Variation in Hounsfield unit calculated using dual-energy computed tomography: comparison of dual-layer, dual-source, and fast kilovoltage switching technique.

The purpose of the study is to investigate the variation in Hounsfield unit (HU) values calculated using dual-energy computed tomography (DECT) scanners. A tissue characterization phantom inserting 16 reference materials were scanned three times using DECT scanners [dual-layer CT (DLCT), dual-source CT (DSCT), and fast kilovoltage switching CT (FKSCT)] changing scanning conditions. The single-energy CT images (120 or 140 kVp), and virtual monochromatic images at 70 keV (VMI70) and 140 keV (VMI140) were reconstructed, and the HU values of each reference material were measured. The difference in HU values was larger when the phantom was scanned using the half dose with wrapping with rubber (strong beam-hardening effect) compared with the full dose without the rubber (reference condition), and the difference was larger as the electron density increased. For SECT, the difference in HU values against the reference condition measured by the DSCT (3.2 ± 5.0 HU) was significantly smaller (p < 0.05) than that using DLCT with 120 kVp (22.4 ± 23.8 HU), DLCT with 140 kVp (11.4 ± 12.8 HU), and FKSCT (13.4 ± 14.3 HU). The respective difference in HU values in the VMI70 and VMI140 measured using the DSCT (10.8 ± 17.1 and 3.5 ± 4.1 HU) and FKSCT (11.5 ± 21.8 and 5.5 ± 10.4 HU) were significantly smaller than those measured using the DLCT120 (23.1 ± 27.5 and 12.4 ± 9.4 HU) and DLCT140 (22.3 ± 28.6 and 13.1 ± 11.4 HU). The HU values and the susceptibility to beam-hardening effects varied widely depending on the DECT scanners.

Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams.

The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.

Long-term geometric quality assurance of radiation focal point and cone-beam computed tomography for Gamma Knife radiosurgery system.

To investigate the geometric accuracy of the radiation focal point (RFP) and cone-beam computed tomography (CBCT) over long-term periods for the ICON Leksell Gamma Knife radiosurgery system. This phantom study utilized the ICON quality assurance tool plus, and the phantom was manually set on the patient position system before the implementation of treatment for patients. The deviation of the RFP position from the unit center point (UCP) and the positions of the four ball bearings (BBs) in the CBCT from the reference position were automatically analyzed. During 544 days, a total of 269 analyses were performed on different days. The mean ± standard deviation (SD) of the deviation between measured RFP and UCP was 0.01 ± 0.03, 0.01 ± 0.03, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively. The deviations with offset values after the cobalt-60 source replacement (0.00 ± 0.03, -0.01 ± 0.01, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively) were significantly (p = 0.001) smaller than those before the replacement (0.02 ± 0.03, 0.02 ± 0.01, and -0.02 ± 0.01 mm in the X, Y, and Z directions, respectively). The overall mean ± SD of four BBs was -0.03 ± 0.03, -0.01 ± 0.05, and 0.01 ± 0.03 mm in the X, Y, and Z directions, respectively. Geometric positional accuracy was ensured to be within 0.1 mm on most days over a long-term period of more than 500 days.

Correlation Between Dosimetric Parameters and Local Control in Definitive Radiotherapy for Head and Neck Cancers.

BACKGROUND/AIM: Radiotherapy (RT) outcomes are generally reported based on stage, patient background, and concomitant chemotherapy. This study aimed to investigate the effects of the prescribed dose to gross tumor volume (GTV) and the calculation algorithm on local control in definitive RT for head and neck (H&N) cancers using follow-up images after RT. PATIENTS AND METHODS: This study included 154 patients with H&N cancers treated by Volumetric Modulated Arc Therapy at the Kobe City Medical Center General Hospital. Patients were classified into those receiving definitive RT (70 Gy of irradiation) and those not receiving it. Follow-up images were used to categorize the patients into the responders and non-responders groups. In the non-responders group, follow-up images were imported into the treatment planning system, and the contours of the residual or recurrent areas (local failure) were extracted and fused with computed tomography-simulated images for treatment planning. Dose evaluation parameters included maximum dose, dose administered to 1% of the volume, dose administered to 50% of the volume, dose administered to 99% of the volume (D99%), and minimum dose (Dmin) administered to the GTV. The doses to the GTV were compared between responders and non-responders. RESULTS: D99% exhibited significant differences between local failure and responders and between local failure and non-responders. Dmin showed significant differences between responders and non-responders and between responders and local failure. CONCLUSION: This study emphasizes the importance of verifying dose distribution in all slices of treatment planning, highlighting the need for precise assessment of the dose to the GTV in head and neck cancers.

Circulating Plasma Exosomal PD-L1 Predicts Prognosis of Head and Neck Squamous Cell Carcinoma After Radiation Therapy.

Purpose: Radiation therapy is widely used to treat head and neck squamous cell carcinoma (HNSCC). This study evaluated the association between circulating plasma programmed death-ligand 1 (PD-L1) and the outcomes of patients with HNSCC after radiation therapy. Methods and Materials: In this retrospective observational study, plasma samples of 76 patients with HNSCC who underwent radiation therapy from June 2019 to August 2021 were analyzed. These plasma samples were obtained before radiation therapy. The median follow-up was 32.5 months. Total and exosomal PD-L1 was measured by enzyme-linked immunosorbent assay and retrospectively analyzed for association with overall survival (OS), progression-free survival (PFS), and local control (LC). Prognostic factors among patients' characteristics and circulating PD-L1 in plasma were evaluated by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses. Results: The median concentration of total PD-L1 in plasma was 115.1 pg/mL (95% CI, 114.7-137.9 pg/mL), and the median concentration of exosomal PD-L1 was 2.8 pg/mL (95% CI, 6.0-13.0 pg/mL). Univariate and multivariate analyses showed exosomal PD-L1 as a prognostic factor for PFS and LC. Patients with high exosomal PD-L1 in plasma had poor PFS and LC compared with those with low exosomal PD-L1, indicating that 1-year PFS was 79.2% versus 33.3% (P < .001) and 1-year LC was 87.3% versus 50.0% (P < .001) in patients with high and low exosomal PD-L1, respectively. However, exosomal PD-L1 in plasma had no significant effect on OS. Total PD-L1 in plasma did not correlate with PFS, LC, and OS. Conclusions: The pretreatment circulating exosomal PD-L1 in plasma of patients with HNSCC was a prognostic factor after radiation therapy.

Relationship between hydrogel spacer distribution and dosimetric parameters in linear-accelerator-based stereotactic body radiotherapy for prostate cancer.

PURPOSE: To explore the potential of quantitative parameters of the hydrogel spacer distribution as predictors for separating the rectum from the planning target volume (PTV) in linear-accelerator-based stereotactic body radiotherapy (SBRT) for prostate cancer. METHODS: Fifty-five patients underwent insertion of a hydrogel spacer and were divided into groups 1 and 2 of the PTV separated from and overlapping with the rectum, respectively. Prescribed doses of 36.25-45 Gy in five fractions were delivered to the PTV. The spacer cover ratio (SCR) and hydrogel-implant quality score (HIQS) were calculated. RESULTS: Dosimetric and quantitative parameters of the hydrogel spacer distribution were compared between the two groups. For PTV, D99% in group 1 (n = 29) was significantly higher than that in group 2 (n = 26), and Dmax , D0.03cc , D1cc , and D10% for the rectum were significantly lower in group 1 than in group 2. The SCR for prostate (89.5 ± 12.2%) in group 1 was significantly higher (p < 0.05) than that in group 2 (74.7 ± 10.3%). In contrast, the HIQS values did not show a significant difference between the groups. An area under the curve of 0.822 (95% confidence interval, 0.708-0.936) for the SCR was obtained with a cutoff of 93.6%, sensitivity of 62.1%, and specificity of 100%. CONCLUSIONS: The SCR seems promising to predict the separation of the rectum from the PTV in linear-accelerator-based SBRT for prostate cancer.

The effects of distance between the imaging isocenter and brain center on the image quality of cone-beam computed tomography for brain stereotactic irradiation.

In linear accelerator-based stereotactic irradiation (STI) for brain metastasis, cone-beam computed tomography (CBCT) image quality is essential for ensuring precise patient setup and tumor localization. However, CBCT images may be degraded by the deviation of the CBCT isocenter from the brain center. This study aims to investigate the effects of the distance from the brain center to the CBCT isocenter (DBI) on the image quality in STI. An anthropomorphic phantom was scanned with varying DBI in right, anterior, superior, and inferior directions. Thirty patients undergoing STI were prospectively recruited. Objective metrics, utilizing regions of interest included contrast-to-noise ratio (CNR) at the centrum semiovale, lateral ventricle, and basal ganglia levels, gray and white matter noise at the basal ganglia level, artifact index (AI), and nonuniformity (NU). Two radiation oncologists assessed subjective metrics. In this phantom study, objective measures indicated a degradation in image quality for non-zero DBI. In this patient study, there were significant correlations between the CNR at the centrum semiovale and lateral ventricle levels (rs = - 0.79 and - 0.77, respectively), gray matter noise (rs = 0.52), AI (rs = 0.72), and NU (rs = 0.91) and DBI. However, no significant correlations were observed between the CNR at the basal ganglia level, white matter noise, and subjective metrics and DBI (rs < ± 0.3). Our results demonstrate the effects of DBI on contrast, noise, artifacts in the posterior fossa, and uniformity of CBCT images in STI. Aligning the CBCT isocenter with the brain center can aid in improving image quality.

Impact of magnetic resonance imaging-related geometric distortion of dose distribution in fractionated stereotactic radiotherapy in patients with brain metastases.

PURPOSE: The geometric distortion related to magnetic resonance (MR) imaging in a diagnostic radiology (MRDR) and radiotherapy (MRRT) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated. MATERIALS AND METHODS: An anthropomorphic skull phantom was scanned using a 1.5­T MR scanner, and the magnitude of MR distortion was calculated with (MRDR-DC and MRRT-DC) and without (MRDR-nDC and MRRT-nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53 patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MRRT-DC and MRRT-nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HADC and HAnDC). RESULTS: The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MRDR-DC, MRDR-nDC, MRRT-DC, and MRRT-nDC, respectively). The dose to the 98% of the GTV volume (D98%) decreased as the distance from the MIC increased. In the HADC plans, the relative dose difference of D98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HAnDC plans. CONCLUSION: Use of a distortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC.

Irradiated Cell-derived Exosomes Enhance Cell Proliferation and Radioresistance via the MAPK/Erk Pathway.

BACKGROUND/AIM: Radiation therapy is pivotal in cancer treatment; however, its efficacy is limited by challenges such as tumor recurrence. This study delves into the role of exosomes, which are molecular cargo-bearing vesicles, in influencing cell proliferation, radioresistance, and consequent post-irradiation tumor recurrence. Given the significance of exosomes from irradiated malignancies in diagnostics and therapy, it is vital to delineate their functional dynamics, especially in breast and cervical cancer cell lines, where the impact of irradiation on exosome behavior remains enigmatic. MATERIALS AND METHODS: Using MDA-MB-231 and HeLa cell lines, exosomes were isolated from the culture supernatant via ultracentrifugation. The bicinchoninic acid assay was used to measure exosome quantities in irradiated and non-irradiated cells. Radiosensitivity was assessed using colony formation assays, while the role of the MAPK/Erk signaling pathway in recipient cell proliferation and radioresistance was probed using western blotting. RESULTS: Irradiated cells, in both MDA-MB-231 and HeLa lines, produced significantly more exosomes than their non-irradiated counterparts. Co-culturing irradiated cells with exosomes led to increased cell survival post-irradiation and enhanced cell proliferation in both cell lines. Western blotting indicated elevated p-Erk expression in such cells, underscoring the influence of the MAPK/Erk pathway in radioresistance and proliferation. CONCLUSION: The study establishes a potential nexus between exosome secretion and tumor resurgence following radiotherapy. The spotlight falls on the MAPK/ERK signaling conduit as a key influencer. This new knowledge provides an innovative strategy for counteracting cancer recurrence after radiotherapy, emphasizing the importance of understanding the multifaceted roles of exosomes in this context.

Dual-energy computed tomography-based iodine concentration as a predictor of histopathological response to preoperative chemoradiotherapy for pancreatic cancer.

To explore predictors of the histopathological response to preoperative chemoradiotherapy (CRT) in patients with pancreatic cancer (PC) using dual-energy computed tomography-reconstructed images. This retrospective study divided 40 patients who had undergone preoperative CRT (50-60 Gy in 25 fractions) followed by surgical resection into two groups: the response group (Grades II, III and IV, evaluated from surgical specimens) and the nonresponse group (Grades Ia and Ib). The computed tomography number [in Hounsfield units (HUs)] and iodine concentration (IC) were measured at the locations of the aorta, PC and pancreatic parenchyma (PP) in the contrast-enhanced 4D dual-energy computed tomography images. Logistic regression analysis was performed to identify predictors of histopathological response. Univariate analysis did not reveal a significant relation between any parameter and patient characteristics or dosimetric parameters of the treatment plan. The HU and IC values in PP and the differences in HU and IC between the PP and PC (ΔHU and ΔIC, respectively) were significant predictors for distinguishing the response (n = 24) and nonresponse (n = 16) groups (P < 0.05). The IC in PP and ΔIC had a higher area under curve values [0.797 (95% confidence interval, 0.659-0.935) and 0.789 (0.650-0.928), respectively] than HU in PP and ΔHU [0.734 (0.580-0.889) and 0.721 (0.562-0.881), respectively]. The IC value could potentially be used for predicting the histopathological response in patients who have undergone preoperative CRT.

Autonomic function measurements for evaluating fatigue and quality of life in patients with breast cancer undergoing radiation therapy: a prospective longitudinal study.

BACKGROUND: Fatigue during radiation therapy in women with breast cancer can decrease quality of life (QOL), yet it is often underestimated and needs to be evaluated objectively. This longitudinal study aimed to evaluate fatigue and QOL of women with breast cancer undergoing radiotherapy with a simple autonomic function measurement. METHODS: Women with breast cancer who underwent postoperative radiotherapy in eight cancer care hospitals in Chubu and Kinki regions in Japan were recruited between October 2021 and June 2022. The women underwent a self-administered questionnaire that included the Cancer Fatigue Scale (CFS) and the Short Form-8 Health Survey (SF-8) and an autonomic nervous function measurement using a simple, non-invasive device before (T0, baseline), mid (T1), and at the end (T2) of treatment. RESULTS: The 57 women showed similar trends, with CFS scores and log LF/HF ratio being the highest at T0 and significantly decreasing at T1 (both p < 0.05). The log LF/HF trends differed between those with high and low baseline log LF/HF values. Women with mental component summary (MCS) score improvement (T0 to T2) had the highest log LF/HF ratio at T0 and had significantly lower log LF/HF values at T1 and T2 than at T0 (p < 0.01 and p < 0.05, respectively). The change of (⊿) MCS from T0 to T1 was negatively correlated with ⊿log LF/HF from T0 to T1 (r = - 0.36, p < 0.01). CONCLUSIONS: Measurement of autonomic nerve function with a simple device is useful for objective fatigue assessment during radiotherapy. Psychological support is important as improvement in mental health helps improve autonomic nerve function and, in turn, fatigue.

Validation of robust radiobiological optimization algorithms based on the mixed beam model for intensity-modulated carbon-ion therapy.

Currently, treatment planning systems (TPSs) that can compute the intensities of intensity-modulated carbon-ion therapy (IMCT) using scanned carbon-ion beams are limited. In the present study, the computational efficacy of the newly designed IMCT algorithms was analyzed for the first time based on the mixed beam model with respect to the physical and biological doses; moreover, the validity and effectiveness of the robust radiobiological optimization were verified. A dose calculation engine was independently generated to validate a clinical dose determined in the TPS. A biological assay was performed using the HSGc-C5 cell line to validate the calculated surviving fraction (SF). Both spot control (SC) and voxel-wise worst-case scenario (WC) algorithms were employed for robust radiobiological optimization followed by their application in a Radiation Therapy Oncology Group benchmark phantom under homogeneous and heterogeneous conditions and a clinical case for range and position errors. Importantly, for the first time, both SC and WC algorithms were implemented in the integrated TPS platform that can compute the intensities of IMCT using scanned carbon-ion beams for robust radiobiological optimization. For assessing the robustness, the difference between the maximum and minimum values of a dose-volume histogram index in the examined error scenarios was considered as a robustness index. The relative biological effectiveness (RBE) determined by the independent dose calculation engine exhibited a -0.6% difference compared with the RBE defined by the TPS at the isocenter, whereas the measured and the calculated SF were similar. Regardless of the objects, compared with the conventional IMCT, the robust radiobiological optimization enhanced the sensitivity of the examined error scenarios by up to 19% for the robustness index. The computational efficacy of the novel IMCT algorithms was verified according to the mixed beam model with respect to the physical and biological doses. The robust radiobiological optimizations lowered the impact of range and position uncertainties considerably in the examined scenarios. The robustness of the WC algorithm was more enhanced compared with that of the SC algorithm. Nevertheless, the SC algorithm can be used as an alternative to the WC IMCT algorithm with respect to the computational cost.

Dosimetric Comparison of Helical Tomotherapy and HyperArc Treatment Plans for Angiosarcoma of the Scalp.

BACKGROUND/AIM: Angiosarcoma of the scalp (AS) is a rare tumor that has often been treated by total scalp irradiation (TSI). TSI has technical and dosimetric challenges. This study aimed to compare the dosimetric performance of helical tomotherapy (HT) plans with that of HyperArc (HA) plans for TSI in AS. PATIENTS AND METHODS: A planning study was conducted for 11 patients with AS (70 Gy/35 fr). HT and HA planning was performed using TomoHDA and TrueBeam Edge systems, respectively. The performance of three different plans were compared: HT, HA, and HA with half-field beams (HF-HA). The dose distribution and dosimetric parameters for each plan were evaluated. RESULTS: All constraint parameters for the target and organs at risk (OARs) met the goals within acceptable limits for the three techniques. The HA and HF-HA plans provided significantly lower mean brain dose (12.46±2.48 Gy and 8.02±1.48 Gy) than did the HT plan (17.59±3.47 Gy). The doses receiving 0.1 cc of the volume for brainstem and chiasm were significantly lower in the HA and HF-HA plans than those in the HT plan. The HA and HF-HA plans provided a shorter beam-on time (155±3 s and 181±14 s) than did the HT plan (962±221 s). CONCLUSION: The HA plan provided significantly better OARs sparing than the HT plan for TSI in AS and had an advantage to using half-field beams.

Improvement of target coverage using automated non-coplanar volumetric modulated arc therapy planning in stereotactic radiotherapy for cervical metastatic spinal tumors.

This study aimed to compare dosimetric parameters for targets and organs at risk (OARs) between volumetric modulated arc therapy (VMAT) and automated VMAT (HyperArc, HA) plans in stereotactic radiotherapy for patients with cervical metastatic spine tumors. VMAT plans were generated for 11 metastases using the simultaneous integrated boost technique to deliver 35 to 40 and 20 to 25 Gy for high dose and elective dose planning target volume (PTVHD and PTVED), respectively. The HA plans were retrospectively generated using 1 coplanar and 2 noncoplanar arcs. Subsequently, the doses to the targets and OARs were compared. The HA plans provided significantly higher (p < 0.05) Dmin (77.4 ± 13.1%), D99% (89.3 ± 8.9%), and D98% (92.5 ± 7.7%) for gross tumor volume (GTV) than those of the VMAT plans (73.4 ± 12.2%, 84.2 ± 9.6 and 87.3 ± 8.8% for Dmin, D99% and D98%, respectively). In addition, D99% and D98% for PTVHD were significantly higher in the HA plans, whereas dosimetric parameters were comparable between the HA and VMAT plans for PTVED. The Dmax values for the brachial plexus, esophagus, and spinal cord were comparable, and no significant difference was observed in the Dmean for the larynx, pharyngeal constrictor, thyroid, parotid grand (left and right), and Submandibular gland (left and right). The HA plans provided significantly higher target coverage of GTV and PTVHD, with a comparable dose for OARs with VMAT plans. The results of this study may contribute to the improvement of local control in clinical practice.

Comparison of dosimetric parameters and robustness for rotational errors in fractionated stereotactic irradiation using automated noncoplanar volumetric modulated arc therapy for patients with brain metastases: single- versus multi-isocentric technique.

To compare the dosimetric parameters of automated noncoplanar volumetric modulated arc therapy plans using single-isocentric (SIC) and multi-isocentric (MIC) techniques for patients with two brain metastases (BMs) in stereotactic irradiation and to evaluate the robustness of rotational errors. The SIC and MIC plans were retrospectively generated (35 Gy/five fractions) for 58 patients. Subsequently, a receiver operating characteristic curve analysis between the tumor surface distance (TSD) and V25Gy was performed to determine the thresholds for the brain tissue. The SIC and MIC plans were recalculated based on the rotational images to evaluate the dosimetric impact of rotational error. The MIC plans showed better brain tissue sparing for TSD > 6.6 cm. The SIC plans provided a significantly better conformity index for TSD ≤ 6.6 cm, while significantly lower gradient index was obtained (3.22 ± 0.56vs. 3.30 ± 0.57, p < 0.05) in the MIC plans with TSD > 6.6 cm. For organs at risk (OARs) (brainstem, chiasm, lens, optic nerves, and retinas), D0.1 cc was significantly lower (p < 0.05) in the MIC plans than in the SIC plans. The prescription dose could be delivered (D99%) to the gross tumor volume (GTV) for patients with TSD ≤ 6.6 cm when the rotational error was < 1°, whereas 31% of the D99% of GTV fell below the prescription dose with TSD > 6.6 cm. MIC plans can be an optimal approach for reducing doses to OARs and providing robustness against rotational errors in BMs with TSD > 6.6 cm.

KRT13 is upregulated in pancreatic cancer stem-like cells and associated with radioresistance.

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.

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

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

Dose reduction of hippocampus using HyperArc planning in postoperative radiotherapy for primary brain tumors.

To compare dosimetric parameters for the hippocampus, organs at risk (OARs), and targets of volumetric modulated arc therapy (VMAT), noncoplanar VMAT (NC-VMAT), and HyperArc (HA) plans in patients undergoing postoperative radiotherapy for primary brain tumors. For 20 patients, HA plans were generated to deliver 40.05 to 60 Gy for the planning target volume (PTV). In addition, doses for the hippocampus and OARs were minimized. The VMAT and NC-VMAT plans were retrospectively generated using the same optimization parameters as those in the HA plans. For the hippocampus, the equivalent dose to be administered in 2 Gy fractions (EQD2) was calculated assuming α/ß = 2. Dosimetric parameters for the PTV, hippocampus, and OARs in the VMAT, NC-VMAT, and HA plans were compared. For PTV, the HA plans provided significantly lower Dmax and D1% than the VMAT and NC-VMAT plans (p < 0.05), whereas the D99% and Dmin were significantly higher (p < 0.05). For the contralateral hippocampus, the dosimetric parameters in the HA plans (8.1 ± 9.6, 6.5 ± 7.2, 5.6 ± 5.8, and 4.8 ± 4.7 Gy for D20%, D40%, D60% and D80%, respectively) were significantly smaller (p < 0.05) than those in the VMAT and NC-VMAT plans. Except for the optic chiasm, the Dmax in the HA plans (brainstem, lens, optic nerves, and retinas) was the smallest (p < 0.05). In addition, the doses in the HA plans for the brain and skin were the smallest (p < 0.05) among the 3 plans. HA planning, instead of coplanar and noncoplanar VMAT, significantly reduces the dosage to which the contralateral hippocampus as well as other OARs are exposed without compromising on target coverage.

The linker of nucleoskeleton and cytoskeleton complex is required for X-ray-induced epithelial-mesenchymal transition.

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/ß-catenin signaling pathway regulates E-cadherin expression via the expression of the E-cadherin repressor Snail, the expression of ß-catenin after X-irradiation was examined. After 24 hours of irradiation, ß-catenin expression increased in non-transfected cells or SUN1_916-depleted cells, whereas ß-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/ß-catenin signaling pathway.

Ultra-high Dose-rate Carbon-ion Scanning Beam With a Compact Medical Synchrotron Contributing to Further Development of FLASH Irradiation.

BACKGROUND/AIM: The focus of this report is establishing an irradiation arrangement to realize an ultra-high dose-rate (uHDR; FLASH) of scanned carbon-ion irradiation possible with a compact commonly available medical synchrotron. MATERIALS AND METHODS: Following adjustments to the operation it became possible to extract ≥1.0×109 carbon ions at 208.3 MeV/u (86 mm in range) per 100 ms. The design takes the utmost care to prevent damage to monitors, particularly in the nozzle, achieved by the uHDR beam not passing through this part of the apparatus. Doses were adjusted by extraction times, using a function generator. After one scan by the carbon-ion beam it became possible to create a field within the extraction time. The Advanced Markus chamber (AMC) and Gafchromic film are then able to measure the absolute dose and field size at a plateau depth, with the operating voltage of the chamber at 400 V at the uHDR for the AMC. RESULTS: The beam scanning utilizing this uHDR irradiation could be confirmed at a dose of 6.5±0.08 Gy (±3% homogeneous) at this volume over at least 16×16 mm2 corresponding to a dose-rate of 92.3 Gy/s (±1.3%). The dose was ca. 0.7, 1.5, 2.9, and 5.4 Gy depending on dose-rate and field size, with the rate of killed cells increasing with the irradiation dose. CONCLUSION: The compact medical synchrotron achieved FLASH dose-rates of >40 Gy/s at different dose levels and in useful field sizes for research with the apparatus and arrangement developed here.