Evaluation of two-dimensional electronic portal imaging device using integrated images during volumetric modulated arc therapy for prostate cancer

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 cm3) 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

Setup accuracy and dose attenuation of a wooden immobilization system for lung stereotactic body radiotherapy

Background: We evaluated the setup error and dose absorption of an immobilization system with a shell and wooden baseplate (SW) for lung stereotactic body radiotherapy (SBRT). Materials and methods: Setup errors in 109 patients immobilized with an SW or BodyFix system (BF) were compared. Dose attenuation rates of materials for baseplates were measured with an ion-chamber. Ionization measurements were performed from 90° to 180° gantry angle in 10° increments, with the ball water equivalent phantom placed at the center of the wood and carbon baseplates whose effects on dose distribution were compared using an electron portal imaging device. Results: The ratio for the anterior-posterior, cranial-caudal, and right-left of the cases within 3-mm registered shifts in interfractional setup error were 90.9%, 89.2%, and 97.4% for the SW, and 93.2%, 91.6%, and 98.0% for the BF, respectively. For intrafractional setup error, 98.3%, 97.4%, and 99.1% for the SW and 96.6%, 95.8%, and 98.7% for the BF were within 3-mm registered shifts, respectively. In the center position, the average (minimum/maximum) dose attenuation rates from 90° to 180° for the wooden and carbon baseplates were 0.5 (0.1/2.8)% and 1.0 (–0.1/10.1)% with 6 MV, respectively. The gamma passing rates of 2%/2 mm for the wooden and carbon baseplates were 99.7% and 98.3% (p < 0.01). Conclusions: The immobilization system with an SW is effective for lung SBRT since it is comparable to the BF in setup accuracy. Moreover, the wooden baseplate had lower radiation attenuation rates and affected the dose distribution less than the carbon baseplate.

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Dosimetric impact of baseline drift in volumetric modulated arc therapy with breath holding

BackgroundWe investigated the change of dose distributions in volumetric modulated arc therapy (VMAT) under baseline drift (BD) during breath holding.Materials and methodsTen VMAT plans recalculated to a static field at a gantry angle of 0° were prepared for measurement with a 2D array device and five original VMAT plans were prepared for measurement with gafchromic films. These measurement approaches were driven by a waveform reproducing breath holding with BD. We considered breath holding times of 15 and 10 s, and BD at four speeds; specifically, BD0 (0 mm/s), BD0.2 (0.2 mm/s), BD0.3 (0.3 mm/s), and BD0.4 (0.4 mm/s). The BD was periodically reproduced from the isocenter along the craniocaudal direction and the shift during breath holding (ShiftBH) ranged 0–6 mm.The dose distribution of BD0.2, BD0.3 and BD0.4 were compared to that of BD0 using gamma analysis with the criterion of 2%/2 mm.ResultsThe mean pass rates of each ShiftBH were 99.8% and 98.9% at 0 mm, 96.8% and 99.4% at 2 mm, 94.9% and 98.6% at 3 mm, 91.5% and 98.4% at 4 mm, 70.8% and 94.1% at 4.5 mm, and 55.0% and 83.6% at 6 mm for the array and film measurements, respectively.ConclusionWe found significant differences in ShiftBH above 4 mm (ρ

Carbon Ion Irradiation Suppresses Metastatic Potential of Human Non-small Cell Lung Cancer A549 Cells through the Phosphatidylinositol-3-Kinase/Akt Signaling Pathway

We previously showed that carbon ion irradiation can inhibit the expression of the anillin (ANLN) gene, which is regulated by the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling path- way associated with metastasis. The purpose of this study is to compare the effects of carbon ion irradia- tion on the PI3K/Akt signaling pathway to those of photon irradiation. Our study showed that carbon ion irradiation of human lung adenocarcinoma cells A549 decreased their invasion more effectively than pho- ton irradiation did. We found that carbon ion irradiation reduced the nuclear localization of ANLN at lower dose, but did not affect its expression. Low-dose carbon ion irradiation also reduced the level of phosphorylated Akt compared to untreated controls, whereas photon irradiation did not. These results sug- gest that carbon ion irradiation effectively suppresses the metastatic potential of A549 cells by suppressing the PI3K/Akt signaling pathway