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The linker of nucleoskeleton and cytoskeleton (LINC) complex has been implicated in various functions of the nuclear envelope, including nuclear migration, mechanotransduction and DNA repair. We previously revealed that the LINC complex component Sad1 and UNC84 domain containing 1 (SUN1) is required for sublethal-dose X-ray-enhanced cell migration and invasion. This study focused on epithelial-mesenchymal transition (EMT), which contributes to cell migration. Hence, the present study aimed to examine whether sublethal-dose X-irradiation induces EMT and whether LINC complex component SUN1 is involved in low-dose X-ray-induced EMT. This study showed that low-dose (0.5 Gy or 2 Gy) X-irradiation induced EMT in human breast cancer MDA-MB-231 cells. Additionally, X-irradiation increased the expression of SUN1. Therefore, SUN1 was depleted using siRNA. In SUN1-depleted cells, low-dose X-irradiation did not induce EMT. In addition, although the SUN1 splicing variant SUN1_916-depleted cells (containing 916 amino acids [AA] of SUN1) were induced EMT by low-dose X-irradiation like as non-transfected control cells, SUN1_888-depleted cells (which encodes 888 AA) were not induced EMT by low-dose X-irradiation. Moreover, since the Wnt/β-catenin signaling pathway regulates E-cadherin expression via the expression of the E-cadherin repressor Snail, the expression of β-catenin after X-irradiation was examined. After 24 hours of irradiation, β-catenin expression increased in non-transfected cells or SUN1_916-depleted cells, whereas β-catenin expression remained unchanged and did not increase in SUN1- or SUN1_888-depleted cells. Therefore, in this study, we found that low-dose X-irradiation induces EMT, and LINC complex component SUN1, especially SUN1_888, is required for X-ray-induced EMT via activation of the Wnt/β-catenin signaling pathway.

Pancreatic cancer is one of the most aggressive cancers and the seventh leading cause of cancer-associated death in the world. Radiation is performed as an adjuvant therapy as well as anti-cancer drugs. Because cancer stem-like cells (CSCs) are considered to be radioresistant and cause recurrence and metastasis, understanding their properties is required for the development of novel therapeutic strategies. To investigate the CSC properties of pancreatic cancer cells, we used a pancreatic CSC model, degron (++) cells, which have low proteasome activity. Degron (++) cells displayed radioresistance in comparison with control cells. Using Ribonucleic acid (RNA) sequencing, we successfully identified KRT13 as a candidate gene responsible for radioresistance. Knockdown of KRT13 sensitized the degron (++) cells to radiation. Furthermore, a database search revealed that KRT13 is upregulated in pancreatic cancer cell lines and that high expression of KRT13 is associated with poorer prognosis. These results indicate that a combination therapy of KRT13 knockdown and radiation could hold therapeutic promise in pancreatic cancer.

We conducted a nationwide survey of tomotherapy for malignant pleural mesothelioma (MPM) in Japan. Fifty-six facilities were surveyed and data on 31 patients treated curatively between 2008 and 2017 were collected from 14 facilities. Twenty patients received hemithorax irradiation after extrapleural pneumonectomy (EPP) (first group). Five patients received irradiation without EPP (second group), while six received salvage radiotherapy for local recurrence (salvage group). Among the seven patients not undergoing EPP, five (four in the second group and one in the salvage group) were treated with lung sparing pleural irradiation (LSPI) and two with irradiation to visible tumors. Two-year overall survival (OS) rates in the first and second groups were 33% and 60%, respectively (median, 13 vs 30 months, P = 0.82). In the first and second groups, 2-year local control (LC) rates were 53 and 67%, respectively (P = 0.54) and 2-year progression-free survival (PFS) rates were 16% and 60%, respectively (P = 0.07). Distant metastases occurred in 15 patients in the first group and three in the second group. In the salvage group, the median OS was 18 months. Recurrence was observed in the irradiated volume in four patients. The contralateral lung dose was higher in LSPI than in hemithorax irradiation plans (mean, 11.0 ± 2.2 vs 6.1 ± 3.1 Gy, P = 0.002). Grade 3 or 5 lung toxicity was observed in two patients receiving EPP and hemithorax irradiation, but not in those undergoing LSPI. In conclusion, outcomes of EPP and hemithorax irradiation were not satisfactory, whereas LSPI appeared promising and encouraging.

Background/Aim: The aim of this study was to evaluate the mechanical performance and the effect on dose distribution and deliverability of volumetric modulated arc therapy (VMAT) plans for prostate cancer created with the commercial knowledge-based planning (KBP) system (RapidPlan™). Materials and Methods: Three institutions, A, B, and C were enrolled in this study. Each institution established and trained a KBP model with their own cases. CT data and structures for 45 patients at institution B were utilized to validate the dose-volume parameters (D(2(%)), D(95(%),) and D(98(%)) for target, and V(50(%)), V(75(%),) and V(90(%)) for rectum and bladder), and the following mechanical performance parameters and gamma passing rates of each KBP model: leaf sequence variability (LSV), aperture area variability (AAV), total monitor unit (MU), modulation complexity score for VMAT (MCSv), MU/control point (CP), aperture area (AA)/CP, and MU×AA/CP. Results: Significant differences (p95% for all cases in each institution. Dose distribution and mechanical performance significantly differed between the three models. Conclusion: Each KBP model had different dose distributions and mechanical performance but could create an acceptable plan for deliverability regardless of mechanical performance.

Background/Aim: Dosimetric parameters in volumetric modulated arc therapy (VMAT), non-coplanar VMAT (NC-VMAT), and automated NC-VMAT (HyperArc, HA) were compared for patients with maxillary sinus carcinoma (MSC). Patients and Methods: Twenty HA plans were generated to deliver 70.4, 64, and 46 Gy for planning target volumes with high (PTV1), intermediate (PTV2), and low risk (PTV3), respectively. The VMAT and NC-VMAT plans were retrospectively generated using the same optimized parameters as those used in the HA plans. Results: For PTV1, the three treatment plans provided comparable target coverages. For PTV2, the D(95%), D(99%,) and D(min) in the HA plans (64.7±1.2, 62.7±2.1 and 54.6±6.2 Gy, respectively) were significantly higher (p

Background/Aim: This study evaluated the calculation accuracy of the stopping power ratio (SPR) using dual-energy computed tomography with fast kilovoltage switching (FKSCT) for particle therapy. Materials and Methods: A tissue characterization phantom with various reference materials was scanned to obtain single-energy computed tomography (SECT) images and generate virtual monochromatic images at 77 keV (VMI(77keV)) and 140 keV (VMI(140keV)), water density (WD) images, and effective Z (Z(eff)) images. For SECT, VMI(77keV) and VMI(140keV) lookup tables were generated to convert the measured Hounsfield value into the theoretical SPR for a normal phantom size. Subsequently, the reference materials were scanned in small and large phantoms. The SPR was calculated using the lookup tables of SECT (SPR(SECT)) images, VMI(77keV) (SPR(77keV)), and VMI(140keV) (SPR(140keV)), and it was derived from the WD and Z(eff) (SPR(WD)). Results: In the normal-sized phantom, the overall mean difference between SPR(WD) and theoretical SPR was −0.3%, and remained below 2% for most reference materials. For the large phantom, the overall mean absolute difference for SPR(140keV) (3.0%, p=0.006) and SPR(WD) (3.2%, p=0.002) for the reference materials was significantly lower than that for SPR(SECT) (5.9%). For the small phantom, a significant reduction in the mean difference in the SPR calculation was observed in SPR(77keV) (1.0%, p=0.001) and SPR(140keV) (1.1%, p=0.013) compared with SPR(SECT) (2.2%). Conclusion: VMI(140keV) generated using FKSCT significantly improves the estimation accuracy of SPR compared with SECT. Thus, FKSCT may be used to improve the dose calculation accuracy for treatment planning of particle therapy.

Radiation therapy is generally effective for treating breast cancers. However, approximately 30% of patients with breast cancer experience occasional post-treatment local and distant metastasis. Low-dose (0.5 Gy) irradiation is a risk factor that promotes the invasiveness of breast cancers. Although an inhibitor of checkpoint kinase 1 (Chk1) suppresses the growth and motility of breast cancer cell lines, no study has investigated the effects of the combined use of a Chk1 inhibitor and radiation on cancer metastasis. Here, we addressed this question by treating the human breast cancer cell line MDA-MB-231 (in vitro) and mouse mammary tumor cell line 4 T1 (in vitro and in vivo) with γ-irradiation and the Chk1 inhibitor PD407824. Low-dose γ-irradiation promoted invasiveness, which was suppressed by PD407824. Comprehensive gene expression analysis revealed that low-dose γ-irradiation upregulated the mRNA and protein levels of S100A4, the both of which were downregulated by PD407824. We conclude that PD407824 suppresses the expression of S100A4. As the result, γ-irradiation-induced cell invasiveness were inhibited.

We educate medical specialists in cancers including genomic medical specialist and pediatric/hematologic oncologists, understood the needs of patients at each stage of life from the pediatric~AYA generation to the elderly, and fostered advanced cancer medical personnel necessary for each phase of cancer treatment based on the patient's perspective. The 7 universities in the Kansai region collaborated with each other by taking advantage of their unique characteristics. We were able to establish an advanced cancer education course that understands the various needs and regional characteristics of cancer treatment and promotes team medicine. We have trained oncology surgeons, oncology/oncology pharmacotherapies, palliative medicine specialists, oncology pathologists, radiation oncologists, oncology pharmacists, oncology nurses, oncology cytologists, medical physicists, radiotherapy technicians(, from the 3rd period~)genomic medicine specialists, and pediatric hematology/oncology specialists. We were able to provide practical education that included hands-on training and practical training. We conducted educational activities in collaboration with multiple professions and multiple universities, contributing to society and the community. We promoted advanced research activities and achieved lots of research achievements. We were able to train many graduate students to become qualified cancer specialists. Graduates of the program were sent to medical institutions specializing in oncology.

We aimed to evaluate the impact of rotational setup errors on the doses received during postoperative volumetric-modulated arc therapy (VMAT) for cervical cancer. Overall, 121 cone-beam computed tomography (CBCT) sets from 20 patients were rigidly registered to reference computed tomography (CT) sets based on bony landmarks. The rotational setup errors (pitch, yaw and roll) were calculated. Then, 121 CT sets involving rotational setup errors were created, and the dose distribution in these CT sets were recalculated. The recalculated dosimetric parameters for the clinical target volume (CTV) and organs at risk (OAR) were compared to the reference values, and the correlation coefficients between the dosimetric parameter differences and rotational setup errors were calculated. Only the pitch setup error was moderately correlated with CTV coverage (r ≥ 0.40) and strongly correlated with V45 for the bladder (r ≥ 0.91) and V40 for the rectum, small bowel and bone marrow (r ≥ 0.91). The maximum dosimetric difference in a single fraction and overall fractions was −1.59% and −0.69% in D98 for the CTV, 11.72% and 5.17% in V45 for the bladder and −8.03% and −4.68% in V40 for the rectum, respectively. In conclusion, rotational setup errors only slightly impact dose coverage during postoperative cervical cancer VMAT. However, the pitch setup error occasionally affected the doses received by the bladder or the rectum in the overall fraction when the error was systematic. Thus, rotational setup errors should be corrected by adjusting six-degree-of-freedom (DOF) couches to reduce dosimetric differences in the OARs.

Purpose To evaluate the antitumor efficacy in local and distant tumors induced by local hyperthermia with CTLA-4 blockade. Methods A mouse breast cancer cell line was inoculated into both sides of the legs of mice. The mice were treated with three administrations of CTLA-4 blockade, a single application of local hyperthermia (42.5 °C for 20 min) to the tumor on one side of the leg, or the combination of the two. Tumor growth in locally heated tumors (HT tumors) and unheated distant tumors (UnHT tumors) and overall survival were evaluated. Results In the combination group, tumor volume significantly decreased for both HT and UnHT tumors compared with the tumors in the untreated and local hyperthermia monotherapy groups. Remarkable efficacy was only observed in the combination therapy group, in which 7 of 18 mice responded to HT and UnHT tumors, with significant prolonged overall survival. Conclusions Combination therapy enhanced the antitumor response not only in HT tumors but also in UnHT tumors and prolonged overall survival.

To compare the effect of a contrast-enhanced (CE) agent on volumetric-modulated arc therapy plans based on four types of images-virtual monochromatic images (VMIs) captured at 70 and 140 keV (namely VMI70 and VMI140, respectively), water density image (WDI), and virtual non-contrast image (VNC) generated using a dual-energy computed tomography (DECT) system. A tissue characterization phantom and a multi-energy phantom were scanned, and VMI70, VMI140, WDI, and VNC were retrospectively reconstructed. For each image, a lookup table (LUT) was created. For 13 patients with nasopharyngeal cancer, non-CE and CE scans were performed, and volumetric-modulated arc therapy plans were generated on the basis of non-CE VMI70. Subsequently, the doses were re-calculated using the four types of DECT images and their corresponding LUTs. The maximum differences in the physical density estimation were 21.3, 5.2, -3.9, and 0.5% for VMI70, VMI140, WDI, and VNC, respectively. Compared with VMI70, the WDI approach significantly reduced (p < 0.05) the dosimetric difference due to the CE agent for the planning target volume (PTV) (D50%), whereas the difference was significantly increased for D1%. Except for PTV (D1%), the differences were significantly lower (p < 0.05) in the treatment plans based on VMI140 and VNC than that based on VMI70. For the VNC, the mean difference was less than 0.2% for all dosimetric parameters for the PTV. For patients with NPC, treatment plans based on the VNC derived from CE scan showed the best agreement with those based on the non-CE VMI70. Ideally, the effect of CE agent on dose distribution does not appear in treatment planning procedures.

The immobilization of patients with a bite block (BB) carries the risk of interpersonal infection, particularly in the context of pandemics such as COVID-19. Here, we compared the intra-fractional patient setup error (intra-SE) with and without a BB during fractionated intracranial stereotactic irradiation (STI). Fifteen patients with brain metastases were immobilized using a BB without a medical mask, while 15 patients were immobilized without using a BB and with a medical mask. The intra-SEs in six directions (anterior–posterior (AP), superior–inferior (SI), left–right (LR), pitch, roll, and yaw) were calculated by using cone-beam computed tomography images acquired before and after the treatments. We analyzed a total of 53 and 67 treatment sessions for the with- and without-BB groups, respectively. A comparable absolute mean translational and rotational intra-SE was observed (P > 0.05) in the AP (0.19 vs 0.23 mm with- and without-BB, respectively), SI (0.30 vs 0.29 mm), LR (0.20 vs 0.29 mm), pitch (0.18 vs 0.27°), roll (0.23 vs 0.23°) and yaw (0.27 vs 22°) directions. The resultant planning target volume (PTV) margin to compensate for intra-SE was

Background/aim This study aimed to investigate the potential differences between multi-institutional measurements and treatment planning system (TPS) calculation modeled by representative beam data for patient-specific quality assurance (QA), including multi-leaf collimator (MLC) parameters. Materials and methods Eleven TrueBeam from nine institutions were used in this study. Volumetric arc therapy (VMAT) plan for verification was created using Eclipse. The point dose of the CC13 ionization chamber and the dose distribution of the GAFCHROMIC EBT3 film were measured and analyzed. Results Point dose differences in patient-specific QA provided a mean±standard deviation of 1.0%±0.6%. Mean gamma pass rates of dose distribution were in excess of 99% and 96% for 3%/2 mm and 2%/2 mm gamma criteria, respectively. Conclusion There was good agreement between measurements and calculations, indicating the small influence of complex VMAT in the underlying processes. Therefore, implementation of the same MLC parameters on TPS among different institutions with the same planning policy should be considered to ensure consistency and efficiency in radiation treatment processes.

Background/aim The Purpose of this study was to develop a Monte Carlo (MC) model for the Agility multileaf collimator (MLC) mounted and to validate its accuracy. Materials and methods To describe the Agility MLC in the BEAMnrc MC code, an existing component module code was modified to include its characteristics. The leaf characterization of the MC model was validated by comparing the calculated interleaf transmission and tongue-and-groove effect with EBT2 film and diode measurements and IMRT and VMAT calculations with film measurements. Results Agreement between mean calculated and measured leaf transmissions was within 0.1%. The discrepancy between MC calculation and measurement in a static irregular field was less than 2%/2 mm. Gamma analysis of the comparison of MC and EBT2 film measurements in IMRT and VMAT fields yielded pass rates of 99.1% and 99.5% with 3%/3 mm criteria, respectively. Conclusion Our findings demonstrate the accuracy of the MC model using an adapted BEAMnrc component module for the Agility MLC.

This study introduced an A-mode portable ultrasound bladder scanner, the Lilium® α-200 (here after Lilium; Lilium Otsuka, Kanagawa, Japan), for the treatment of prostate cancer patients with hypofractionated volumetric modulated arc therapy to improve the reproducibility of bladder volume (BV).Thirty patients were advised to maintain full BV prior to computed tomography (CT) simulation and daily treatment. Among these, the BV of 15 patients was measured using Lilium until a BV of 80% in the simulation was achieved (with the Lilium group). Daily cone-beam CT (CBCT) was performed for treatment. The correlation between BV measured by CBCT and Lilium was assessed. The differences in the BV and dosimetric parameters of the bladder in the CBCT versus planning CT were compared between the groups with and without Lilium.There was a significantly strong relationship (r = 0.796, p 0.05) between the BVs measured using CBCT and Lilium. The relative BV ratios to simulation CT 0.5 and 2 were observed in 10.3% and 12.7%, respectively, of treatment sessions without Lilium group, while these ratios were 1% and 2.8%, respectively, in the Lilium group. The mean absolute difference in the range of VThe use of the A-mode portable ultrasound bladder scanner significantly improved the reproducibility of the BV, resulting in few variations in the dosimetric parameters for the bladder.

Objective: We evaluated the radiobiological effect of the irradiation time with the interruption time of stereotactic radiosurgery (SRS) using CyberKnife® (CK) systemfor brain metastases. Methods: We used the DICOM data and irradiation log file of the 10 patients with brain metastases from non–small-cell lung cancer (NSCLC) who underwent brain SRS. We defined the treatment time as the sum of the dose–delivery time and the interruption time during irradiations, and we used a microdosimetric kinetic model (MKM) to evaluate the radiobiological effects of the treatment time. The biological parameters, i.e. α0, β0, and the DNA repair constant rate (a + c), were acquired from NCI-H460 cell for the MKM. We calculated the radiobiological dose for the gross tumor volume (GTVbio) to evaluate the treatment time’s effect compared with no treatment time as a reference. The D95 (%) and the Radiation Therapy Oncology Group conformity index (RCI) and Paddick conformity index (PCI) were calculated as dosimetric indices. We used several DNA repair constant rates (a + c) (0.46, 1.0, and 2.0) to assess the radiobiological effect by varying the DNA repair date (a + c) values. Results: The mean values of D95 (%), RCI, and PCI for GTVbio were 98.8%, 0.90, and 0.80, respectively, and decreased with increasing treatment time. The mean values of D95 (%), RCI, and PCI of GTVbio at 2.0 (a+c) value were 94.9%, 0.71, and 0.49, respectively. Conclusion: The radiobiological effect of the treatment time on tumors was accurately evaluated with brain SRS using CK. Advances in knowledge: There has been no published investigation of the radiobiological impact of the longer treatment time with multiple interruptions of SRS using a CK on the target dose distribution in a comparison with the use of a linac. Radiobiological dose assessment that takes into account treatment time in the physical dose in this study may allow more accurate dose assessment in SRS for metastatic brain tumors using CK.

To compare the intrafractional motion error (IME) during stereotactic irradiation (STI) in patients with brain metastases immobilized using open- (Encompass) and full-face (DSPS) clamshell-style immobilization devices.Encompass (38 patients) and DSPS (38 patients) were used for patient immobilization, and HyperArc plans with three to four non-coplanar beams were generated to deliver 25 to 35 Gy in three to five fractions. Cone-beam computed tomography (CBCT) was performed on patients before and after the treatment. Moreover, the difference in patient position between the two CBCT images was considered as the IME. The margins to compensate for IME were calculated using the van Herk margin formula.For Encompass, the mean values of IME in the translational setup were 0.1, 0.2, and 0.0 mm in the anterior-posterior, superior-inferior, and left-right directions, respectively, and the mean values of IME about rotational axes were -0.1, 0.0, and 0.0° for the Pitch, Roll, and Yaw rotations, respectively. For DSPS, the mean values of IME in the translational setup were 0.2, 0.2, and 0.0 mm in the anterior-posterior, superior-inferior, and left-right directions, respectively, and the mean values of IME about rotational axes were -0.1, -0.1, and 0.0° for the Pitch, Roll, and Yaw rotations, respectively. No statistically significant difference was observed between the IME of the two immobilization systems except in the anterior-posterior direction (p = 0.02). Moreover, no statistically significant correlation was observed between three-dimensional IME and treatment time. The margin compensation for IME was less than 1 mm for both immobilization devices.The IME during STI using open- and full-face clamshell-style immobilization devices is approximately equal considering the adequate accuracy in patient positioning.

Accurate clinical target volume (CTV) delineation is important for head and neck intensity-modulated radiation therapy. However, delineation is time-consuming and susceptible to interobserver variability (IOV). Based on a manual contouring process commonly used in clinical practice, we developed a deep learning (DL)-based method to delineate a low-risk CTV with computed tomography (CT) and gross tumor volume (GTV) input and compared it with a CT-only input. A total of 310 patients with oropharynx cancer were randomly divided into the training set (250) and test set (60). The low-risk CTV and primary GTV contours were used to generate label data for the input and ground truth. A 3D U-Net with a two-channel input of CT and GTV (U-Net

Recent advancements of spatial audio technologies to enhance human’s emotional and immersive experiences are gathering attention. Many studies are clarifying the neural mechanisms of acoustic spatial perception; however, they are limited to the evaluation of mechanisms using basic sound stimuli. Therefore, it remains challenging to evaluate the experience of actual music contents and to verify the effects of higher-order neurophysiological responses including a sense of immersive and realistic experience. To investigate the effects of spatial audio experience, we verified the psychophysiological responses of immersive spatial audio experience using sound field synthesis (SFS) technology. Specifically, we evaluated alpha power as the central nervous system activity, heart rate/heart rate variability and skin conductance as the autonomic nervous system activity during an acoustic experience of an actual music content by comparing stereo and SFS conditions. As a result, statistically significant differences (p < 0.05) were detected in the changes in alpha wave power, high frequency wave power of heart rate variability (HF), and skin conductance level (SCL) among the conditions. The results of the SFS condition showed enhanced the changes in alpha power in the frontal and parietal regions, suggesting enhancement of emotional experience. The results of the SFS condition also suggested that close objects are grouped and perceived on the basis of the spatial proximity of sounds in the presence of multiple sound sources. It is demonstrating that the potential use of SFS technology can enhance emotional and immersive experiences by spatial acoustic expression.

Purpose To evaluate the utility of the use of iterative cone-beam computed tomography (CBCT) for machine log file-based dose verification during volumetric modulated arc therapy (VMAT) for prostate cancer patients. Methods All CBCT acquisition data were used to reconstruct images with the Feldkamp-Davis-Kress algorithm (FDK-CBCT) and the novel iterative algorithm (iCBCT). The Hounsfield unit (HU)-electron density curves for CBCT images were created using the Advanced Electron Density Phantom. The I'mRT and anthropomorphic phantoms were irradiated with VMAT after CBCT registration. Subsequently, fourteen prostate cancer patients received VMAT after CBCT registration. Machine log files and both CBCT images were exported to the PerFRACTION software, and a 3D patient dose was reconstructed. Mean dose for planning target volume (PTV), the bladder, and rectum and the 3D gamma analysis were evaluated. Results For the phantom studies, the variation of HU values was observed at the central position surrounding the bones in FDK-CBCT. There were almost no changes in the difference of doses at the isocenter between measurement and reconstructed dose for planning CT (pCT), FDK-CBCT, and iCBCT. Mean dose differences of PTV, rectum, and bladder between iCBCT and pCT were approximately 2% lower than those between FDK-CBCT and pCT. For the clinical study, average gamma analysis for 2%/2 mm was 98.22% ± 1.07 and 98.81% ± 1.25% in FDK-CBCT and iCBCT, respectively. Conclusions A similar machine log file-based dose verification accuracy is obtained for FDK-CBCT and iCBCT during VMAT for prostate cancer patients.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 836), telecobalt (n = 3), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 24), and 192Ir RALS (n = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Purpose In stereotactic radiosurgery (SRS) with single‐isocentric treatments for brain metastases, rotational setup errors may cause considerable dosimetric effects. We assessed the dosimetric effects on HyperArc plans for single and multiple metastases. Methods For 29 patients (1–8 brain metastases), HyperArc plans with a prescription dose of 20–24 Gy for a dose that covers 95% (D95%) of the planning target volume (PTV) were retrospectively generated (Ref‐plan). Subsequently, the computed tomography (CT) used for the Ref‐plan and cone‐beam CT acquired during treatments (Rot‐CT) were registered. The HyperArc plans involving rotational setup errors (Rot‐plan) were generated by re‐calculating doses based on the Rot‐CT. The dosimetric parameters between the two plans were compared. Results The dosimetric parameters [D99%, D95%, D1%, homogeneity index, and conformity index (CI)] for the single‐metastasis cases were comparable (P > 0.05), whereas the D95% for each PTV of the Rot‐plan decreased 10.8% on average, and the CI of the Rot‐plan was also significantly lower than that of the Ref‐plan (Ref‐plan vs Rot‐plan, 0.93 ± 0.02 vs 0.75 ± 0.14, P

Background/aim Ro 90-7501 has been reported as an inhibitor of the amyloid β42 fibril assembly that is associated with Alzheimer's disease. The present study aimed to elucidate the radiosensitizing effects of Ro 90-7501 and focused on ATM signaling after irradiation. Materials and methods Clonogenic survival, apoptosis, and cell-cycle assays as well as western blotting were performed in HeLa cells treated with irradiation and Ro 90-7501. Tumor growth delay assay was also performed using BALB/c-nu mice. Results The combination of irradiation with Ro 90-7501 showed significant radiosensitizing effects in clonogenic survival and tumor growth delay assays. Ro 90-7501 significantly increased apoptosis and impaired cell cycle after irradiation. Western blotting showed that Ro 90-7501 suppressed the phosphorylation of ATM and its downstream proteins, such as H2AX, Chk1, and Chk2, after irradiation. Conclusion Ro 90-7501 inhibits DNA damage response by inhibiting ATM and has significant radiosensitizing effects on cervical cancer cells.

Purpose Though virtual monochromatic images (VMIs) at low energy levels can improve image quality, the measured Hounsfield unit (HU) values can be inaccurate. We assessed the dosimetric error due to inaccurate HU estimation in volumetric modulated arc therapy (VMAT) planning. Methods Based on the VMIs at 50 keV (VMI50keV), 77 keV (VMI77keV) and single-energy CT (SECT) image for a phantom with different sizes, lookup tables (LUTL and LUTS) were created. Using an anthropomorphic phantom (head and spine regions), VMAT plans were generated based on VMI50keV, VMI77keV and SECT using the corresponding LUTL, and then, the doses were re-calculated using LUTS. For clinical cases, 30 VMAT plans (prostate, brain, and spine cases) were generated based on VMI50keV and VMI77keV. Results In the anthropomorphic phantom study, the difference in the dosimetric parameters for planning target volume (PTV) in the VMAT plan based on the VMI77keV was smallest (within 0.1 Gy) among three types of treatment planning approach. In clinical cases, in general, the differences of the 3-dimensional gamma passing rate and dosimetric parameters in the treatment plans based on the VMI50keV were larger than those in the VMI77keV. Especially for brain cases, the difference for PTV was more prominent when AXB was used (the maximum difference was 0.5 Gy) than AAA. Conclusions The dosimetric error due to the inaccurate HU estimation was larger in the VMIs at low energy levels. This may be clinically insignificant, but should be avoided in the VMAT treatment planning.

Purpose Assess the accuracy for quantitative measurements of electron density relative to water (ρe/ρe,w), effective atomic number (Zeff) and stopping power ratio relative to water (SPRw) using a dual-layer computed tomography (DLCT) system. Methods and Materials A tissue characterization phantom was scanned using DLCT with varying scanning parameters (i.e., tube voltage, rotation time, CTDIvol, and scanning mode) and different reference materials. Then, electron density ρe/ρe,w and atomic number Zeff images were reconstructed, and their values were determined for each reference materials. Based on these two values, SPRw was calculated. Finally, the percent error (PE) against the theoretical values was calculated for reference materials. Results Significant linear relationships (p 0.85). Conclusions DLCT provides a reasonable accuracy in the measurements of ρe/ρe,w, Zeff and SPRw, and could enhance radiotherapy treatment planning and the subsequent outcomes.

BACKGROUND/AIM To assess the impact of the width of multileaf collimator (MLC) on dose distributions on HyperArc fractionated stereotactic irradiation for multiple (5-10) brain metastases. PATIENTS AND METHODS Twenty-one HyperArc (HA) plans were generated using the high definition (HD) MLC (2.5 mm) to deliver 30-35 Gy in 3-5 fractions (HA-HD). The HyperArc plans using Millennium (ML) MLC (5 mm) were retrospectively generated (HA-ML) using the same planning parameters with HA-HD. Dosimetric parameters between the planning target volume (PTV) and organs at risk (OARs) were compared. RESULTS The conformity index was significantly higher (p

Pancreatic cancer is an extremely treatment-resistant neoplasm to chemotherapy and immunotherapy. The combination of photon beam irradiation and anti-CTLA-4 antibody (C4) for the anti-tumor effect enhancement at local and distant tumors (abscopal tumors) was investigated using the pancreatic ductal adenocarcinoma (PDAC) mouse model. Pan02 cells were bilaterally inoculated to both legs of C57BL/6 mice. High dose photon beams in a hypofractionation or a single fraction were delivered to the tumors on one leg. Monotherapy with C4 via i.p. was not effective for PDAC. The high dose irradiation to the local tumors produced significant shrinkage of irradiated tumors but did not induce the abscopal responses. In contrast, the combination therapy of high dose photon beam irradiation in both hypofractionation and a single fraction with C4 enhanced the anti-tumor effect for abscopal tumors with significantly prolonged overall survival. The flow cytometric analysis revealed that the combination therapy dramatically decreased the regulatory T cell (Treg) proportion while increasing the cytotoxic T lymphocytes in both local and abscopal tumors. These results suggest that high dose photon beam irradiation plays an important role in C4 therapy to enhance the abscopal response with immune microenvironment changes in PDAC, regardless of the fractionation in radiation therapy.

To construct a deep convolutional neural network that generates virtual monochromatic images (VMIs) from single-energy computed tomography (SECT) images for improved pancreatic cancer imaging quality.Fifty patients with pancreatic cancer underwent a dual-energy CT simulation and VMIs at 77 and 60 keV were reconstructed. A 2D deep densely connected convolutional neural network was modeled to learn the relationship between the VMIs at 77 (input) and 60 keV (ground-truth). Subsequently, VMIs were generated for 20 patients from SECT images using the trained deep learning model.The contrast-to-noise ratio was significantly improved (p 0.001) in the generated VMIs (4.1 ± 1.8) compared to the SECT images (2.8 ± 1.1). The mean overall image quality (4.1 ± 0.6) and tumor enhancement (3.6 ± 0.6) in the generated VMIs assessed on a five-point scale were significantly higher (p 0.001) than that in the SECT images (3.2 ± 0.4 and 2.8 ± 0.4 for overall image quality and tumor enhancement, respectively).The quality of the SECT image was significantly improved both objectively and subjectively using the proposed deep learning model for pancreatic tumors in radiotherapy.

Background Total scalp irradiation presents technical and dosimetric challenges. While reports suggest that HyperArc, a new stereotactic radiosurgery planning technique applied to non-coplanar volumetric-modulated arc therapy (VMAT) technique, is associated with high conformity and rapid dose fall-off, the performance of HyperArc for total scalp irradiation has not been explored. The current study aimed to compare the dosimetric performance of HyperArc plans with those of non-coplanar VMAT plans in angiosarcoma of the scalp. Methods Ten patients with angiosarcoma of the scalp were included in this study. The performance of three different plans administered using TrueBeam Edge were compared: non-coplanar VMAT using flattening filter (FF) beams (VMAT-FF), HyperArc using FF beams (HyperArc-FF), and HyperArc using flattening filter free (FFF) beams (HyperArc-FFF). The dose distribution, dosimetric parameters, and dosimetric accuracy for each of these plans were evaluated. Results The three plans showed no statistically significant differences in target volume coverage, conformity, and homogeneity. The HyperArc-FF and HyperArc-FFF plans provided significantly lower mean brain doses (12.63 ± 3.31 Gy and 12.71 ± 3.40 Gy) than did the VMAT-FF plans (17.11 ± 5.25 Gy). There were almost no differences in sparing the organs at risk between the HyperArc-FF and HyperArc-FFF plans. The HyperArc-FF and HyperArc-FFF plans provided a shorter beam-on time than did the VMAT-FF plan. The 3%/2 mm gamma test pass rates were above 95% for all three plans. Conclusions Our results suggest that the HyperArc plan can be potentially used for radiation therapy of target regions with large and complicated shapes, such as the scalp, and that there are no advantages of using FFF beams.

Background: The aim of the study was to evaluate analysis criteria for the identification of the presence of rectal gas during volumetric modulated arc therapy (VMAT) for prostate cancer patients by using electronic portal imaging device (EPID)-based in vivo dosimetry (IVD). Materials and methods: All measurements were performed by determining the cumulative EPID images in an integrated acquisition mode and analyzed using PerFRACTION commercial software. Systematic setup errors were simulated by moving the anthropomorphic phantom in each translational and rotational direction. The inhomogeneity regions were also simulated by the I’mRT phantom attached to the Quasar phantom. The presence of small and large air cavities (12 and 48 cm 3 ) was controlled by moving the Quasar phantom in several timings during VMAT. Sixteen prostate cancer patients received EPID-based IVD during VMAT. Results: In the phantom study, no systematic setup error was detected in the range that can happen in clinical ( < 5-mm and < 3 degree). The pass rate of 2% dose difference (DD2%) in small and large air cavities was 98.74% and 79.05%, respectively, in the appearance of the air cavity after irradiation three quarter times. In the clinical study, some fractions caused a sharp decline in the DD2% pass rate. The proportion for DD2% < 90% was 13.4% of all fractions. Rectal gas was confirmed in 11.0% of fractions by acquiring kilo-voltage X-ray images after the treatment. Conclusions: Our results suggest that analysis criteria of 2% dose difference in EPID-based IVD was a suitable method for identification of rectal gas during VMAT for prostate cancer patients.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and overcome any existing limitations. From March 2011 to June 2013, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2010. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 251 000, respectively. Additionally, the estimated cancer incidence was 805 236 cases, with ~26.2% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 829), telecobalt (n = 9), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 28), and 192Ir RALS (n = 131). The LINAC system used dual-energy functions in 586 units, three-dimensional conformal radiotherapy functions in 663, and intensity-modulated radiotherapy (IMRT) functions in 337. There were 564 JASTRO-certified radiation oncologists, 959.2 full-time equivalent (FTE) radiation oncologists, 1841.3 FTE radiotherapy technologists, 131.3 FTE medical physicists, 121.5 FTE radiotherapy quality managers, and 649.6 FTE nurses. The frequency of IMRT use significantly increased during this year. To conclude, although there was a shortage of personnel in 2010, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation‐enhanced cell migration and invasion. A sublethal dose of X‐ray radiation promoted human breast cancer MDA‐MB‐231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose‐dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X‐ray‐enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X‐ray‐enhanced migration and invasion. In addition, the results suggested that X‐ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon‐enhanced cell migration and invasion.