.

PURPOSE: The entrance beam fluence of therapeutic proton scanning beams can be monitored using a gantry-attachable plastic scintillating plate (GAPSP). This study evaluated the clinical application of the GAPSP using a method that measures intensity modulated proton therapy (IMPT) beams for patient treatment. METHODS: IMPT beams for the treatment of nine patients, at sites that included the spine, head and neck, pelvis, and lung, were measured using the GAPSP, composed of an EJ-212 plastic scintillator and a CMOS camera. All energy layers distinguished by the GAPSP were accumulated to determine the dose distribution of the treatment field. The evaluated fields were compared with reference dose maps verified by quality assurance. RESULTS: Comparison of dose distributions of evaluation treatment fields with reference dose distributions showed that the 3%/1 mm average gamma passing rate was 96.4%, independent of the treatment site, energy range and field size. When dose distributions were evaluated using the same criteria for each energy layer, the average gamma passing rate was 91.7%. CONCLUSIONS: The GAPSP is a suitable, low-cost method for monitoring pencil beam scanning proton therapy, especially for non-spot scanning or additional collimation. The GAPSP can also estimate the treatment beam by the energy layer, a feature not common to other proton dosimetry tools.

Feasibility study of a plastic scintillating plate-based treatment beam fluence monitoring system for use in pencil beam scanning proton therapy.

PURPOSE: The purpose of this study was to describe a plastic scintillating plate-based gantry-attachable dosimetry system for pencil beam scanning proton therapy to monitor entrance proton beam fluence, and to evaluate the dosimetric characteristics of this system and its feasibility for clinical use. METHODS: The dosimetry system, consisting of a plastic scintillating plate and a CMOS camera, was attached to a dedicated scanning nozzle and scintillation during proton beam irradiation was recorded. Dose distribution was calculated from the accumulated recorded frames. The dosimetric characteristics (energy dependency, dose linearity, dose rate dependency, and reproducibility) of the gantry-attachable dosimetry system for use with therapeutic proton beams were measured, and the feasibility of this system during clinical use was evaluated by determining selected quality assurance items at our institution. RESULTS: The scintillating plate shortened the range of the proton beam by the water-equivalent thickness of the plate and broadened the spatial profile of the single proton spot by 11% at 70 MeV. The developed system functioned independently of the beam energy (<1.3%) and showed dose linearity, and also functioned independently of the dose rate. The feasibility of the system for clinical use was evaluated by comparing the measured quality assurance dose distribution to that of the treatment planning system. The gamma passing rate with a criterion of 3%/3 mm was 97.58%. CONCLUSIONS: This study evaluated the dosimetric characteristics of a plastic scintillating plate-based dosimetry system for use with scanning proton beams. The ability to account for the interference of the dosimetry system on the therapeutic beam enabled offline monitoring of the entrance beam fluence of the pencil beam scanning proton therapy independent of the treatment system with high resolution and in a cost-effective manner.

Feasibility of a GATE Monte Carlo platform in a clinical pretreatment QA system for VMAT treatment plans using TrueBeam with an HD120 multileaf collimator.

PURPOSE: To evaluate the quality of patient-specific complicated treatment plans, including commercialized treatment planning systems (TPS) and commissioned beam data, we developed a process of quality assurance (QA) using a Monte Carlo (MC) platform. Specifically, we constructed an interface system that automatically converts treatment plan and dose matrix data in digital imaging and communications in medicine to an MC dose-calculation engine. The clinical feasibility of the system was evaluated. MATERIALS AND METHODS: A dose-calculation engine based on GATE v8.1 was embedded in our QA system and in a parallel computing system to significantly reduce the computation time. The QA system automatically converts parameters in volumetric-modulated arc therapy (VMAT) plans to files for dose calculation using GATE. The system then calculates dose maps. Energies of 6 MV, 10 MV, 6 MV flattening filter free (FFF), and 10 MV FFF from a TrueBeam with HD120 were modeled and commissioned. To evaluate the beam models, percentage depth dose (PDD) values, MC calculation profiles, and measured beam data were compared at various depths (Dmax , 5 cm, 10 cm, and 20 cm), field sizes, and energies. To evaluate the feasibility of the QA system for clinical use, doses measured for clinical VMAT plans using films were compared to dose maps calculated using our MC-based QA system. RESULTS: A LINAC QA system was analyzed by PDD and profile according to the secondary collimator and multileaf collimator (MLC). Values for MC calculations and TPS beam data obtained using CC13 ion chamber (IBA Dosimetry, Germany) were consistent within 1.0%. Clinical validation using a gamma index was performed for VMAT treatment plans using a solid water phantom and arbitrary patient data. The gamma evaluation results (with criteria of 3%/3 mm) were 98.1%, 99.1%, 99.2%, and 97.1% for energies of 6 MV, 10 MV, 6 MV FFF, and 10 MV FFF, respectively. CONCLUSIONS: We constructed an MC-based QA system for evaluating patient treatment plans and evaluated its feasibility in clinical practice. We observed robust agreement between dose calculations from our QA system and measurements for VMAT plans. Our QA system could be useful in other clinical settings, such as small-field SRS procedures or analyses of secondary cancer risk, for which dose calculations using TPS are difficult to verify.

Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells.

Tumor-treating fields (TTFs) - a type of electromagnetic field-based therapy using low-intensity electrical fields - has recently been characterized as a potential anticancer therapy for glioblastoma multiforme (GBM). However, the molecular mechanisms involved remain poorly understood. Our results show that the activation of autophagy contributes to the TTF-induced anti-GBM activity in vitro or in vivo and GBM patient stem cells or primary in vivo culture systems. TTF-treatment upregulated several autophagy-related genes (~2-fold) and induced cytomorphological changes. TTF-induced autophagy in GBM was associated with decreased Akt2 expression, not Akt1 or Akt3, via the mTOR/p70S6K pathway. An Affymetrix GeneChip miRNA 4.0 Array analysis revealed that TTFs altered the expression of many microRNAs (miRNAs). TTF-induced autophagy upregulated miR-29b, which subsequently suppressed the Akt signaling pathway. A luciferase reporter assay confirmed that TTFs induced miR-29b to target Akt2, negatively affecting Akt2 expression thereby triggering autophagy. TTF-induced autophagy suppressed tumor growth in GBM mouse models subjected to TTFs as determined by positron emission tomography and computed tomography (PET-CT). GBM patient stem cells and a primary in vivo culture system with high Akt2 levels also showed TTF-induced inhibition. Taken together, our results identified autophagy as a critical cell death pathway triggered by TTFs in GBM and indicate that TTF is a potential treatment option for GBM.

Feasibility of fast non local means filter in pediatric chest x-ray for increasing of pulmonary nodule detectability with 3D printed lung nodule phantom.

General x-ray images have a lower probability of nodule detection than other modalities. Especially in children, the probability of nodule detection can likely drop due to poor image quality from using low radiation dose. To demonstrate the effectiveness of fast non-local means (FNLM) filter to increase the probability of nodule detection in pediatric chest x-ray images and reduce radiation dose while maintaining image quality. Quantitative assessment of normalised noise power spectrum (NNPS), coefficient of variation (COV) and contrast to noise ratio (CNR) were performed after applying four filters (median, Wiener, total variation and FNLM) on a 1-year-old child phantom. A 3D-printed patient nodule phantom was inserted into the phantom. Assessment was performed on AP and LAT view images acquired with the tube voltage reduced to 38 and 27%, and tube current reduced to 84 and 61%, respectively. The results showed the lowest NNPS and COV values and the highest CNR value when the FNLM filter applied. Moreover, the AP view results showed 37% decrease in COV and 30% increase in CNR in images with the FNLM filter applied (images exposed with the tube voltage and current reduced to 29% and 50%, respectively). The LAT view results showed 5% decrease in COV and 36% increase in CNR in images with the FNLM filter applied (images exposed with the tube current reduced by 27%). By applying the FNLM filter, the probability of nodule detection could be increased by denoising and contrast enhancement. Moreover, using the FNLM filter could reduce cancer risk in pediatric patients by reducing radiation dose about 30% to 44%.

Effectiveness of a Fractionated Therapy Scheme in Tumor Treating Fields Therapy.

This study aimed to evaluate the biological effectiveness of cancer therapy with tumor treating fields using a fractionated treatment scheme that was originally designed for radiotherapy. Discontinuous fractional tumor treating fields of an intensity of 0.9 to 1.2 V/cm and a frequency of 150 KHz were applied to U373 cancer cells and IEC6 normal cells for 3 days, with durations of 3, 6, 12, or 24 h/d. As the treatment duration of the tumor treating fields increased from 3 to 24 h/d, the relative tumor cell (U373) number (% of control) reduced in proportion to the treatment duration. Compared to a 25% cell number reduction (75% of control) for the group of 6 h/d treatment at 1.2 V/cm, only 5% (70% of control) and 8% (67% of control) of additional reductions were observed for the group of 12 and 24 h/d treatment, respectively. This experimental result indicates that the dependence on treatment duration in tumor cell inhibition was weakened distinctly at treatment duration over 6 h/d. For normal cells (IEC6), the relative cell number corresponding to the treatment time of the tumor treating fields at 1.2 V/cm of electric field strength was not decreased much for the treatment times of 3, 6, and 12 h/d, revealing 93.3%, 90.0%, and 89.3% relative cell numbers, respectively, but it suddenly decreased to ∼73% for the 24 h/d treatment. Our results showed that the effects of tumor treating fields on tumor cells were higher than on normal cells for treatment duration of 3 to 12 h/d, but the difference became minimal for treatment duration of 24 h/d. The fractionated scheme, using tumor treating fields, reduced the treatment time while maintaining efficacy, suggesting that this method may be clinically applicable for cancer treatment.

Functional Biological Activity of Sorafenib as a Tumor-Treating Field Sensitizer for Glioblastoma Therapy.

Glioblastoma, the most common primary brain tumor in adults, is an incurable malignancy with poor short-term survival and is typically treated with radiotherapy along with temozolomide. While the development of tumor-treating fields (TTFields), electric fields with alternating low and intermediate intensity has facilitated glioblastoma treatment, clinical outcomes of TTFields are reportedly inconsistent. However, combinatorial administration of chemotherapy with TTFields has proven effective for glioblastoma patients. Sorafenib, an anti-proliferative and apoptogenic agent, is used as first-line treatment for glioblastoma. This study aimed to investigate the effect of sorafenib on TTFields-induced anti-tumor and anti-angiogenesis responses in glioblastoma cells in vitro and in vivo. Sorafenib sensitized glioblastoma cells to TTFields, as evident from significantly decreased post-TTFields cell viability (p < 0.05), and combinatorial treatment with sorafenib and TTFields accelerated apoptosis via reactive oxygen species (ROS) generation, as evident from Poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, use of sorafenib plus TTFields increased autophagy, as evident from LC3 upregulation and autophagic vacuole formation. Cell cycle markers accumulated, and cells underwent a G2/M arrest, with an increased G0/G1 cell ratio. In addition, the combinatorial treatment significantly inhibited tumor cell motility and invasiveness, and angiogenesis. Our results suggest that combination therapy with sorafenib and TTFields is slightly better than each individual therapy and could potentially be used to treat glioblastoma in clinic, which requires further studies.