Body Dose Research Articles

MicroSPECT/CT Imaging of Cell-Line and Patient-Derived EGFR-Positive Tumor Xenografts in Mice with Panitumumab Fab Modified with Hexahistidine Peptides To Enable Labeling with 99mTc(I) Tricarbonyl Complex.

We aimed to investigate the feasibility of conjugating synthetic hexahistidine peptides (His6) peptides to panitumumab Fab (PmFab) to enable labeling with [99mTc(H2O)3(CO)3]+ complex and study these radioimmunoconjugates for imaging EGFR-overexpressing tumor xenografts in mice by microSPECT/CT. Fab were reacted with a 10-fold excess of sulfo-SMCC to introduce maleimide functional groups for reaction with the terminal thiol on peptides [CGYGGHHHHHH] that harbored the His6 motif. Modification of Fab with His6 peptides was assessed by SDS-PAGE/Western blot, and the number of His6 peptides introduced was quantified by a radiometric assay incorporating 123I-labeled peptides into the conjugation reaction. Radiolabeling was achieved by incubation of PmFab-His6 in PBS, pH 7.0, with [99mTc(H2O)3(CO)3]+ in a 1.4 MBq/μg ratio. The complex was prepared by adding [99mTcO4]- to an Isolink kit (Paul Scherrer Institute). Immunoreactivity was assessed in a direct (saturation) binding assay using MDA-MB-468 human triple-negative breast cancer (TNBC) cells. Tumor and normal tissue uptake and imaging properties of 99mTc-PmFab-His6 (70 μg; 35-40 MBq) injected i.v. (tail vein) were compared to irrelevant 99mTc-Fab 3913 in NOD/SCID mice engrafted subcutaneously (s.c.) with EGFR-overexpressing MDA-MB-468 or PANC-1 human pancreatic ductal carcinoma (PDCa) cell-line derived xenografts (CLX) at 4 and 24 h post injection (p.i.). In addition, tumor imaging studies were performed with 99mTc-PmFab-His6 in mice with patient-derived tumor xenografts (PDX) of TNBC, PDCa, and head and neck squamous cell carcinoma (HNSCC). Biodistribution studies in nontumor bearing Balb/c mice were performed to project the radiation absorbed doses for imaging studies in humans with 99mTc-PmFab-His6. PmFab was derivatized with 0.80 ± 0.03 His6 peptides. Western blot and SDS-PAGE confirmed the presence of His6 peptides. 99mTc-PmFab-His6 was labeled to high radiochemical purity (≥95%), and the Kd for binding to EGFR on MDA-MB-468 cells was 5.5 ± 0.4 × 10-8 mol/L. Tumor uptake of 99mTc-PmFab-His6 at 24 h p.i. was significantly (P < 0.05) higher than irrelevant 99mTc-Fab 3913 in mice with MDA-MB-468 tumors (14.9 ± 3.1%ID/g vs 3.0 ± 0.9%ID/g) and in mice with PANC-1 tumors (5.6 ± 0.6 vs 0.5 ± 0.1%ID/g). In mice implanted orthotopically in the pancreas with the same PDCa PDX, tumor uptake at 24 h p.i. was 4.2 ± 0.2%ID/g. Locoregional metastases of these PDCa tumors in the peritoneum exhibited slightly and significantly lower uptake than the primary tumors (3.1 ± 0.3 vs 4.2 ± 0.3%ID/g; P = 0.02). In mice implanted with different TNBC or HNSCC PDX, tumor uptake at 24 h p.i. was variable and ranged from 3.7 to 11.4%ID/g and 3.8-14.5%ID/g, respectively. MicroSPECT/CT visualized all CLX and PDX tumor xenografts at 4 and 24 h p.i. Dosimetry estimates revealed that in humans, the whole body dose from administration of 740-1110 MBq of 99mTc-PmFab-His6 would be 2-3 mSv, which is less than for a 99mTc-medronate bone scan (4 mSv).

Medical management of acute responses to radiation.

Medical management of acute responses to radiation.

Implementation of total body photon irradiation as part of an institutional bone marrow transplant program for the treatment of canine lymphoma and leukemias.

A total body irradiation (TBI) protocol was developed to support a bone marrow transplant (BMT) program for the treatment of canine hematologic malignancies. The purpose of this prospective study is to describe implementation of the protocol and resultant dosimetry. Nongraphic manual treatment planning using 6 MV photons, isocentric delivery, 40×40cm field size, wall-mounted lasers to verify positioning, a lucite beam spoiler (without use of bolus material), a dose rate of 8.75 cGy/min at patient isocenter, and a source-to-axis distance of 338cm were used for TBI. A monitor unit calculation formula was derived using ion chamber measurements and a solid water phantom. Five thermoluminescent dosimeters (TLDs) were used at various anatomic locations in each of four cadaver dogs, to verify fidelity of the monitor unit formula prior to clinical implementation. In vivo dosimetric data were then collected with five TLDs at various anatomic locations in six patients treated with TBI. A total dose of 10Gy divided into two 5Gy fractions was delivered approximately 16h apart, immediately followed by autologous stem cell transplant. The mean difference between prescribed and delivered doses ranged from 99% to 109% for various sites in cadavers, and from 83% to 121% in clinical patients. The mean total body dose in cadavers and clinical patients when whole body dose was estimated by averaging doses measured by variably placed TLDs ranged from 98% to 108% and 93% to 102% of the prescribed dose, respectively, which was considered acceptable. This protocol could be used for institutional implementation of TBI.

A study on dose conversion from a material to human body using mesh phantom for retrospective dosimetry

In case of a radiation emergency, thermoluminescence (TL) and optically stimulated luminescence (OSL) measurements from materials in a mobile phone have been developed to enable classification of exposed individuals within a short period of time. A reconstructed dose from a mobile phone does not, however, correspond directly to a human body dose. Therefore, several studies were tried to convert a phone dose to a human body dose. Because of the difficulty in obtaining conversion factors experimentally, Monte Carlo simulations have been carried out using human phantoms for various accident situations. In recent years phantoms made of mesh have been developed to solve some problems in traditional voxel phantoms such as limited posture. In the present study, simulations using the GEANT4 computer code were performed to obtain conversion factors using mesh phantoms. The geometry of a mobile phone was designed, reflecting latest structures, and a display glass was selected as a dosimetric material due to its wide detection area with a high radiation sensitivity. Four different positions (chest, hip, thigh, and hand) of a mobile phone on the phantom were considered. In addition, six exposure conditions of anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), isotropic (ISO), and rotational (ROT) exposure geometries and three different postures of standing, kneeling, and squatting were selected to reflect actual working situations. Three commonly used radiation sources (Iridium-192, Cesium-137, and Cobalt-60) were applied.

Comparison of Techniques for Involved-Site Radiation Therapy in Patients With Lower Mediastinal Lymphoma

PurposePatients with lower mediastinal lymphoma (LML) benefit dosimetrically from proton therapy (PT) compared with intensity modulated radiation therapy (IMRT). The added dosimetric benefit of deep-inspiration breath-hold (DIBH) is unknown; therefore, we evaluated IMRT versus PT and free-breathing (FB) versus DIBH among patients with LML. Methods and MaterialsTwenty-one patients with LML underwent 4-dimensional computed tomography and 3 sequential DIBH scans at simulation. Involved-site radiation therapy target volumes and organ-at-risk contours were developed for both DIBH and FB scans. FB-IMRT, DIBH-IMRT, FB-PT, and DIBH-PT plans were generated for each patient for comparison. ResultsThe median difference in lung volume between the DIBH and FB scans was 1275 mL; the average difference in clinical target volume was 5.7 mL. DIBH-IMRT produced a lower mean lung dose (10.8 vs 11.9 Gy; P < .001) than FB-IMRT, with no difference in mean heart dose (MHD; 16.1 vs 15.0 Gy; P = .992). Both PT plans produced a significantly lower mean dose to the lung, heart, left ventricle, esophagus, and nontarget body than DIBH-IMRT. DIBH-PT reduced the median MHD by 4.2 Gy (P < .0001); left ventricle dose by 5.1 Gy (P < .0001); and lung V5 by 26% (P < .0001) versus DIBH-IMRT. The 2 PT plans were comparable, with DIBH-PT reducing mean lung dose (7.0 vs 7.7 Gy; P = .063) and with no difference in MHD (10.3 vs 9.5 Gy; P = .992). ConclusionsAmong patients with LML, DIBH (IMRT or PT) improved lung dosimetry over FB but had little influence on MHD. PT (DIBH and FB) significantly reduced lung, heart, esophagus, and nontarget body dose compared with DIBH IMRT, potentially reducing the risk of late complications.

Low-Dose Imaging in a New Preclinical Total-Body PET/CT Scanner.

Ionizing radiation constitutes a health risk to imaging scientists and study animals. Both PET and CT produce ionizing radiation. CT doses in pre-clinical in vivo imaging typically range from 50 to 1,000 mGy and biological effects in mice at this dose range have been previously described. [18F]FDG body doses in mice have been estimated to be in the range of 100 mGy for [18F]FDG. Yearly, the average whole body doses due to handling of activity by PET technologists are reported to be 3–8 mSv. A preclinical PET/CT system is presented with design features which make it suitable for small animal low-dose imaging. The CT subsystem uses a X-source power that is optimized for small animal imaging. The system design incorporates a spatial beam shaper coupled with a highly sensitive flat-panel detector and very fast acquisition (<10 s) which allows for whole body scans with doses as low as 3 mGy. The mouse total-body PET subsystem uses a detector architecture based on continuous crystals, coupled to SiPM arrays and a readout based in rows and columns. The PET field of view is 150 mm axial and 80 mm transaxial. The high solid-angle coverage of the sample and the use of continuous crystals achieve a sensitivity of 9% (NEMA) that can be leveraged for use of low tracer doses and/or performing rapid scans. The low-dose imaging capabilities of the total-body PET subsystem were tested with NEMA phantoms, in tumor models, a mouse bone metabolism scan and a rat heart dynamic scan. The CT imaging capabilities were tested in mice and in a low contrast phantom. The PET low-dose phantom and animal experiments provide evidence that image quality suitable for preclinical PET studies is achieved. Furthermore, CT image contrast using low dose scan settings was suitable as a reference for PET scans. Total-body mouse PET/CT studies could be completed with total doses of <10 mGy.

Investigation on radon concentration in drinking water to assess the whole body dose and excess lifetime cancer risk along coastal Kerala, India

Some of the coastal parts of Kerala are well reported as high background radiation areas. Hence, the radiological protection of the population in this region is of great concern. In view of this, study has been undertaken to understand the distribution and enrichment of radon concentration in open well water from the region. Further, the whole body doses due to radon exposure were estimated from the radon concentration. The excess lifetime cancer risk (ELCR) was assessed from the obtained whole body dose. The Emanometry method was used for the quantification of dissolved radon in water from various open wells and the obtained concentration was found to vary in the range 0.12–4.35 Bq L−1. The effective dose values from the present study were below the recommended limit of 0.1 mSv year−1 suggested by the WHO and EU council. The ELCR value obtained from the present study was well below the world average value for most of the sampling stations except Varkala, where the value was comparable with the world average. The results from the present investigation indicate that, the dose due to radon by the consumption of water is not significant.

Scattered radiation on cardiologists during interventional cardiac procedure

The International Commission on Radiological Protection reviewed its recommendation concerning the equivalent dose limit for the dose limits for occupationally exposed persons in a year. This limit was approved and written down in the IAEA (International Atomic Energy Agency) BSS (Basic Safety Standard) of July 2014. For that reason, in this work scattered radiation from fluoroscopy X-ray equipment on eye lens, and whole body dose was determined. For scattered radiation dose determination were used thermoluminescent dosimeter consisted of lithium fluoride doped with magnesium and titanium (LiF:Mg,Ti). 52 interventional cardiology procedures were analyzed and were categorized into two groups depending on the nature of procedure, diagnostic coronary angiography (CA) and percutaneous coronary interventions (PCI). The effective dose on the primary operator (O1) was in the range from 0.97 up to 3.02 μSv in the right side, meanwhile in the left side was in the range from 0.95 up to 12.44 μSv per each procedure. In regard to protection, the associated levels were found higher for one of the cardiologist, corrective action was suggested, ALARA concepts for all cardiologist was recommended for its implementation.

Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy

IntroductionPost-treatment lymphocytopaenia is a recognized complication of thoracic radiotherapy likely due to irradiation of a large volume of circulatory blood. We hypothesize that post-treatment absolute lymphocyte count (ALC) is associated with integral body dose and overall survival (OS) in lung cancer patients treated with radical radiotherapy. Materials and methodsData on clinicopathological variables, dosimetric parameters, and pre and post-treatment blood counts were collected retrospectively in 217 lung cancer patients (131 with non-small cell lung cancer and 86 with small cell lung cancer) treated with radical radiotherapy. Induction chemotherapy followed by radiotherapy and concurrent chemoradiotherapy were delivered in 89 (42%) and 99 (47%) patients respectively. Multiple stepwise regression analysis was performed separately for ALC and absolute neutrophil count (ANC) to derive a model for prediction of post-treatment count and multivariate analysis was performed for OS using a Cox regression model. ResultsThere was a significant decline in post-treatment counts for both ANC and ALC (p < 0.001). Multiple stepwise linear regression analysis confirmed pre-treatment ALC, body integral dose and use of concurrent chemotherapy as significant predictors of post-treatment ALC (R2 = 0.33, F(4,212) = 26.6 p < 0.001). Pre-treatment ANC, integral heart dose and number of fractions were significant predictors of post-treatment ANC (R2 = 0.18, F(3,213) = 16.38 p < 0.001). Low post-treatment ALC, high pre-treatment ANC, high planning target volume integral dose and lower number of fractions were predictive of inferior OS. ConclusionsThere is a negative correlation between integral body dose and post-treatment ALC which is an adverse prognostic factor in lung cancer patients treated with radical radiotherapy.

Alpha-Particle Therapy for Acute Myeloid Leukemia

Early studies using the humanized anti-CD33 monoclonal antibody lintuzumab labeled with β-emitters showed significant activity against acute myeloid leukemia (AML) but produced prolonged myelosuppression necessitating hematopoietic cell transplantation (HCT). Targeted α-particle therapy may produce more efficient tumor killing while sparing normal cells. An initial phase I trial of bismuth-213 (213Bi)-lintuzumab in relapsed and refractory (R/R) AML provided proof-of-principle for systemically administered α-particle therapy (Jurcic, Blood 2002). 213Bi-lintuzumab demonstrated rapid targeting of disease sites without significant extramedullary toxicity. Target-to-whole body dose ratios were greatly enhanced compared to β-emitting immunoconjugates. Anti-leukemic effects were seen across all dose levels with a decrease in marrow blasts in 78% of patients. In a subsequent phase I/II trial, 213Bilintuzumab was administered following partial cytoreduction with cytarabine (Rosenblat, Clin Cancer Res 2010). Among patients receiving the maximum tolerated dose of 37 MBq/kg or higher, responses were seen in 24% of patients. The 46-minute half-life of 213Bi, however, remained an obstacle to its widespread use. Therefore, a more potent second-generation construct containing actinium-225 (225Ac) (t½ = 10 days), which generates four α-particle emissions, was developed. A phase I study demonstrated that a single dose of 225Aclintuzuamb was safe at doses of 111 kBq/kg or less and produced marrow blast reductions in 67% of evaluable patients with R/R AML (Jurcic, ASH 2011). Dose-limiting toxicity was prolonged myelosuppression, and no evidence of radiation-induced nephrotoxicity was seen. Based on these findings, 225Ac-lintuzumab was investigated in a multicenter phase I/II trial in combination with low-dose cytarabine for older patients with untreated AML (Jurcic, SNMMI 2017). During the first cycle of therapy, two fractions of 225Ac-lintuzumab (18.5-74 kBq/kg/fraction) were administered one week apart after completion of chemotherapy. Five of 18 patients (28%) had objective responses. All responses occurred after the first cycle. The baseline peripheral blood blast count was a strong predictor of outcome, as responses were seen only in patients with peripheral blast counts < 200/μL. This is most likely explained by preferential antibody binding to peripheral sites in patients with higher circulating blast counts, leading to decreased marrow targeting. Because of this observation, a multicenter phase II trial of 225Ac-lintuzumab monotherapy using hydroxyurea to lower peripheral blast counts if needed was undertaken in older AML patients (Finn, ASH 2017). Objective responses were seen in nine of 13 patients (69%) after two doses of 225Ac-lintuzumab (74 kBq/kg) administered one week apart. Myelosuppression, however, was considered to be longer than acceptable in this population, and additional patients were treated with two fractions of 55.5 kBq/kg each. 225Ac-lintuzumab has shown significant activity in AML both alone and in combination with chemotherapy. Future development of 225Ac-lintuzumab includes combinations with standard chemotherapy and novel targeted agents for R/R AML, treatment for measurable residual disease in AML, and conditioning before HCT in patients with high-risk myelodysplastic syndromes.

Comparison between Al2O3:C pellets and DIODEs for TSEB in vivo dosimetry using an anthropomorphic phantom

The Total Skin Electron Beam (TSEB) therapy is a technique that aims to provide skin surface homogeneous absorbed dose in order to treat cutaneous T-cell lymphomas, both for curative and palliative purposes with electron beams penetrating a few millimeters into the skin, reaching the affected parts without affecting internal organs. In vivo dosimetry has become an important role for the treatment of total skin irradiation within a rigorous quality assurance. The luminescent dosimeters, such as TLDs and OSLDs, have proven to be very useful for the verification of the dose distribution and prescribed for the patient as the dose may differ from place to place due to patient body geometry, overlapping of structures and asymmetries of the radiation field. Other routine in vivo dosimetry tool is the DIODEs and they as well help validating radiation therapy dosimetry. Al2O3:C OSL pellets manufactured and marketed by REXON Components and TLD Systems have already been characterized for TSEB applications. The aim of this work is to compare the performance of Al2O3:C OSL pellets from REXON to in vivo TSEB dosimetry with silicon DIODEs QEDTM detectors from Sun Nuclear (EUA) using an anthropometric phantom. Dosimeters and DIODEs were previously characterized for 6 MeV HDTSe- electron beams and then placed over an Anderson Rando® anthropomorphic phantom, evaluating the body dose distribution. The reference point of measurement was the umbiculous as recommended by formalism. The results showed that the Al2O3:C OSL pellets presented acceptable results, but some greater variation of the response in relation to silicon DIODEs were found due to its considerable rotational dependency.

HOW TO ESTABLISH AN ADEQUATE SYSTEM FOR EYE LENS DOSE MONITORING: A PROPOSAL FOR TYPICAL WORKPLACES.

For years, the dose limit of 150 mSv for occupational exposure of the lens of the eye to ionising radiation was rarely exceeded, and the dose to the eye was only monitored occasionally. With the national implementation of the European Basic Safety Standards in 2018, this dose limit was reduced to 20 mSv and the Member States are expected to implement an adequate system for the monitoring of category A workers. Where the system for monitoring the whole body dose is settled in most countries, this is not the situation for the lens of the eye. This article presents a system for eye lens dose monitoring, based on the particle type, energy, angle of incidence and geometry of the radiation field and the use of protective measures. The system provides recommendations for the adequate operational quantity and dosemeter position for some of the most relevant workplaces.

Distinct vascular genomic response of proton and gamma radiation-A pilot investigation.

The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge. We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5–200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response. While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes; q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation; p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships. Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

Exposure duration and absorbed dose assessment in pesticide-exposed agricultural workers: Implications for risk assessment and modeling.

Absorbed dose assessment from dermal exposure involves multiplying skin contamination by the dermal absorption coefficient, which is usually defined for the standard workday of 8 h. This strategy may suffer from limitations when the duration of exposure is extremely variable, such as in agricultural exposure to pesticides. The aim of this study was to estimate the dose of mancozeb absorbed by agricultural pesticide applicators in a typical working day considering the real duration of exposure, to compare these estimates with those coming from the use of the Fixed Fractional Approach, and to assess the suitability of the dose estimates in the interpretation of biological monitoring results. In a series of real-life field studies on 29 workers applying mancozeb in vineyards for 38 work days, three sets of data were collected: information regarding work activities for each work day, potential (on clothes) and actual skin exposure using the "patch" methodology, and excretion of ethylenethiourea (ETU) in the 24-h pre-exposure and 24-h post-exposure urine samples. The statistical analyses were done using the R Language and Environment for Statistical Computing. Accounting for the duration of exposure led to a substantial reduction in the absorbed dose estimates, compared to the estimates coming from the Fixed Fractional Approach. In particular, absorbed dose by the body, hands' and total absorbed dose were reduced by 50%, 81%, and 80% respectively. The body dose estimated considering both approaches still correlated better with post-exposure 24-h urine ETU levels than the hands' dose, although more than 90% of the estimated total absorbed dose comes from the hands. An accurate estimate of the absorbed dose, carried out considering the real duration of exposure, can result in a higher correlation with a biomarker of occupational exposure, such as urine ETU, or at least yield more accurate results. This can facilitate the interpretation of biological monitoring data in pesticide-exposed agricultural workers despite the absence of biological exposure limits. ETU should be evaluated as a potentially relevant source of exposure due to ethylenebisdithiocarbamates' (EBDCs) degradation in the formulated product or spray mixture.

Monte Carlo simulation of whole body dose distribution in patients with total body X (γ) ray irradiation

Objective To explore the feasibility of application of the Monte Carlo method to simulate the whole body dose distribution in patients with total body X (γ) ray irradiation by comparing the actual measurement results. Methods A Monte Carlo model of a 6 MV Elekta Synergy Clinical linear accelerator was established by MCNPX. According to the relationship between the CT value and the density of the material, the CT of the ATOM physical phantom was converted into a voxel phantom for MCNPX calculation. The dose distribution of the whole body was simulated in the total body X (γ) ray irradiation. The simulated results were compared with the measurement values of the thermoluminescence dosimetry at different positions in the ATOM physical phantom to analyze the differences. Results The difference between the depth dose curve and the off-axis dose curve and the actual measurement values calculated by the 6 MV accelerator treatment head model in the water tank was less than 2%, with the maximum dose depth of approximately 1.5 cm and field size of 10 cm×10 cm, which were consistent with the actual measurement values. The maximum difference between the simulated results at different locations in the body and the thermoluminescence dosimeter was approximately 4%, and the simulated results of MCNPX were almost in good agreement with the results of thermoluminescence. Conclusions The whole body dose distribution in patient with total body X (γ) ray irradiation can be accurately simulated by MCNPX. Monte Carlo simulation makes it possible to optimize the uniformity of the total body dose during the total body irradiation process. Key words: Total body irradiation; Monte Carlo simulation; Dose uniformity; Thermoluminescence dosimetry

OVERTREATMENT AND HYPOGLYCEMIA PREVALENCE IN GERIATRIC PATIENTS WITH TYPE-2 DIABETES IN THE TURKISH POPULATION.

To determine the prevalence of over-treatment and hypoglycemia in Turkish type-2 diabetes patients and to identify the risk factors. Patients ≥ 65 years, having a minimum 5 years of type-2 diabetes, were included in the study. Patients' body mass index, mean HbA1c level, disease onset and medications related with their co-morbidities were recorded. Over-treatment is defined as the use of non-metformin therapies despite having HbA1c levels < 7%. A history of hypoglycemia episodes in the last three months and patients' home blood glucose measurements were recorded. Factors relating to hypoglycemia and over-treatment were analyzed. After applying criteria, 755 patients were included in the study: 728 patients (96.4%) had at least one comorbidity. 257 patients (34%) were found to have HbA1c levels < 7%. 217 of them (84.4%) were using non-metformin therapies. 497 patients (65.8%) were using insulin. The over-treatment prevalence in the ≥ 65 years group was 28.7%. The over-treatment ratio in ≥ 80 years group was 28.2%. Hypoglycemia prevalence in the last three months was 23.3%. It was 22.7% for patients ≥ 80 years. Mean age, disease duration, body mass index, insulin usage and doses were found to be significantly different in over-treated patients compared to the others. This study showed that despite recent guidelines, there is still a considerable amount of over-treated geriatric patients who are at risk of hypoglycemia and related morbidity and mortality. Insulinization rate was high. Physicians should not avoid de-intensifying the treatment of geriatric patients who have multiple co-morbidities.

MCDNet – A Denoising Convolutional Neural Network to Accelerate Monte Carlo Radiation Transport Simulations: A Proof of Principle With Patient Dose From X-Ray CT Imaging

X-ray computed tomography (CT) is a popular diagnostic imaging tool that has caused public concern over potential radiation risks to the patient. Monte Carlo (MC) simulations are the most accurate methods to calculate x-ray interactions with the patient's body and voxel-wise dose distributions, but the statistical methods suffer from extremely long computing time that is required to achieve necessary statistical precision. In this paper, we propose and demonstrate the Monte Carlo Denoising Net (MCDNet), a convolutional encoder-decoder neural network, for the purpose of accelerating the MC radiation transport simulations for patient CT dosimetry. A unique set of full-body anatomically realistic adult voxel phantoms of various sizes and a GPU-based parallel MC code were used to produce adequate training and testing data for supervised learning. Gamma index passing rate (GIPR) was used to evaluate the performance of predicted dose maps. For CT scan protocols considered in this study, MCDNet is found to have the ability of predicting dose maps of $9.9\times 10 ^{\mathbf {7}}$ photons from corresponding dose maps of $1.3\times 10^{\mathbf {6}}$ photons, yielding $76\times $ speed-up in terms of photon numbers used in the MC simulations. MCDNet is the first CNN-based method to speed-up MC radiation transport simulations involving 3D and heterogeneous patient anatomies for x-ray CT. Future studies will test the feasibility of applying the deep-learning based denoising strategy to other MC radiation transport applications.

Preclinical study for antitumor mechanism of lenvatinib and clinical studies for hepatocellular carcinoma

Lenvatinib is an oral multikinase inhibitor that targets VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT. The preclinical studies of lenvatinib for hepatocellular carcinoma (HCC) suggest that lenvatinib exerts the potent antitumor effect on the basis of the inhibitory actions on VEGF and FGF-induced tumor angiogenesis and on FGF-induced tumor cell growth. Phase I and II trials were conducted in Japan and Korea evaluating the maximal tolerated dose, efficacy, and safety of lenvatinib for HCC patients and have produced promising results. Considering the relationship between body weight, AUC and dose in HCC patients, the recommended starting dose was determined to be 8 mg/day for patients weighing lower than 60 kg and 12 mg/day for patients of 60 kg and higher. A phase III REFLECT study have demonstrated that the non-inferiority of lenvatinib to sorafenib in overall survival was confirmed and that lenvatinib was significantly superior to sorafenib in the analysis of progression-free survival and response rate. Based on these results, lenvatinib has been approved for the treatment of patients with unresectable HCC in Japan, US, EU and others this year. Clinical studies of lenvatinib combination therapy with transarterial chemoembolization (TACE) and with immune checkpoint inhibitors are currently on-going. Because of the potent antitumor effect, lenvatinib may change treatment strategy for HCC patients in the future.

Radioactive Iodine Therapy in Patients with Differentiated Thyroid Cancer: Study of External Dose Rate Attenuation Law and Individualized Patient Management.

Therapy with radioactive iodine (131I) is a well established treatment method for postsurgical differentiated thyroid carcinoma (DTC). A fixed discharge time is generally set, regardless of individual differences in residual body radioactivity (RBA). This study aimed to investigate the RBA of each patient to find the attenuation law and to identify underlying factors in order to predict the time point for a safe, scientifically sound discharge plan. A total of 231 DTC patients undergoing 131I treatment were all treated with 3.7 GBq (100 mCi) of 131I. RBA was estimated by measuring the external body dose rate (EDR) at a distance of 1 m from the body surface between 0 and 72 hours after oral administration of 131I. Data from each patient were used to establish a time-EDR value (h-μSv/h) curve. Software was developed to predict the time when a patient's dose equivalent meets the national safety standard by including six time points between 40 and 60 hours. Several factors that might affect that time were analyzed. The EDR attenuation law in patients could be described with a double exponential decay model, and the cutoff value was set as 23.3 μSv/h, upon which the predictive software was developed. Student's t-test showed there was no statistical difference between predicted values and the actual measured values (p > 0.05). Correlation analysis found that serum thyroglobulin, total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine, thyrotropin, 2- and 24-hour iodine uptake rate of the thyroid, scores of 99mTc-pertechnetate thyroid scan, scores of 131I whole-body scan, scores of ultrasound scan, and gastrointestinal residues were associated with attenuation speed. A further multiple linear regression analysis found that 24-hour iodine uptake (X1), residual thyroid grading by 131I whole-body scan (X2), blood free triiodothyronine (X3) and free thyroxine (X4) predominantly influenced the decline of the EDR. The regression equation was Ŷ = 2.091X1 + 6.370X2 + 4.529X3 + 2.466X4 - 8.614 (F = 44.03, p < 0.01). An effective and convenient method was created to measure and predict the individual safety time for discharge. This could play a significant role not only for scientific hospital discharge planning, rational use of medical resources, and better individualized management, but also in public radiation protection.

Assessment of secondary neutron dose due to dental restorations in head and neck radiation therapy

Introduction: One of scientific concern is increasing of unwanted neutron dose to the patient, in head and neck radiation therapy due to the presence of some isotopes in dental restorations and head of medical linac. The aim of this study is to measure the equivalent dose of thermal and fast neutron due to head of Siemens Primus Linac and a healthy tooth, Amalgam, Ni-Cr alloy and Ceramco irradiated by 15 MV photon beams. Materials and Methods: To evaluation of production of secondary neutrons due to the various dental restorations and head of medical linac in in 15 MV photon beam of Siemens Primus linac (Siemens AG, Erlangen, Germany), three commercial dental materials were used. This dental phantom configuration was consisted of combination of two healthy teeth, a tooth filled with Amalgam, a Ni-Cr alloy and Ceramco which they were collected randomly from dentistry clinics. The dental phantom was placed in depth of 1 cm in PMMA. In order to score of thermal and fast neutron equivalent doses, CR-39 detector was used. All the results of equivalent dose are considered to the delivery of 100 cGy dose at the maximum depth of 3.1 cm in the PMMA phantom with 15 MV photon beam and 10 × 10 cm2 field. Results: It is found out the maximum fast neutron dose was scored on the phantom surface which is related to head of Siemens primus linac. About the dental restorations, maximum fast neutron equivalent dose is related to amalgam, Ceramco and Ni-Cr alloy with amount of 0.19 mSv, 1.04 mSv, and 0.97 mSv at depth of 1.8 cm, respectively and then they decrease as the depth increases. The minimum amount of thermal neutron dose was measured on the surface of phantom. In case of denture samples, after dental phantom, the trend of the thermal neutron dose is reduced. The results indicated that maximum amount of thermal equivalent dose is related to Amalgam, Ceramco and Ni-Cr alloy and is equal to 1.45 mSv, 1.38 mSv, and 1.32 mSv, respectively. Conclusion: This study indicates an interpretation about photoneutron production in presence of the various dental restorations and head of Siemens primus medical linac. Presence of some elements in metallic dentures and head of medical linac, on the path of high photon beam can leads to the additional dose in the patient body. According to these results, thermal and fast neutron equivalent dose are started with an increase then they are reduced at depths after the dental restorations. Therefore, according to these results, it is recommended that some attempt should be carried out to make sure that the dental restorations are not in the path of primary photon beam with high energy.