Individual Radiation Research Articles

Персонализированная дозиметрия внутреннего облучения опухолевых образований и органов риска пациентов: разработка и реализация методического базиса для дозиметрического обеспечения клинических исследований терапевтических радиофармпрепаратов

The cluster of calculational and instrumental methods for estimation of personalized internal radiation doses to foci and organs at risk among patients undergoing to therapy by radiopharmaceuticals has been developed. The developed set of methods was used for dosimetrical support of clinical trials of therapeutic radiopharmaceuticals: a) Lu-177-DOTA-PSMA (or "Lutaprost") targeted for radioligand therapy of metastatic castrate-resistant prostate cancer; b) Re-188 albumin microspheres 5-10 μm (or "Artroren") targeted for radiosynovectomy in the local treatment of chronic inflammatory diseases of the joints and c) 188Re albumin microspheres 20-40 μm (or "Gepatoren") targeted for intra-arterial radionuclide embolization in the treatment of inoperable liver cancer. The results of estimations absolute activities of radiopharmaceuticals and their dynamics during SPECT/CT scanning of radiopharmaceuticals in the body of patients were verified by measurements using physical phantoms of humans with different body weights and various standard activities of radionuclides distributed inside the phantoms. The developed cluster of programs (for calculating the absorbed fraction of energy in biostructures), relevant databases and instrumental methods were used as the basis for estimations personalized internal radiation doses in foci and organs at risk among patients included in clinical trials of the studied radiopharmaceuticals. Individual internal radiation doses in foci among 39 patients, included in the first phase of clinical trials of the three studied radiopharmaceuticals, were estimated. The analysis of the distribution of estimated doses shows that absorbed doses in foci are very differing not only in different patients, but also in different foci in the same patient. Irradiation doses in foci increase with an increasing in the administered activities of radiopharmaceuticals and, depending on the volume of foci, are within the following ranges: 1) in a case of “Lutaprost” – from 1.4 to 32 Gy (planned administered activity – 5 GBq), from 5.1 to 59 Gy (planned activity – 7.5 GBq), from 13 to 94 Gy (planned activity – 10 GBq); 2) in a case of "Arthroren" – from 17.5 to 74 Gy (planned administered activities – from 0.37 to 0.925 GBq); 3) in a case of “Gepatoren” – from 10.7 to 43 Gy (planned administered activities – from 1 to 3 GBq). Individual absorbed doses in organs at risk were estimated as well. Dose values in organs at risk also vary greatly between different patients and between different critical organs. These doses ranged from 0.01 to 7.4 Gy (39 patients), which is many times less than “commonly applied dose constraints” in radiotherapy.

A Graded Index All-Dielectric Lens for Field Decorrelation and Decoupling of a Wideband MIMO Antenna

In this paper a broadband graded index all-dielectric (GID) lens that enables field decorrelation and decoupling of closely spaced wideband multiple-input-multiple-output (MIMO) antenna elements, is presented. Reduction in correlation coefficient ρ for field decorrelation and port decoupling is realized by tilting the individual antenna element radiation patterns away from each other and by suppressing the surface wave propagation inside the antenna substrate through judicious control of the permittivity profile of the GID lens using the concept of transformation electromagnetics (TE). The permittivity profile of the GID lens is designed using air-hole technology and is fabricated by additive manufacturing. To validate the proposed concept, six different examples of lens loaded wideband patch-based MIMO antenna elements arranged in two different orientations are investigated. Simulated and measured results verify the effectiveness of the proposed technique, which constitutes the reduction in ρ for both isotropic and non-isotropic propagation environments along with port-isolation enhancement without reducing the fractional bandwidth (FBW) in all of the six tested cases. Further results indicate a wide FBW having a minimum of 8.5% and a maximum of 33%, while radiation patterns with no extra backward radiation are obtained.

MAIN SOURCES OF IONIZING RADIATION AND ITS IMPACT ON THE POPULATION

All sources of ionizing radiation (IR) of human exposure are divided into natural and industrial. Natural sources of radiation are the main sources of human exposure. They include cosmic rays and radiation from natural radionuclides contained in the Earth's crust and atmosphere. Among radionuclides of natural origin, potassium-40 and radionuclides arising from the decay of natural radioactive uranium-238 and thorium-232 are the most important. Potassium, uranium, and thorium present in the earth's crust, when disintegrating, become sources of radiation and form the background external radiation of a person, and entering the body with air, water, and food - internal background radiation. The situation in Ukraine is typical for most countries of the world, although the levels of population exposure from natural sources are somewhat higher than the world average. Industrial sources include sources of both natural origin and those created by man, if they are purposefully used in industrial, scientific, medical and other spheres of human activity with the aim of obtaining a certain benefit. Human exposure to industrial sources can occur in production conditions (professional exposure of workers) and in the living environment. Under normal operating conditions, artificial radiation sources are fully controllable, and exposure from them is predictable. Among all industrial sources of radiation of the planet's population, X-ray diagnostic procedures rank first in terms of dose. A special place is occupied by the exposure of the population and personnel as a result of radiation accidents. Dozens of radiation accidents occur every year in the world, accompanied by the exposure of a small number of people. In some cases, individual radiation doses exceeded several Sieverts and even led to the death of people. The worst radiation accident in terms of the number of people exposed to accidental radiation is Chernobyl. The levels of exposure of a significant part of the population of Ukraine by man-made and enhanced sources of natural origin are determined by certain geological characteristics of the territories. Ensuring radiation safety and anti-radiation protection should be a priority when using sources of ionizing radiation in practice.

Влияние облучения на заболеваемость атеросклерозом среди участников ликвидации последствий аварии на Чернобыльской атомной электростанции

The statistical relationship between radiation dose to the cohort of workers (liquidators), participated in mitigation of effects of the Chernobyl accident are considered in the paper. The follow-up data collected from 1992 to 2021 and accumulated in the National Radiation and Epidemiological Register (NRER) were used for analysis. The cohort of liquidators consisted of 67,304 males. The average radiation dose in the cohort was 0.13 Gy, and the average age at radiation exposure was 34 years. During the follow-up period 10,790 atherosclerosis cases (ICD-10, code 170) were detected for the first time. To identify statistical relationship between radiation dose and atherosclerosis incidence, general “data mining” approaches were used, that do not use hypotheses about the probabilistic laws of random variable distributions, that determine the relationship between radiation dose and atherosclerosis incidence. A group of liquidators with accumulated during the period of work individual radiation doses below 0.15 Gy was selected as the reference group. The maximum radiation dose in the studied cohort was 1.4 Gy. Statistically significant relationship between radiation doses and atherosclerosis incidence (ICD-10, code 170) were found: relative radiation risk RR=1.05 at 95% lower confidence bound 1.027. The relative risks (RR) for individual diagnoses are: RR=1.22 (95% CI lower bound – 1.20) for ICD-10 – I70.0 (aortic atherosclerosis); RR=1.03 (95% CI lower bound – 1.01); for ICD-10 – I70.2 (limb artery atherosclerosis); RR=1.06 (95% CI lower bound – 1.04) for ICD-10 – I70.9 (generalized and unspecified atherosclerosis). The RR increases with the age at diagnosis. The results obtained can be the basis for the design of radiation-epidemiological studies for the detailed quantitative study of the detected dose-effect relationships.

Development of a X-ray Exposure Dose Control Tool for CT Examination by Using Spreadsheet Software

We developed X-ray dose monitoring and optimization software for computed tomography (CT) by using a spreadsheet software. The analysis was carried out on 1,212 patients using 2,128 CT examinations at our institution, in the period of April 2020 to April 2022. These cases were extracted in the limitation of patient's weight in the range of 50 to 70 kg. The individual radiation report, including CTDIvol and DLP, on the console displayed by a CT system was used and manually transferred to our software. The X-ray dose distribution was evaluated by using a boxplot chart and a scatter plot, and the data were referred to Japan DRLs 2020 (National Diagnostic Reference Levels in Japan 2020). Almost all patient's doses in our institution were distributed in the acceptable ranges in comparison with the Japan DRLs 2020. Neither extremely high nor low dose data were recorded. However, seven cases recorded outlier dose values. Three cases were caused by errors during manually inputting the data. Four from seven cases were explored the reason to record outlier dose values. Our software on a spreadsheet software worked well to explore the CT dose data, such as CTDIvol and DLP. Our software was able to find cases that were recorded as outlier dose values, but their values were not extremely high/low values. The cautionary notice of either high or low dose, as a function of our software, will be able to keep our patient's CT dose in the universal-standard "justification and optimization" level.

Метод оценки радиационных рисков смертности ликвидаторов чернобыльской аварии, учитывающий возможные ошибки в постановке и регистрации диагнозов причин смерти

In the past decade the lawful use of radiation risks of non-cancer diseases estimates to solve ra-diation safety problems has become more significant. The highest statistical power of low dose (less than 0.2 Gy) radiation risks research is possible in the cohort of the Chernobyl clean-up workers (liquidators) registered and been under medical monitoring in the system of the National Radiation Epidemiological Register (NRER) since 1986. The liquidators total number exceeds 130 thousand people. Because of the large-scale annual collection of health data, carried out in the NRER system, verification of the diseases diagnoses and medically certified causes of death, a natural question of radiation risk estimates compatibility with consideration to probable errors in a disease diagnosis and cause-of-death reporting on death certificates arises. The work is aimed at estimating the radiation risk of mortality from diseases of the circulatory system and diseases of the digestive organs in the Russian cohort of liquidators, with account of possible errors in the disease diagnosis and certified causes of death. The size of the cohort considered for mortality analysis was 91,013 people, the average age at the Chernobyl zone entry was 33.6 years, average radiation dose was 0.133 Gy. In this study, the method of maximizing the partial likelihood function was used to assess radiation risks, with consideration of individual radiation doses to liquidators and the assessment of background mortality using the Breslow method. The specificity of the diagnosis of the primary causes of death in the NRER system significantly exceeds the level of 0.99. Considering the specificity index of 0.99, the estimates of radiation risk coefficients ERR/Gy for mortality from diseases of the circulatory system and diseases of the digestive system in the cohort of Russian liquidators do not differ from the estimates obtained in the assumption that there are no first kind errors (false positive diagnosis) in the diagnoses of the primary causes of death in the NRER database. The results obtained confirm the high stability and validity of the assessments of radiation risks of mortality from diseases of the circulatory system and diseases of the digestive system, obtained earlier from the data on liquidators registered in the NRER.

DRIVERS OF HYPERFERREMIA IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES AFTER THE CHNPP ACCIDENT IN UKRAINE.

assessment of clinical-hematological and metabolic-biochemical parameters of the of bone tissue and hormonal regulation depending on the serum iron content and radiation dose values in children living on radiologically contaminated territories after the ChNPP accident in Ukraine. Children (n = 271) living on radiologically contaminated territories (RCT) of Ukraine were involved in the study. Three study groups were formed according to the serum iron level (SIL), namely group I with SIL 10.0-22.0 μmol/l (n = 92), group II with SIL 23.0-34.0 μmol/l (n = 144), and group III with SIL above 35.0 μmol/l (n = 35). Diseases in the family tree, bodyweight at birth, complaints on osalgia, bone fractures, jaw anomalies, dental caries, and obesity were accounted. Morphometric parameters of erythrocytes and hemogram elements were analyzed. Creatinine, alkaline phosphatase, calcium, total protein, iron, cholesterol, bilirubin, and transaminases were assayed in blood serum. The urine content of the 19 free amino acids, serum content of the free thyroxine (FT4), pituitary thyroid-stimulating hormone (TSH), and cortisol were assayed both with bone tissue density. Individual radiation doses were calculated. In 12.9 % of cases the SIL was > 35.0 μmol/l. Relatives with endocrine diseases were often present in the family tree of children with SIL > 23.0 μmol/l. There were increased urine content of the free amino acids (p < 0.05) and signs of protein degradation under high SIL. Contents of amino acids involved in collagen synthesis and antioxidant status (alanine, serine, glutamine, aspartic acid) and iron metabolism (arginine, leucine) were assayed at the highest levels (p < 0.05). Urinary levels of valine, lysine, and methionine, which are associated with iron metabolism, were decreased (p < 0.05). An inverse correlation (rs = -0.58; p < 0.01) was established between the serum TSH and cortisol levels regardless of the SIL. Serum TSH level directly correlated with urine content of amino acids involved in collagen synthesis. An inverse correlation (rs = -0.55; p < 0.001) was established between the serum TSH level and urine content of tyrosine that is essential for the thyroid hormone (triiodothyronine and thyroxine) synthesis.Cortisol was found having a negative effect on protein synthesis. Inverse correlation was established between the serum cortisol level and urine content of the free amino acids essential for collagen synthesis. There was no dependence of the average radiation dose values on the SIL. An inverse correlation was determined between the patient's radiation dose and SIL > 35.0 μmol/l (rs = -0.29; p < 0.05). The increased SIL in children living on RCT may occur due to both a genetic predisposition and the acquired factors driving protein and mineral metabolism of bone and their hormonal regulation.

The Normal, the Radiosensitive, and the Ataxic in the Era of Precision Radiotherapy: A Narrative Review.

(1) Background: radiotherapy is a cornerstone of cancer treatment. When delivering a tumoricidal dose, the risk of severe late toxicities is usually kept below 5% using dose-volume constraints. However, individual radiation sensitivity (iRS) is responsible (with other technical factors) for unexpected toxicities after exposure to a dose that induces no toxicity in the general population. Diagnosing iRS before radiotherapy could avoid unnecessary toxicities in patients with a grossly normal phenotype. Thus, we reviewed iRS diagnostic data and their impact on decision-making processes and the RT workflow; (2) Methods: following a description of radiation toxicities, we conducted a critical review of the current state of the knowledge on individual determinants of cellular/tissue radiation; (3) Results: tremendous advances in technology now allow minimally-invasive genomic, epigenetic and functional testing and a better understanding of iRS. Ongoing large translational studies implement various tests and enriched NTCP models designed to improve the prediction of toxicities. iRS testing could better support informed radiotherapy decisions for individuals with a normal phenotype who experience unusual toxicities. Ethics of medical decisions with an accurate prediction of personalized radiotherapy's risk/benefits and its health economics impact are at stake; (4) Conclusions: iRS testing represents a critical unmet need to design personalized radiotherapy protocols relying on extended NTCP models integrating iRS.

Associations Between External Radiation Doses and the Risk of Psychological Distress or Post-traumatic Stress After the Fukushima Daiichi Nuclear Power Plant Accident: the Fukushima Health Management Survey.

The relationship between radiation levels and mental health status after a nuclear disaster is unknown. We examined the association between individual external radiation doses and psychological distress or post-traumatic stress after the Fukushima Daiichi nuclear power plant accident in March 2011 in Japan. The Mental Health and Lifestyle Survey was conducted from January 2012. Based on the estimated external radiation doses for the first 4 months, a total of 64,184 subjects were classified into <1 mSv, 1 to <2 mSv, and ≥2 mSv groups. Odds ratios (ORs) and 95% confidence intervals (CIs) of psychological distress and post-traumatic stress, with the <1 mSv group as the reference, were calculated using logistic regression analysis adjusted for age, sex, evacuation, perception of radiation risk, and subjective health status. The prevalence of psychological distress/post-traumatic stress in the <1 mSv, 1 to <2 mSv, and ≥2 mSv groups was 15.1%/22.1%, 14.0%/20.1%, and 15.0%/21.7%, respectively. In women, although the ≥2 mSv group tended to have a higher risk of psychological distress with the age-adjusted OR of 1.13 (95% CI, 0.99-1.30), the adjusted OR decreased to 1.00 (95% CI, 0.86-1.16) after controlling for all variables. On the other hand, there were no dose-dependent associations between radiation dose and post-traumatic stress. Although external radiation doses were not associated with psychological distress, evacuation and perception of radiation risk may increase the risk of psychological distress in women in the higher dose group.

Dosiomics Risk Model for Predicting Radiation Induced Temporal Lobe Injury and Guiding Individual Intensity-Modulated Radiation Therapy

We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy. A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the quantitative analyses of normal tissue effects in the clinic and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test. The radiomics and dosiomics signatures were constructed based on 30 selected computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P <.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, D1cc, and age had favorable performance, with C-index values of 0.776, 0.811, 0.805, and 0.794 in the training, validation, prospective test, and external test cohorts, respectively, which were better than those of the quantitative analyses of normal tissue effects in the clinic model and Wen's model (all P <.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P <.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P > .05). Two simulated plans with the same dose-volume histogram but different dose distributions had different TLI-free survival rates predicted by dosiomics risk model (all P ≤ .002). The dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity modulated radiation therapy.

Oxidative Modification Status of Human Serum Albumin Caused by Chronic Low-Dose Radiation Exposure in Mamuju, Sulawesi, Indonesia.

The recently discovered high-level natural background radiation area (HBRA) of Mamuju in Indonesia provides a unique opportunity to study the biological effects of chronic low-dose radiation exposure on a human population. The mean total effective dose in the HBRA was approximately 69.6 mSv y-1 (range: 47.1 to 115.2 mSv y-1), based on a re-evaluation of the individual radiation exposure dose; therefore, proteomic analyses of serum components and oxidative modification profiling of residents living in the HBRA were reconducted using liquid chromatography-tandem mass spectrometry. The analysis of the oxidative modification sequences of human serum albumin revealed significant moderate correlations between the radiation dose and the modification of 12 sequences, especially the 111th methionine, 162nd tyrosine, 356th tyrosine, and 470th methionine residues. In addition, a dose-dependent variation in 15 proteins of the serum components was detected in the serum of residents exposed to chronic low-dose radiation. These findings suggest that the alterations in the expression of specific proteins and the oxidative modification responses of serum albumin found in exposed humans may be important indicators for considering the effects of chronic low-dose radiation exposure on living organisms, implying their potential utility as biomarkers of radiation dose estimation.

Risk of Cerebrovascular Events among Childhood and Adolescent Patients Receiving Cranial Radiotherapy: A PENTEC Normal Tissue Outcomes Comprehensive Review

<h3>Purpose/Objective(s)</h3> Radiation (RT)-induced cerebrovascular toxicity is a well-documented sequelae that can be both life-altering and potentially fatal. Although multiple retrospective series and case reports discuss the association between cranial RT in children and subsequent cerebral vasculopathy, useful dose-response data to guide practitioners in the counseling or prevention of these events is lacking. We performed a meta-analysis of the relevant literature to create practical models for predicting the risk of cerebral vasculopathy after cranial RT. This report presents our updated modeling results which will be the basis for our PENTEC publication. <h3>Materials/Methods</h3> A literature search was performed for studies reporting pediatric RT associated cerebral vasculopathy. When available, we utilized individual patient RT doses delivered to the Circle of Willis (CW) or optic chiasm (as a surrogate), as reported or digitized from original publications, to formulate a dose-response. A logistic fit and a Normal Tissue Complication Probability (NTCP) model was developed to predict future risk of cerebrovascular toxicity and stroke, respectively. This NTCP risk was assessed as a function of prescribed dose. <h3>Results</h3> The search identified 766 abstracts, five of which were used for modeling. We identified 101 of 3989 pediatric patients who experienced at least one cerebrovascular toxicity: transient ischemic attack (TIA), stroke, <i>Moyamoya</i>, or arteriopathy. Logistic model parameters with 95% confidence intervals were: dose for 50% response (D50 = 75.6 Gy; 68.4-89.4 Gy) and normalized dose-response slope at D50 (γ50 = 2.69; 2.05–3.60). For a range of shorter follow-ups, as specified in the original publications (approximate attained ages of 17 years), our logistic fit model predicted the incidence of any cerebrovascular toxicity as a function of dose to the CW, or surrogate structure: 0.2% at 30 Gy, 1.3% at 45 Gy, and 4.4% at 54 Gy. At an attained age of 35 years, our NTCP model predicted a stroke incidence of 0.9-1.3%, 1.8-2.7%, and 2.8-4.1%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared to a baseline risk of 0.2-0.3%). At an attained age of 45 years, the predicted incidence of stroke was 2.1-4.2%, 4.5-8.6%, and 6.7-13.0%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared to a baseline risk of 0.5-1.0%). <h3>Conclusion</h3> The risk of cerebrovascular toxicity continues to increase with longer follow-up. NTCP stroke predictions are very sensitive to model variables (baseline stroke risk and proportional stroke hazard), both of which found in the literature may be systematically erring on minimization of true risk. Further, since the stroke hazard was based on prescribed dose rather than CW dose our reported stroke risk is likely underestimated. We hope this information will assist practitioners in counseling, screening, surveilling, and facilitating risk reduction of RT-related cerebrovascular late effects in this highly sensitive population.

Risk of Diabetes Mellitus after Radiotherapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

<h3>Purpose/Objective(s)</h3> The long-term effect of radiation on pancreas has been mostly studied for pediatric patients with the lack of individual radiation dosimetric data. The purpose of this study was to investigate the effect of radiotherapy (RT) on the risk of newly developed diabetes mellitus (DM) in patients with gastric mucosa-associated lymphoid tissue lymphoma (GML) using individual radiation dosimetric analysis. <h3>Materials/Methods</h3> We retrospectively reviewed 225 patients without history of DM who received curative aim treatment for stage IE GML between August 2007 and June 2020. Involved site RT to the whole stomach was delivered in 83 patients (36.9%). The pancreas was delineated in each patient's computerized tomography scan for dosimetric analysis. <h3>Results</h3> At a median follow-up time of 49.0 months (range, 3.0-155.3 months), the 3-year cumulative incidence of DM was 3.9% in all patients, and 7.9% and 1.6% in patients who received and did not receive RT, respectively (p=0.009). The mean pancreatic dose (D_mean) was independently associated with DM (p=0.027). As a result of recursive partitioning analysis, patients were classified into low (D_mean <21 Gy), intermediate (D_mean ≥21 Gy and BMI <27.0kg/m²), and high-risk groups (D_mean ≥21 Gy and BMI ≥27.0kg/m²) with 5-year DM incidence of 1.5%, 6.3%, and 54.3%, respectively (p<0.001). <h3>Conclusion</h3> Our results indicate that incidental irradiation to the pancreas can increase the risk of DM, which was dependent on pancreas D_mean. In addition, not only reducing pancreas D_mean but also controlling BMI may need to be combined to effectively prevent DM after RT.

Individual Dose Response and Radiation Origin of Childhood and Adolescent Thyroid Cancer in Fukushima II: Possibility of High I-131 Exposure as in Chernobyl

Background: Thyroid cancer incidence of individual dose groups in Fukushima residents exposed at ≤18 years of age demonstrated a linear response to thyroid dose estimated in the United Nations Scientific Committee on the effects of Atomic Radiation (UNSCEAR) 2020/2021. Increased childhood thyroid cancer in Fukushima was found to come dominantly from radiation exposure from the nuclear accident. The UNSCEAR 2020/2021 concluded that the apparent excess of thyroid cancers would not be expected at thyroid doses estimated by the UNSCEAR. The purpose of this paper is to solve the puzzle of the high childhood thyroid cancer incidence in Fukushima despite the estimated low thyroid dose. Methods: The conversion coefficient k connecting thyroid doses estimated in UNSCEAR 2020/2021 and doses based on direct thyroid dose measurements in Chernobyl: 1 GyUN2021 = k × 1 Gy (gray), was estimated by comparing incidences and dose dependences of thyroid cancers in Fukushima and Chernobyl after nuclear disasters. Results: The ratio of the observed cases /expected cases from cancer registry: of about 60 in Fukushima prefecture, was higher than the ratios observed after the Chernobyl accident. The thyroid doses estimated by UNSCEAR were corrected by adding a baseline dose to recover the severely underestimated ingestion dose. The conversion coefficients were: k =60~70 from the comparison of the excess absolute risks (EAR) and their dose dependences in Fukushima and in Chernobyl, and k =10~180 from the comparison of excess relative risk per gray (ERR/Gy) in Fukushima with those in Chernobyl. The thyroid doses might have been underestimated by about 1/50~1/100 in UNSCEAR 2020/2021. Conclusion: The dozens-fold increase of childhood thyroid cancer cases after the Fukushima nuclear accident was found to arise from radioactive iodine exposure comparable to that in Chernobyl.

Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters

BackroundAccurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas.MethodsTwenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied.ResultsIn total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson’s test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein.ConclusionIn this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.

A meta-learning approach to improving radiation response prediction in cancers

PurposePredicting the efficacy of radiotherapy in individual patients has drawn widespread attention, but the limited sample size remains a bottleneck for utilizing high-dimensional multi-omics data to guide personalized radiotherapy. We hypothesize the recently developed meta-learning framework could address this limitation. Methods and materialsBy combining gene expression, DNA methylation, and clinical data of 806 patients who had received radiotherapy from The Cancer Genome Atlas (TCGA), we applied the Model-Agnostic Meta-Learning (MAML) framework to tasks consisting of pan-cancer data, to obtain the best initial parameters of a neural network for a specific cancer with smaller number of samples. The performance of meta-learning framework was compared with four traditional machine learning methods based on two training schemes, and tested on Cancer Cell Line Encyclopedia (CCLE) and Chinese Glioma Genome Atlas (CGGA) datasets. Moreover, biological significance of the models was investigated by survival analysis and feature interpretation. ResultsThe mean AUC (Area under the ROC Curve) [95% confidence interval] of our models across nine cancer types was 0.702 [0.691–0.713], which improved by 0.166 on average over other the four machine learning methods on two training schemes. Our models performed significantly better (p < 0.05) in seven cancer types and performed comparable to the other predictors in the rest of two cancer types. The more pan-cancer samples were used to transfer meta-knowledge, the greater the performance improved (p < 0.05). The predicted response scores that our models generated were negatively correlated with cell radiosensitivity index in four cancer types (p < 0.05), while not statistically significant in the other three cancer types. Moreover, the predicted response scores were shown to be prognostic factors in seven cancer types and eight potential radiosensitivity-related genes were identified. ConclusionsFor the first time, we established the meta-learning approach to improving individual radiation response prediction by transferring common knowledge from pan-cancer data with MAML framework. The results demonstrated the superiority, generalizability, and biological significance of our approach.

Association of clinic type with receipt of neoadjuvant therapy among patients with localized pancreatic cancer: Value of multidisciplinary clinic.

63 Background: Patients with localized pancreatic adenocarcinoma (PDAC) generally benefit from multi-modality therapy, which may be best coordinated through a pancreas multi-disciplinary clinic (PMDC). Whether treatment practice patterns vary based on whether a patient was seen through PMDC versus individual specialty-specific clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients who came to Johns Hopkins Hospital through either PMDC or one of the individual surgical, medical, or radiation oncology clinics for localized PDAC between 2018-2020 and eventually underwent resection. During this time, it was standard practice for borderline resectable (BRPC) patients to undergo at least 4 months of neoadjuvant chemotherapy, with or without radiation, before transitioning to exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation, followed by potential exploration. The primary outcome was completion of neoadjuvant therapy as per the above stage-specific institutional standards. Multivariable analyses were performed to find association between PMDC visit and completion of neoadjuvant therapy, controlling for age, sex, race, stage, baseline performance status and type of chemotherapy. Results: A total of 240 patients met inclusion criteria. Of these, 157 (65.4%) had PMDC visits. Distribution of stage across the cohort included 81 (34.3%), 91 (38.5%), and 64 (27.1%) patients with resectable PDAC, BRPC and LAPC, respectively. Patients in the PMDC group received radiation therapy more commonly (59.7% vs 34.9%, p = 0.004), as compared to patients seen through individual specialty-specific clinics. Mean duration of chemotherapy was higher for patients seen through PMDC (4.4 (SD: 1.7) vs 3.9 (SD: 2.0) months) compared with individual clinics. Completion of neoadjuvant therapy per institutional stage-specific standards was seen in 46% (n = 24) of the patients visiting individual specialty-specific clinics compared to 71% (n = 85) of patients who were seen through PMDC (p = 0.002). The adjusted odds ratio of completion of neoadjuvant therapy per institutional standards for patients seen through PMDC visit was 3.35 times the odds for patients seen through individual clinics (95% CIs 1.46-7.07; p = 0.004). Of note, a higher proportion of patients who were seen through PMDC enrolled in a clinical trial (n = 26, 16.6%) compared with patients seen through individual clinics (n = 6; 7.2%) (p = 0.043). Conclusions: Provision of care through a multi-disciplinary clinic was associated with significantly higher odds of completing neoadjuvant therapy per institutional standards as compared to care through individual specialty-specific clinics. In addition, care through a PMDC may also be associated with increased trial enrollment.

Aeroacoustic and aerodynamic interaction effects between electric vertical takeoff and landing rotors

Electric vertical take-off and landing (eVTOL) aircraft are characterized by their unconventional wing and electric rotor configurations, which involve both side-by-side and tandem rotor configurations. These configurations create unique aerodynamic and acoustic flow-fields. We numerically investigate the interaction effects between rotor pairs as well as their individual and combined acoustic radiation. We examine horizontal and vertical spacing, rotor tilt angles, and forward flight effects. Performance is characterized by thrust coefficient, blade passage frequency (BPF) sound pressure level (SPL), and overall sound pressure level (OASPL). This study is performed with a mid-fidelity aerodynamic solver, Dust, which is used to predict the aerodynamic flow-field. The tonal acoustic pressure at observer positions is predicted via the Farassat F-1A solution of the Ffowcs Williams and Hawkings equation utilizing the aerodynamic flow-field. The configurations studied show strong aerodynamic interaction effects in thrust, as well as out-of-plane acoustic radiation from the aft rotor. Base predictions of thrust and noise are validated via experimental measurement. As rotor separation decreases, we observe that aft rotor thrust decreases and BPF SPL increases. The most forward rotor, however, is marginally impacted by the interactions. [This research is supported by Archer Aviation Inc.]

Study For New Cooling Technique In Tropical Climate

In the modern world, it is quite difficult to achieve suitable indoor standards within a structure in tropical areas. This study investigates the development of indirect cooling techniques in residential construction as a means of preserving the environment by lowering cooling loads within the framework of interior design, using Navi Mumbai as a case study. This study presents conventional cooling techniques such radiant night cooling, radiant cooling with individual radiators, evaporate cooling, convective cooling, and rooftop pools. Over the past few years, Navi Mumbai's comfortable surroundings have been regulated by taking into account associations between the atmosphere, comfortable conditions, and framework cooling levels that specify how much cooling is required to accomplish those conditions. determining the right mixture that will produce.

Risk of Cerebrovascular Events Among Childhood and Adolescent Patients Receiving Cranial Radiation Therapy: A PENTEC Normal Tissue Outcomes Comprehensive Review

Radiation-induced cerebrovascular toxicity is a well-documented sequelae that can be both life-altering and potentially fatal. We performed a meta-analysis of the relevant literature to create practical models for predicting the risk of cerebral vasculopathy after cranial irradiation. A literature search was performed for studies reporting pediatric radiation therapy (RT) associated cerebral vasculopathy. When available, we used individual patient RT doses delivered to the Circle of Willis (CW) or optic chiasm (as a surrogate), as reported or digitized from original publications, to formulate a dose-response. A logistic fit and a Normal Tissue Complication Probability (NTCP) model was developed to predict future risk of cerebrovascular toxicity and stroke, respectively. This NTCP risk was assessed as a function of prescribed dose. The search identified 766 abstracts, 5 of which were used for modeling. We identified 101 of 3989 pediatric patients who experienced at least one cerebrovascular toxicity: transient ischemic attack, stroke, moyamoya, or arteriopathy. For a range of shorter follow-ups, as specified in the original publications (approximate attained ages of 17 years), our logistic fit model predicted the incidence of any cerebrovascular toxicity as a function of dose to the CW, or surrogate structure: 0.2% at 30 Gy, 1.3% at 45 Gy, and 4.4% at 54 Gy. At an attained age of 35 years, our NTCP model predicted a stroke incidence of 0.9% to 1.3%, 1.8% to 2.7%, and 2.8% to 4.1%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.2%-0.3%). At an attained age of 45 years, the predicted incidence of stroke was 2.1% to 4.2%, 4.5% to 8.6%, and 6.7% to 13.0%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.5%-1.0%). Risk of cerebrovascular toxicity continues to increase with longer follow-up. NTCP stroke predictions are very sensitive to model variables (baseline stroke risk and proportional stroke hazard), both of which found in the literature may be systematically erring on minimization of true risk. We hope this information will assist practitioners in counseling, screening, surveilling, and facilitating risk reduction of RT-related cerebrovascular late effects in this highly sensitive population.