Dose Calculation Accuracy of Beam Models in RadCalc for a 1.5 T MR-Linac.

The purpose of this study is to evaluate RadCalc, an independent dose verification software, for patient-specific quality assurance (PSQA) in online adaptive planning with a magnetic resonance linear accelerator (MR-linac) of a 1.5 T. Version 7.1.4 of RadCalc to introduce the capability to establish a beam model that incorporates MR field characteristics. A total of six models were established, with one using manufacturer-provided data and the others differing in percentage depth dose (PDD) data sources. Overall, two models utilized PDD data from the treatment planning system (TPS), and three used commissioned PDD data from gantry angles of 0° and 270°. Simple tests on a virtual water phantom assessed dose-calculation accuracy, revealing percentage differences ranging from -0.5% to -20.6%. Excluding models with significant differences, clinical tests on 575 adaptive plans (prostate, liver, and breast) showed percentage differences of -0.51%, 1.12%, and 4.10%, respectively. The doses calculated using RadCalc demonstrated similar trends to those of the PSQA-based measurements. The newly released version of RadCalc enables beam modeling that considers the characteristics of the 1.5 T magnetic field. The accuracy of the software in calculating doses at 1.5 T magnetic fields has been verified, thereby making it a reliable and effective tool for PSQA in adaptive plans.

Optimal planning target margin for prostate radiotherapy based on interfractional and intrafractional variability assessment during 1.5T MRI-guided radiotherapy.

Introduction: We analyzed daily pre-treatment- (PRE) and real-time motion monitoring- (MM) MRI scans of patients receiving definitive prostate radiotherapy (RT) with 1.5 T MRI guidance to assess interfractional and intrafractional variability of the prostate and suggest optimal planning target volume (PTV) margin. Materials and methods: Rigid registration between PRE-MRI and planning CT images based on the pelvic bone and prostate anatomy were performed. Interfractional setup margin (SM) and interobserver variability (IO) were assessed by comparing the centroid values of prostate contours delineated on PRE-MRIs. MM-MRIs were used for internal margin (IM) assessment, and PTV margin was calculated using the van Herk formula. Results: We delineated 400 prostate contours on PRE-MRI images. SM was 0.57 ± 0.42, 2.45 ± 1.98, and 2.28 ± 2.08 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively, after bone localization and 0.76 ± 0.57, 1.89 ± 1.60, and 2.02 ± 1.79 mm in the LR, AP, and SI directions, respectively, after prostate localization. IO was 1.06 ± 0.58, 2.32 ± 1.08, and 3.30 ± 1.85 mm in the LR, AP, and SI directions, respectively, after bone localization and 1.11 ± 0.55, 2.13 ± 1.07, and 3.53 ± 1.65 mm in the LR, AP, and SI directions, respectively, after prostate localization. Average IM was 2.12 ± 0.86, 2.24 ± 1.07, and 2.84 ± 0.88 mm in the LR, AP, and SI directions, respectively. Calculated PTV margin was 2.21, 5.16, and 5.40 mm in the LR, AP, and SI directions, respectively. Conclusions: Movements in the SI direction were the largest source of variability in definitive prostate RT, and interobserver variability was a non-negligible source of margin. The optimal PTV margin should also consider the internal margin.

Factors Affecting Zero-Waste Behaviours of College Students.

This study evaluated the recognition and attitude toward microplastic and zero waste among college students and investigated the factors influencing their zero-waste behaviours. The study was conducted from 20 August 2021 to 10 September 2021, including students at a university in G metropolitan city, Republic of Korea. A total of 196 data were analysed. Statements were developed to verify how the use of disposables and the recognition, attitude, and behaviours related to zero waste were affected during the COVID-19 pandemic. Family type and usage of disposables were the factors affecting zero-waste behaviour in Model 1. In Model 2, which included the subcategory of zero-waste recognition, the health effects of microplastics and environmental preservation were significant factors. In Model 3, which included the subcategory of zero-waste attitude, the health effects of microplastics (ß = 0.149, p = 0.016), use of eco-friendly products (ß = 0.342, p < 0.001), and environmental preservation (ß = 0.317, p < 0.001) were significant factors. The use of plastic products increased dramatically during the COVID-19 pandemic. Research and education are needed to promote zero-waste behaviours with a focus on microplastics. Raising awareness of the health effects of microplastics can enhance the effectiveness of education.

Impact of Denoising on Deep-Learning-Based Automatic Segmentation Framework for Breast Cancer Radiotherapy Planning.

Objective: This study aimed to investigate the segmentation accuracy of organs at risk (OARs) when denoised computed tomography (CT) images are used as input data for a deep-learning-based auto-segmentation framework. Methods: We used non-contrast enhanced planning CT scans from 40 patients with breast cancer. The heart, lungs, esophagus, spinal cord, and liver were manually delineated by two experienced radiation oncologists in a double-blind manner. The denoised CT images were used as input data for the AccuContourTM segmentation software to increase the signal difference between structures of interest and unwanted noise in non-contrast CT. The accuracy of the segmentation was assessed using the Dice similarity coefficient (DSC), and the results were compared with those of conventional deep-learning-based auto-segmentation without denoising. Results: The average DSC outcomes were higher than 0.80 for all OARs except for the esophagus. AccuContourTM-based and denoising-based auto-segmentation demonstrated comparable performance for the lungs and spinal cord but showed limited performance for the esophagus. Denoising-based auto-segmentation for the liver was minimal but had statistically significantly better DSC than AccuContourTM-based auto-segmentation (p < 0.05). Conclusions: Denoising-based auto-segmentation demonstrated satisfactory performance in automatic liver segmentation from non-contrast enhanced CT scans. Further external validation studies with larger cohorts are needed to verify the usefulness of denoising-based auto-segmentation.

Compact bunker shielding assessment for 1.5 T MR-Linac.

This study evaluated the effect of the 1.5 T magnetic field of the magnetic resonance-guided linear accelerator (MR-Linac) on the radiation leakage doses penetrating the bunker radiation shielding wall. The evaluated 1.5 T MR-Linac Unity system has a bunker of the minimum recommended size. Unlike a conventional Linac, both primary beam transmission and secondary beam leakage were considered independently in the design and defined at the machine boundary away from the isocenter. Moreover, additional shielding was designed considering the numerous ducts between the treatment room and other rooms. The Linac shielding was evaluated by measuring the leakage doses at several locations. The intrinsic vibration and magnetic field were inspected at the proposed isocenter of the system. For verification, leakage doses were measured before and after applying the magnetic field. The intrinsic vibration and magnetic field readings were below the permitted limit. The leakage dose (0.05-12.2 µSv/week) also complied with internationally stipulated limits. The special shielding achieved a five-fold reduction in leakage dose. Applying the magnetic field increased the leakage dose by 0.12 to 4.56 µSv/week in several measurement points, although these values fall within experimental uncertainty. Thus, the effect of the magnetic field on the leakage dose could not be ascertained.

Mutual Information-Based Non-Local Total Variation Denoiser for Low-Dose Cone-Beam Computed Tomography.

Conventional non-local total variation (NLTV) approaches use the weight of a non-local means (NLM) filter, which degrades performance in low-dose cone-beam computed tomography (CBCT) images generated with a low milliampere-seconds (mAs) parameter value because a local patch used to determine the pixel weights comprises noisy-damaged pixels that reduce the similarity between corresponding patches. In this paper, we propose a novel type of NLTV based on a combination of mutual information (MI): MI-NLTV. It is based on a statistical measure for a similarity calculation between the corresponding bins of non-local patches vs. a reference patch. The weight is determined in terms of a statistical measure comprising the MI value between corresponding non-local patches and the reference-patch entropy. The MI-NLTV denoising process is applied to CBCT images generated by the analytical reconstruction algorithm using a ray-driven backprojector (RDB). The MI-NLTV objective function is minimized based on the steepest gradient descent optimization to augment the difference between a real structure and noise, cleaning noisy pixels without significant loss of the fine structure and details that remain in the reconstructed images. The proposed method was evaluated using patient data and actual phantom measurement data acquired with lower mAs. The results show that integrating the RDB further enhances the MI-NLTV denoising-based analytical reconstruction algorithm to achieve a higher CBCT image quality when compared with those generated by NLTV denoising-based approach, with an average of 15.97% higher contrast-to-noise ratio, 2.67% lower root mean square error, 0.12% lower spatial non-uniformity, 1.14% higher correlation, and an average of 18.11% higher detectability index. These quantitative results indicate that the incorporation of MI makes the NLTV more stable and robust than the conventional NLM filter for low-dose CBCT imaging. In addition, achieving clinically acceptable CBCT image quality despite low-mAs projection acquisition can reduce the burden on common online CBCT imaging, improving patient safety throughout the course of radiotherapy.

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.

Flexible film dosimeter for in vivo dosimetry.

PURPOSE: The aims of this study were to develop a flexible film dosimeter applicable to the irregular surface of a patient for in vivo dosimetry and to evaluate the device's dosimetric characteristics. METHODS: A flexible film dosimeter with active layers consisting of radiochromic-sensitive films and flexible silicone materials was constructed. The dose-response, sensitivity, scanning orientation dependence, energy dependence, and dose rate dependence of the flexible film dosimeter were tested. Irradiated dosimeters were scanned 24 h post-irradiation, and the region of interest was 5 mm × 5 mm. Biological stability tests ensured the safety of application of the flexible film dosimeter for patients. A preliminary clinical study with the flexible film dosimeter was implemented on four patients. RESULTS: The red channel demonstrated the highest sensitivity among all channels, and the response sensitivity of the dosimeter decreased with the applied dose, which were the same as the characteristics of GAFCHROMIC EBT3 radiochromic films. The flexible film dosimeter showed no significant energy dependence for photon beams of 6 MV, 6 MV flattening filter-free (FFF), 10 MV, and 15 MV. The flexible film dosimeter showed no substantial dose rate dependence with 6 or 6 MV FFF. In terms of biological stability, the flexible film dosimeter demonstrated no cytotoxicity, no irritation, and no skin sensitization. In the preliminary clinical study, the dose differences between the measurements with the flexible film dosimeter and calculations with the treatment planning system ranged from -0.1% to 1.2% for all patients. CONCLUSIONS: The dosimeter developed in this study is a flexible film capable of attachment to a curved skin surface. The biological test results indicate the stability of the flexible film dosimeter. The preliminary clinical study showed that the flexible film dosimeter can be successfully applied as an in vivo dosimeter.

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.

Selective toxicity of tumor treating fields to melanoma: an in vitro and in vivo study.

Tumor treating fields (TTFs) are a newly developed cancer therapy technology using an alternating electric field that may be a possible candidate for overcoming the limitations of conventional treatment methods currently used in cancer treatment. Although clinical results using TTFs appear promising, concerns regarding side effects must be clarified to demonstrate the effectiveness of this treatment method. To investigate the side effects of TTF treatment, the damage to normal cell lines and normal tissue of a mouse model was compared with the damage to tumor cells and tumors in a mouse model after TTF treatment. No serious damage was found in the normal cells and normal tissues of the mouse model, suggesting that the side effects of TTF treatment may not be serious. Our evidence based on in vitro and in vivo experiments suggests that TTF may cause selective damage to cancer cells, further demonstrating the potential of TTF as an attractive alternative to conventional cancer treatment modalities.

Rice Bran Extract Inhibits TMEM16A-Involved Activity in the Neonatal Rat Cochlea.

TMEM16A is a Ca²âº-activated Cl⁻ channel found in secretory glands, GI and respiratory tracts, and sensory organs, playing a major physiological role in fluid secretion, autonomous GI motility, and sensory transduction. In addition, overexpression of TMEM16A has been associated with cancer cell proliferation and invasion. Suppression of upregulated TMEM16A has been proposed as an effective anti-cancer strategy. While searching for a potential TMEM16A inhibitor, components of rice bran attracted our attention due to their anti-cancer potential in colon cancer cells, a type of cells known to overexpressing TMEM16A. Here, it was tested whether rice bran extract exhibits anti-TMEM16A activity. Rice bran extract was tested in the neonatal rat cochlear tissues where TMEM16A-involved spontaneous activity is generated as a part of normal development of the auditory pathway. Rice bran extract readily inhibited the TMEM16A-involved activity in the cochlear tissues and the effect was reversible upon washout. Taken together, rice bran extract appears to contain a putative TMEM16A inhibitor and the rice byproduct might serve as a source of a new anti-cancer agent.

Gold nanoparticles as a potent radiosensitizer in neutron therapy.

The purpose of this study was to investigate the potential of gold nanoparticles as radiosensitizer for use in neutron therapy against hepatocellular carcinoma. The hepatocellular carcinoma cells lines Huh7 and HepG2 were irradiated with γ and neutron radiation in the presence or absence of gold nanoparticles. Effects were evaluated by transmission electron microscopy, cell survival, cell cycle, DNA damage, migration, and invasiveness. Gold nanoparticles significantly enhanced the radiosensitivity of Huh7 and HepG2 cells to γ-rays by 1.41- and 1.16-fold, respectively, and by 1.80- and 1.35-fold to neutron radiation, which has high linear energy transfer. Accordingly, exposure to neutron radiation in the presence of gold nanoparticles induced cell cycle arrest, DNA damage, and cell death to a significantly higher extent, and suppressed cell migration and invasiveness more robustly. These effects are presumably due to the ability of gold nanoparticles to amplify the effective dose from neutron radiation more efficiently. The data suggest that gold nanoparticles may be clinically useful in combination therapy against hepatocellular carcinoma by enhancing the toxicity of radiation with high linear energy transfer.

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.

Biological effect of an alternating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation.

Alternating electric fields at an intermediate frequency (100~300 kHz), referred to as tumour-treating fields (TTF), are believed to interrupt the process of mitosis via apoptosis and to act as an inhibitor of cell proliferation. Although the existence of an antimitotic effect of TTF is widely known, the proposed apoptotic mechanism of TTF on cell function and the efficacy of TTF are controversial issues among medical experts. To resolve these controversial issues, a better understanding of the underlying molecular mechanisms of TTF on cell function and the differences between the effects of TTF alone and in combination with other treatment techniques is essential. Here, we report experimental evidence of TTF-induced apoptosis and the synergistic antimitotic effect of TTF in combination with ionizing radiation (IR). For these experiments, two human Glioblastoma multiforme (GBM) cells (U373 and U87) were treated either with TTF alone or with TTF followed by ionizing radiation (IR). Cell apoptosis, DNA damage, and mitotic abnormalities were quantified after the application of TTF, and their percentages were markedly increased when TTF was combined with IR. Our experimental results also suggested that TTF combined with IR synergistically suppressed both cell migration and invasion, based on the inhibition of MMP-9 and vimentin.

Estimation of the risk of secondary malignancy arising from whole-breast irradiation: comparison of five radiotherapy modalities, including TomoHDA.

The risk of secondary cancer from radiation treatment remains a concern for long-term breast cancer survivors, especially those treated with radiation at the age younger than 45 years. Treatment modalities optimally maximize the dose delivery to the tumor while minimizing radiation doses to neighboring organs, which can lead to secondary cancers. A new TomoTherapy treatment machine, TomoHDATM, can treat an entire breast with two static but intensity-modulated beams in a slice-by-slice fashion. This feature could reduce scattered and leakage radiation doses. We compared the plan quality and lifetime attributable risk (LAR) of a second malignancy among five treatment modalities: three-dimensional conformal radiation therapy, field-in-field forward-planned intensity-modulated radiation therapy, inverse-planned intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, and TomoDirect mode on the TomoHDA system. Ten breast cancer patients were selected for retrospective analysis. Organ equivalent doses, plan characteristics, and LARs were compared. Out-of-field organ doses were measured with radio-photoluminescence glass dosimeters. Although the IMRT plan provided overall better plan quality, including the lowest probability of pneumonitis, it caused the second highest LAR. The TomoTherapy plan provided plan quality comparable to the IMRT plan and posed the lowest total LAR to neighboring organs. Therefore, it can be a better treatment modality for younger patients who have a longer life expectancy.

Risk of secondary cancers from scattered radiation during intensity-modulated radiotherapies for hepatocellular carcinoma.

PURPOSE: To evaluate and compare the risks of secondary cancers from therapeutic doses received by patients with hepatocellular carcinoma (HCC) during intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT), and tomotherapy (TOMO). METHODS: Treatments for five patients with hepatocellular carcinoma (HCC) were planned using IMRT, VMAT, and TOMO. Based on the Biological Effects of Ionizing Radiation VII method, the excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) were evaluated from therapeutic doses, which were measured using radiophotoluminescence glass dosimeters (RPLGDs) for each organ inside a humanoid phantom. RESULTS: The average organ equivalent doses (OEDs) of 5 patients were measured as 0.23, 1.18, 0.91, 0.95, 0.97, 0.24, and 0.20 Gy for the thyroid, lung, stomach, liver, small intestine, prostate (or ovary), and rectum, respectively. From the OED measurements, LAR incidence were calculated as 83, 46, 22, 30, 2 and 6 per 10(4) person for the lung, stomach, normal liver, small intestine, prostate (or ovary), and rectum. CONCLUSIONS: We estimated the secondary cancer risks at various organs for patients with HCC who received different treatment modalities. We found that HCC treatment is associated with a high secondary cancer risk in the lung and stomach.

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.