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.

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%.

Development of Optical Fiber Based Measurement System for the Verification of Entrance Dose Map in Pencil Beam Scanning Proton Beam.

This study describes the development of a beam monitoring system for the verification of entrance dose map in pencil beam scanning (PBS) proton therapy based on fiber optic radiation sensors (FORS) and the validation of this system through a feasibility study. The beam monitoring system consisted of 128 optical fibers optically coupled to photo-multiplier tubes. The performance of the beam monitoring system based on FORS was verified by comparing 2D dose maps of square-shaped fields of various sizes, which were obtained using conventional dosimeters such as MatriXX and EBT3 film, with those measured using FORS. The resulting full-width at half maximum and penumbra were compared for PBS proton beams, with a ≤2% difference between each value, indicating that measurements using the conventional dosimetric tool corresponded to measurements based on FORS. For irregularly-shaped fields, a comparison based on the gamma index between 2D dose maps obtained using MatriXX and EBT3 film and the 2D dose map measured by the FORS showed passing rates of 96.9 ± 1.3% and 96.2 ± 1.9%, respectively, confirming that FORS-based measurements for PBS proton therapy agreed well with those measured using the conventional dosimetric tools. These results demonstrate that the developed beam monitoring system based on FORS is good candidate for monitoring the entrance dose map in PBS proton therapy.

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.

Secondary cancer-incidence risk estimates for external radiotherapy and high-dose-rate brachytherapy in cervical cancer: phantom study.

This study was designed to estimate radiation-induced secondary cancer risks from high-dose-rate (HDR) brachytherapy and external radiotherapy for patients with cervical cancer based on measurements of doses absorbed by various organs. Organ doses from HDR brachytherapy and external radiotherapy were measured using glass rod dosimeters. Doses to out-of-field organs were measured at various loca-tions inside an anthropomorphic phantom. Brachytherapy-associated organ doses were measured using a specialized phantom that enabled applicator insertion, with the pelvis portion of the existing anthropomorphic phantom replaced by this new phantom. Measured organ doses were used to calculate secondary cancer risk based on Biological Effects of Ionizing Radiation (BEIR) VII models. In both treatment modalities, organ doses per prescribed dose (PD) mostly depended on the distance between organs. The locations showing the highest and lowest doses were the right kidney (external radiotherapy: 215.2 mGy; brachytherapy: 655.17 mGy) and the brain (external radiotherapy: 15.82 mGy; brachytherapy: 2.49 mGy), respectively. Organ doses to nearby regions were higher for brachytherapy than for external beam therapy, whereas organ doses to distant regions were higher for external beam therapy. Organ doses to distant treatment regions in external radiotherapy were due primarily to out-of-field radiation resulting from scattering and leakage in the gantry head. For brachytherapy, the highest estimated lifetime attributable risk per 100,000 population was to the stomach (88.6), whereas the lowest risks were to the brain (0.4) and eye (0.4); for external radiotherapy, the highest and lowest risks were to the thyroid (305.1) and brain (2.4). These results may help provide a database on the impact of radiotherapy-induced secondary cancer incidence dur-ing cervical cancer treatment, as well as suggest further research on strategies to counteract the risks of radiotherapy-associated secondary malignancies.

A comparison of the quality assurance of four dosimetric tools for intensity modulated radiation therapy.

BACKGROUND: This study was designed to compare the quality assurance (QA) results of four dosimetric tools used for intensity modulated radiation therapy (IMRT) and to suggest universal criteria for the passing rate in QA, irrespective of the dosimetric tool used. MATERIALS AND METHODS: Thirty fields of IMRT plans from five patients were selected, followed by irradiation onto radiochromic film, a diode array (Mapcheck), an ion chamber array (MatriXX) and an electronic portal imaging device (EPID) for patient-specific QA. The measured doses from the four dosimetric tools were compared with the dose calculated by the treatment planning system. The passing rates of the four dosimetric tools were calculated using the gamma index method, using as criteria a dose difference of 3% and a distance-to-agreement of 3 mm. RESULTS: The QA results based on Mapcheck, MatriXX and EPID showed good agreement, with average passing rates of 99.61%, 99.04% and 99.29%, respectively. However, the average passing rate based on film measurement was significantly lower, 95.88%. The average uncertainty (1 standard deviation) of passing rates for 6 intensity modulated fields was around 0.31 for film measurement, larger than those of the other three dosimetric tools. CONCLUSIONS: QA results and consistencies depend on the choice of dosimetric tool. Universal passing rates should depend on the normalization or inter-comparisons of dosimetric tools if more than one dosimetric tool is used for patient specific QA.

Radiotherapy-induced secondary cancer risk for breast cancer: 3D conformal therapy versus IMRT versus VMAT.

This study evaluated the secondary cancer risk to various organs due to radiation treatment for breast cancer. Organ doses to an anthropomorphic phantom were measured using a photoluminescent dosimeter (PLD) for breast cancer treatment with 3D conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Cancer risk based on the measured dose was calculated using the BEIR (Biological Effects of Ionizing Radiation) VII models. The secondary dose per treatment dose (50.4 Gy) to various organs ranged from 0.02 to 0.36 Gy for 3D-CRT, but from 0.07 to 8.48 Gy for IMRT and VMAT, indicating that the latter methods are associated with higher secondary radiation doses than 3D-CRT. The result of the homogeneity index in the breast target shows that the dose homogeneity of 3D-CRT was worse than those of IMRT and VMAT. The organ specific lifetime attributable risks (LARs) to the thyroid, contralateral breast and ipsilateral lung per 100 000 population were 0.02, 19.71, and 0.76 respectively for 3D-CRT, much lower than the 0.11, 463.56, and 10.59 respectively for IMRT and the 0.12, 290.32, and 12.28 respectively for VMAT. The overall estimation of LAR indicated that the radiation-induced cancer risk due to breast radiation therapy was lower with 3D-CRT than with IMRT or VMAT.

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.

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.

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.

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.

Eye tracking and gating system for proton therapy of orbital tumors.

PURPOSE: A new motion-based gated proton therapy for the treatment of orbital tumors using real-time eye-tracking system was designed and evaluated. METHODS: We developed our system by image-pattern matching, using a normalized cross-correlation technique with LabVIEW 8.6 and Vision Assistant 8.6 (National Instruments, Austin, TX). To measure the pixel spacing of an image consistently, four different calibration modes such as the point-detection, the edge-detection, the line-measurement, and the manual measurement mode were suggested and used. After these methods were applied to proton therapy, gating was performed, and radiation dose distributions were evaluated. RESULTS: Moving phantom verification measurements resulted in errors of less than 0.1 mm for given ranges of translation. Dosimetric evaluation of the beam-gating system versus nongated treatment delivery with a moving phantom shows that while there was only 0.83 mm growth in lateral penumbra for gated radiotherapy, there was 4.95 mm growth in lateral penumbra in case of nongated exposure. The analysis from clinical results suggests that the average of eye movements depends distinctively on each patient by showing 0.44 mm, 0.45 mm, and 0.86 mm for three patients, respectively. CONCLUSIONS: The developed automatic eye-tracking based beam-gating system enabled us to perform high-precision proton radiotherapy of orbital tumors.

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.

Accuracy of an automatic patient-positioning system based on the correlation of two edge images in radiotherapy.

We have clinically evaluated the accuracy of an automatic patient-positioning system based on the image correlation of two edge images in radiotherapy. Ninety-six head & neck images from eight patients undergoing proton therapy were compared with a digitally reconstructed radiograph (DRR) of planning CT. Two edge images, a reference image and a test image, were extracted by applying a Canny edge detector algorithm to a DRR and a 2D X-ray image, respectively, of each patient before positioning. In a simulation using a humanoid phantom, performed to verify the effectiveness of the proposed method, no registration errors were observed for given ranges of rotation, pitch, and translation in the x, y, and z directions. For real patients, however, there were discrepancies between the automatic positioning method and manual positioning by physicians or technicians. Using edged head coronal- and sagittal-view images, the average differences in registration between these two methods for the x, y, and z directions were 0.11 cm, 0.09 cm and 0.11 cm, respectively, whereas the maximum discrepancies were 0.34 cm, 0.38 cm, and 0.50 cm, respectively. For rotation and pitch, the average registration errors were 0.95° and 1.00°, respectively, and the maximum errors were 3.6° and 2.3°, respectively. The proposed automatic patient-positioning system based on edge image comparison was relatively accurate for head and neck patients. However, image deformation during treatment may render the automatic method less accurate, since the test image many differ significantly from the reference image.

Estimation of the secondary cancer risk induced by diagnostic imaging radiation during proton therapy.

We have estimated the secondary cancer risk (SCR) introduced by image-guided procedures during proton therapy. The physical dose from imaging radiation and the corresponding organ equivalent dose were calculated for the case of a lumbar spine patient. The maximum physical dose delivered to the patient during the imaging procedure was estimated to be ~0.35% of the prescribed dose of 46 Gy. However, this small imaging dose substantially raised the radiation-induced SCR by ~8%. In addition, the clinical benefit (improved accuracy during the procedure) and costs (extra SCR) associated with image-guided procedures were quantitatively modelled by systematically investigating the changes in SCR as a function of the prescribed dose, treatment target volume and imaging field size. The results showed that the SCR varied sensitively with the volume receiving the imaging and the therapeutic radiation, whereas the SCR depended to a lesser extent on the magnitude of the applied therapeutic radiation. These results showed that the additional SCR introduced by imaging radiation could be efficiently reduced by minimizing the imaging field size during image-guided procedures.

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.