PET/CT-based deep learning grading signature to optimize surgical decisions for clinical stage I invasive lung adenocarcinoma and biologic basis under its prediction: a multicenter study.

PURPOSE: No consensus on a grading system for invasive lung adenocarcinoma had been built over a long period of time. Until October 2020, a novel grading system was proposed to quantify the whole landscape of histologic subtypes and proportions of pulmonary adenocarcinomas. This study aims to develop a deep learning grading signature (DLGS) based on positron emission tomography/computed tomography (PET/CT) to personalize surgical treatments for clinical stage I invasive lung adenocarcinoma and explore the biologic basis under its prediction. METHODS: A total of 2638 patients with clinical stage I invasive lung adenocarcinoma from 4 medical centers were retrospectively included to construct and validate the DLGS. The predictive performance of the DLGS was evaluated by the area under the receiver operating characteristic curve (AUC), its potential to optimize surgical treatments was investigated via survival analyses in risk groups defined by the DLGS, and its biological basis was explored by comparing histologic patterns, genotypic alternations, genetic pathways, and infiltration of immune cells in microenvironments between risk groups. RESULTS: The DLGS to predict grade 3 achieved AUCs of 0.862, 0.844, and 0.851 in the validation set (n = 497), external cohort (n = 382), and prospective cohort (n = 600), respectively, which were significantly better than 0.814, 0.810, and 0.806 of the PET model, 0.813, 0.795, and 0.824 of the CT model, and 0.762, 0.734, and 0.751 of the clinical model. Additionally, for DLGS-defined high-risk population, lobectomy yielded an improved prognosis compared to sublobectomy p = 0.085 for overall survival [OS] and p = 0.038 for recurrence-free survival [RFS]) and systematic nodal dissection conferred a superior prognosis to limited nodal dissection (p = 0.001 for OS and p = 0.041 for RFS). CONCLUSION: The DLGS harbors the potential to predict the histologic grade and personalize the surgical treatments for clinical stage I invasive lung adenocarcinoma. Its applicability to other territories should be further validated by a larger international study.

Intravenous insulin preparation administration for myocardial viability 18F-FDG imaging has the potential to reduce radiation exposure dose.

OBJECTIVE: Fluorine-18-fluorodeoxyglucose (18F-FDG) injection activity is positively associated with radiation dose and positron emission tomography (PET) image count. Measurement error is greater with smaller counts; therefore, precise analysis is needed to avoid high doses of radiation exposure caused by high 18F-FDG injection. We aimed to identify and validate the optimal 18F-FDG injection activity and acquisition time for cardiac viability imaging with intravenous insulin preparation administration based on fixed 18F-FDG activity. MATERIALS AND METHODS: Cardiac PET images from 30 patients with coronary artery disease (CAD) were retrospectively reconstructed into different durations. An optimal product of the maximum standardized uptake value (SUV) of the myocardium, and segmental uptake (SU), and acquisition time (MSAT) was determined through a receiver operating characteristic curve. RESULTS: The optimal acquisition time (OAT) was equal to MSAT divided by mean SUV of the myocardium (MyoSUV) and was validated in another 26 patients with CAD. The optimal MSAT was 848.2s. In the validation group, the OAT was 129±76s (95% confidence interval, 99-160s), approximately one-third of the usual acquisition time. The MyoSUV and SU were equivalent between PET image duration of OAT and 600s (7.71±3.01 vs. 7.56±2.94; 67.1±15.4% vs. 67.7±15.6%). CONCLUSION: Intravenous insulin preparation administration has the potential to decrease the radiation exposure or acquisition time in cardiac viability 18F-FDG imaging to one-third, without losing the accurate measurement of MyoSUV or SU when reaching an OAT.

Elevated standardised uptake value of the free wall of the right ventricular myocardium is correlated with enlarged left ventricular end-diastolic volume among patients with heart failure with reduced ejection fraction: A retrospective study.

This study aimed to investigate the relationship between the standardised uptake value of the free wall of the right ventricular myocardium (SUVrv) and left ventricular end-diastolic volume (LVEDV) among patients with heart failure with reduced ejection fraction (HFrEF) with coronary artery disease (CAD). This retrospective study included 50 patients with CAD and HFrEF scheduled for cardiac viability imaging with electrocardiography-gated fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). The maximal SUVrv was measured. The LVEDV and left ventricular ejection fraction (LVEF) were automatically measured using quantitative gated single-photon emission computed tomography. Plasma brain natriuretic peptide (BNP) levels were obtained from medical records.The LVEF (0.24±0.06) was markedly reduced while the LVEDV (201.5±59.9mL) and BNP level (1348.1±1382.9pg/mL) were remarkably elevated. The SUVrv was 3.7±1.7 and was similar between patients with and without diabetes. The SUVrv was significantly positively correlated with the LVEDV and BNP level (r=0.35, 0.45; P=0.01, ≤0.01, respectively) but was unrelated to the LVEF (r=0.11, P=0.44). Herein, SUVrv was elevated and significantly positively correlated with LVEDV and BNP levels among patients with CAD and HFrEF but was unrelated to LVEF and diabetic status.

Convergent perturbation of the human domain-resolved interactome by viruses and mutations inducing similar disease phenotypes.

An important goal of systems medicine is to study disease in the context of genetic and environmental perturbations to the human interactome network. For diseases with both genetic and infectious contributors, a key postulate is that similar perturbations of the human interactome by either disease mutations or pathogens can have similar disease consequences. This postulate has so far only been tested for a few viral species at the level of whole proteins. Here, we expand the scope of viral species examined, and test this postulate more rigorously at the higher resolution of protein domains. Focusing on diseases with both genetic and viral contributors, we found significant convergent perturbation of the human domain-resolved interactome by endogenous genetic mutations and exogenous viral proteins inducing similar disease phenotypes. Pan-cancer, pan-oncovirus analysis further revealed that domains of human oncoproteins either physically targeted or structurally mimicked by oncoviruses are enriched for cancer driver rather than passenger mutations, suggesting convergent targeting of cancer driver pathways by diverse oncoviruses. Our study provides a framework for high-resolution, network-based comparison of various disease factors, both genetic and environmental, in terms of their impacts on the human interactome.

Theoretical Analysis for Bending of Single-Stranded DNA Adsorption on Microcantilever Sensors.

An energy-based model is presented to establish the bending deformation of microcantilever beams induced by single-stranded DNA (ssDNA) adsorption. The total free energy of the DNA-microcantilever sensor was obtained by considering the excluded-volume energy and the polymer stretching energy of DNA chains from mean-field theory, and the mechanical energy of three non-biological layers. The radius of curvature and deflection of the cantilever were determined through the minimum principle of energy. The efficiency of the present model was confirmed through comparison with experimental data. The effects of length, grafting density, salt concentration, thickness, and elastic modulus of substrate on tip deflections are also discussed in this paper. These factors can significantly affect the deflections of the biosensor. This work demonstrates that it is useful to develop a theoretical model for the label-free nanomechanical detection technique.

Errors in the absorbed and the administered 131I therapeutic dose in patients with Graves' disease. A suggested more precise technique.

OBJECTIVE: The aim of this study was to evaluate the relative error (RE) in the thyroid absorbed dose (TD) of iodine-131 (131I) in patients with Graves' disease comparing the simplified Quimby-Marinelli-Hine formula method (sQMHF) and the Standard Operational Procedures for dosimetry (SOPD) recommended by the European Association of Nuclear Medicine. PATIENTS AND METHODS: This study included 45 patients with Graves' disease 12 men and 33 women; age 44.1±12.8 years. Thyroid mass (TM) was measured using ultrasound. Uptake of 131I (RAIU) was tested at 2, 4-6, 24, 48-72, and 96-168h after its administration and the half-life (T1/2eff) and resident time (RT) of 131I were computed. According to the sQMHF, a prescribed TD of 75Gy required 3.7MBq/g of 131I, correction based on the RAIU24h and T1/2eff. Subsequently, the therapeutic TD was computed according to the SOPD and the RE was recorded. The data were analyzed using t-tests. RESULTS: The TM, RAIU24h, therapeutic TD, and RE were 36.5±23.9g, 0.54±0.14, 89.4±9.4Gy, and -0.01±0.02, respectively. There was a significant difference (t-value 9.84, P<0.01) between the prescribed and therapeutic TD because the sQMHF ignores the absorbed dose deposited in the thyroid during the first 24h, which is included in the SOPD. In addition, the RE was significantly smaller than the variable coefficient (VC) of the therapeutic TD (t=-39.6, P<0.01). CONCLUSION: When the activity of 131I was calculated using the simplified Q-M-H formula, the therapeutic absorbed thyroid dose was significantly higher than what was expected for the prescribed dose. Precision of the individualized therapeutic absorbed dose could be improved by computing the activity of 131I using the standard operational procedures for dosimetry of the EANM.

Cytoplasmic mislocalization of p27 and CDK2 mediates the anti-migratory and anti-proliferative effects of Nodal in human trophoblast cells.

p27(Kip1), a cyclin-dependent kinase (CDK) inhibitor, is a multi-functional protein that regulates various cellular activities. Trophoblast proliferation, migration and invasion are some of the key processes of placental development. We have recently reported that Nodal, a member of the transforming growth factor-ß (TGF-ß) superfamily, inhibits human trophoblast cell proliferation, migration and invasion. In the present study, we investigated the mechanism by which Nodal regulates trophoblast activities. We found that Nodal increased p27 mRNA and protein levels by enhancing their stability. Interestingly, Nodal signaling also induced nuclear export of p27 and CDK2. Cytoplasmic translocation of p27 induced by Nodal requires p27 phosphorylation at S10. In addition, Nodal enhanced the association of p27 with CDK2, CDK5 and a microtubule-destabilizing protein, stathmin, and induced stathmin phosphorylation at S25 and S38. Furthermore, Nodal increased tubulin stability as revealed by immunofluorescent staining of acetylated tubulin. Finally, silencing of p27 reversed the inhibitory effect of Nodal on trophoblast cell proliferation, migration and invasion. Taken together, our findings revealed a novel function of simultaneous p27 and CDK2 cytoplasmic mislocalization in mediating growth-factor-regulated cell proliferation, migration and invasion.

Seronegative primary Sjögren's syndrome, a distinct subtype of primary Sjögren's syndrome in Chinese patients.

BACKGROUND: To investigate the clinical and immune characteristics of patients with primary Sjögren's syndrome (pSS) who were negative for anti-Sjögren's-syndrome-related antigen A antibodies (anti-SSA) and anti-Sjögren's-syndrome-related antigen B antibodies (anti-SSB) in Chinese population. METHODS: A retrospective study were performed and 232 patients with pSS were analyzed. Patients positive for anti-SSA or/and anti-SSB were termed as seropositive pSS, and these negative for both anti-SSA and anti-SSB (non-antinuclear antibodies) as seronegative pSS. Clinical manifestations and laboratory findings were compared between the two groups. RESULTS: Among the 232 patients with pSS, 192 (82.8%) were seropositive pSS and 40 (17.2%) were seronegative pSS. Compared to seropositive pSS, seronegative pSS were older and with higher percentage of low disease activity (ESSDAI < 5), xerostomia and xerophthalmia, with higher platelet count and level of creatine kinase. This subgroup was with lower levels of gamma globulin, immunoglobulin G, immunoglobulin A and autoantibodies including rheumatoid factor and antinuclear antibody in serum, and less immunoglobulin G deposition in labial gland. CONCLUSION: Seronegative pSS was a distinct subtype of pSS different from seropositive pSS. Clinical manifestations in seronegative pSS subgroup were restricted to exocrine gland and less B lymphocyte activation, while seropositive pSS were prone to present with systemic involvement and high disease activity. Specific underlying pathogenesis mechanisms and therapeutic strategies in this subgroup needed to be further studied.

[A study on the differential diagnosis of ciliated epithelial cells from Lophomonas blattarum in bronchoalveolar lavage fluid].

OBJECTIVE: To validate the authenticity of the cases diagnosed as pulmonary Lophomonas blattarum infection in literatures and Lophomonas blattarum as a kind of pathogen resulting in pulmonary infection. METHODS: From June 2012 to May 2013, mobile cells with cilia at the anterior end of the cells were observed in BALF from 6 patients with pulmonary disease in our hospital. Morphological feature and ultrastructure of the cells were further investigated by optical microscope and electron microscope to determine the type of the cells referring to literature-published photos of Lophomonas blattarum. Literatures about Lophomonas blattarum infection were searched with keyword Lophomonas blattarum from Wanfang Data, China National Knowledge Infrastructure (CNKI) and PubMed. Diagnostic methods and figures provided by the literature were carefully reviewed, and the accuracy of diagnosis of pulmonary Lophomonas blattarum was identified. RESULTS: Mobile cells found in BALF from the 6 patients in our hospital had the morphological features of bronchial ciliate epithelial cells. A nucleus far from the cilia was observed in the middle or at the bottom of the cytoplasm, and these cells did not display the characteristic cytological structures of Lophomonas blattarum: calyx, perinuclear tubules and axial filament. Diagnosis of pulmonary Lophomonas blattarum reported in literatures so far were all based on the morphological features of mobile cells with a cluster of flagellate at anterior end of the cell by optical microscopy. None of the authors did further exploration on the ultrastructure of such a kind of cells and compared with features of Lophomonas blattarum described in the literature. All the active cells reported in literatures had the identical morphological features to those found in our investigation. CONCLUSION: In the past 20 years, all the diagnosed cases as pulmonary Lophomonas blattarum infection reported in our country were misdiagnosed. Currently, there is no evidence to show Lophomonas blattarum as a pathogen resulting in pulmonary infection.

PET/CT based cross-modal deep learning signature to predict occult nodal metastasis in lung cancer.

Occult nodal metastasis (ONM) plays a significant role in comprehensive treatments of non-small cell lung cancer (NSCLC). This study aims to develop a deep learning signature based on positron emission tomography/computed tomography to predict ONM of clinical stage N0 NSCLC. An internal cohort (n = 1911) is included to construct the deep learning nodal metastasis signature (DLNMS). Subsequently, an external cohort (n = 355) and a prospective cohort (n = 999) are utilized to fully validate the predictive performances of the DLNMS. Here, we show areas under the receiver operating characteristic curve of the DLNMS for occult N1 prediction are 0.958, 0.879 and 0.914 in the validation set, external cohort and prospective cohort, respectively, and for occult N2 prediction are 0.942, 0.875 and 0.919, respectively, which are significantly better than the single-modal deep learning models, clinical model and physicians. This study demonstrates that the DLNMS harbors the potential to predict ONM of clinical stage N0 NSCLC.

Shock-induced plasticity and phase transformation in single crystal magnesium: an interatomic potential and non-equilibrium molecular dynamics simulations.

An effective and reliable Finnis-Sinclair (FS) type potential is developed for large-scale molecular dynamics (MD) simulations of plasticity and phase transition of magnesium (Mg) single crystals under high-pressure shock loading. The shock-wave profiles exhibit a split elastic-inelastic wave in the [0001]HCPshock orientation and a three-wave structure in the [10-10]HCPand [-12-10]HCPdirections, namely, an elastic precursor, a followed plastic front, and a phase-transition front. The shock Hugoniot of the particle velocity (Up) vs the shock velocity (Us) of Mg single crystals in three shock directions under low shock strength reveals apparent anisotropy, which vanishes with increasing shock strength. For the [0001]HCPshock direction, the amorphization caused by strong atomic strain plays an important role in the phase transition and allows for the phase transition from an isotropic stressed state to the product phase. The reorientation in the shock directions [10-10]HCPand [-12-10]HCP, as the primary plasticity deformation, leads to the compressed hexagonal close-packed (HCP) phase and reduces the phase-transition threshold pressure. The phase-transition pathway in the shock direction [0001]HCPincludes a preferential contraction strain along the [0001]HCPdirection, a tension along [-12-10]HCPdirection, an effective contraction and shear along the [10-10]HCPdirection. For the [10-10]HCPand [-12-10]HCPshock directions, the phase-transition pathway consists of two steps: a reorientation and the subsequent transition from the reorientation hexagonal close-packed phase (RHCP) to the body-centered cubic (BCC). The orientation relationships between HCP and BCC are (0001)HCP⟨-12-10⟩HCP// {110}BCC⟨001⟩BCC. Due to different slipping directions during the phase transition, three variants of the product phase are observed in the shocked samples, accompanied by three kinds of typical coherent twin-grain boundaries between the variants. The results indicate that the highly concentrated shear stress leads to the crystal lattice instability in the elastic precursor, and the plasticity or the phase transition relaxed the shear stress.

miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis.

We tried to unveil the clinical significance of miR-146a as a biomarker in M2 macrophage polarization in diabetic wound healing. Initially, we found reduced miR-146a in macrophages of diabetic patients. Next, dual-luciferase assay verified that toll-like receptor 4 (TLR4) was a target gene of miR-146 and was negatively regulated by miR-146. Moreover, after ectopic expression and depletion experiments of miR-146 and/or TLR4, lipopolysaccharide-induced inflammatory response of macrophages was detected. The results revealed that overexpression of miR-146a promoted the M2 macrophage polarization by suppressing the TLR4/nuclear factor-kappaB (NF-κB) axis, so as to enhance wound healing in diabetic ulcers. Further, mouse models with diabetic ulcers were established to investigate the effects of miR-146a on diabetic wound healing in vivo, which revealed that miR-146a promoted wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. In conclusion, we demonstrate that miR-146a can induce M2 macrophage polarization to enhance wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis.

Development of a semi-empirical interatomic potential appropriate for the radiation defects in V-Ti-Ta-Nb high-entropy alloy.

High-entropy alloys (HEAs) hold promise as candidate structural materials in future nuclear energy systems. Body-centred cubic V-Ti-Ta-Nb HEAs have received extensive attention due to their excellent mechanical properties. In this work, the Finnis-Sinclair interatomic potential for quaternary V-Ti-Ta-Nb HEAs has been fitted based on the defect properties obtained with the density functional theory (DFT) calculations. The new potential for Nb accurately reproduces the vacancy formation energy, vacancy migration energy and interstitial formation energy. The typical radiation defect properties predicted by the alloy potential were consistent with the DFT results, including the binding energies between substitutional solute atoms, the binding energy between substitutional atoms and vacancies, and the formation energy of interstitial solute atoms. In addition, the mixing enthalpies of the alloys were also consistent with the DFT results. The present potential can also describe reasonably the collision cascade process of quaternary V-Ti-Ta-Nb HEAs.

Structural Profiling of Bacterial Effectors Reveals Enrichment of Host-Interacting Domains and Motifs.

Effector proteins are bacterial virulence factors secreted directly into host cells and, through extensive interactions with host proteins, rewire host signaling pathways to the advantage of the pathogen. Despite the crucial role of globular domains as mediators of protein-protein interactions (PPIs), previous structural studies of bacterial effectors are primarily focused on individual domains, rather than domain-mediated PPIs, which limits their ability to uncover systems-level molecular recognition principles governing host-bacteria interactions. Here, we took an interaction-centric approach and systematically examined the potential of structural components within bacterial proteins to engage in or target eukaryote-specific domain-domain interactions (DDIs). Our results indicate that: 1) effectors are about six times as likely as non-effectors to contain host-like domains that mediate DDIs exclusively in eukaryotes; 2) the average domain in effectors is about seven times as likely as that in non-effectors to co-occur with DDI partners in eukaryotes rather than in bacteria; and 3) effectors are about nine times as likely as non-effectors to contain bacteria-exclusive domains that target host domains mediating DDIs exclusively in eukaryotes. Moreover, in the absence of host-like domains or among pathogen proteins without domain assignment, effectors harbor a higher variety and density of short linear motifs targeting host domains that mediate DDIs exclusively in eukaryotes. Our study lends novel quantitative insight into the structural basis of effector-induced perturbation of host-endogenous PPIs and may aid in the design of selective inhibitors of host-pathogen interactions.

68Ga-DOTA-FAPI-04 PET/CT in Erdheim-Chester Disease.

ABSTRACT: A 56-year-old woman presented with edema in the upper part of the body, enlarged axillary lymph nodes, and progressive bone pain for 1 year. Malignant disease was initially suspected. This patient underwent 68Ga-DOTA-FAPI-04 PET/CT for detection of the primary lesion and evaluation of disease extent. 68Ga-DOTA-FAPI-04 PET/CT revealed multiple abnormal foci at the skeleton, muscle, lymph nodes, and subcutaneous fat. The imaging findings, highly suggestive of Erdheim-Chester disease, have been later confirmed by histopathology. This case highlights that 68Ga-DOTA-FAPI-04 PET/CT would be useful for evaluating the disease extent, guiding biopsies, and gauging the treatment response in patients with Erdheim-Chester disease.

Mechanism of Isosorbide Dinitrate Combined with Exercise Training Rehabilitation to Mobilize Endothelial Progenitor Cells in Patients with Coronary Heart Disease.

it was to explore effect of isosorbide dinitrate combined with exercise training and rehabilitation on endothelial progenitor cells (EPCs) in coronary heart disease. EPCs were isolated and cultured from peripheral blood of coronary heart disease patients, and morphology and surface markers were detected. Then, 116 patients were rolled into treatment group (isosorbide dinitrate + exercise rehabilitation training) and control group (isosorbide dinitrate). Characteristics of EPCs cells after treatment were compared. The mononuclear cells were round and small in size and were not evenly distributed in the culture plate. EPCs cells grew as colonies after 8d-culture, and the surrounding cells grew outward in a germinating manner with colonies as the center, forming multiple cell populations. Positive rates of EPCs surface markers CD133, CD34, and vascular endothelial growth factor receptor (KDR) were 11.25±3.07%, 48.18±9.13%, and 76.36±8.27%, respectively. Proliferation activity of EPCs in the treatment group was dramatically higher versus controls at day three, five, and seven (P<0.05). Adhesion ability of EPCs in treatment group was dramatically higher than controls at day three, five, and seven (P<0.05). Migration ability of EPCs in treatment group was dramatically higher versus control group at day three, five, and seven (P<0.05). In short, isosorbide dinitrate plus exercise rehabilitation greatly enhanced the proliferation activity, adhesion ability, and migration ability of EPCs cells, which also played a beneficial role in the repair of endothelial injury, with notable effects.

Characteristics of the Urinary Microbiome From Patients With Gout: A Prospective Study.

The role of host microbes in the pathogenesis of several diseases has been established, and altered microbiomes have been related to diseases. However, the variability of the urinary microbiome in individuals with gout has not been evaluated to date. Therefore, we conducted the present prospective study to characterize the urinary microbiome and its potential relation to gout. Urine samples from 30 patients with gout and 30 healthy controls were analyzed by Illumina MiSeq sequencing of the 16S rRNA hypervariable regions, and the microbiomes were compared according to alpha-diversity indices, complexity (beta diversity) with principal component analysis, and composition with linear discriminant analysis effect size. The most significantly different taxa at the phylum and genus levels were identified, and their potential as biomarkers for discriminating gout patients was assessed based on receiver operating characteristic (ROC) curve analysis. Compared with the healthy controls, there was a dramatic decrease in microbial richness and diversity in the urine of gout patients. The phylum Firmicutes and its derivatives (Lactobacillus_iners, Family_XI, and Finegoldia), the phylum Actinobacteria and its derivatives (unidentified_Actinobacteria, Corynebacteriales, Corynebacteriale, Corynebacterium_1, and Corynebacterium_tuberculostearicum), and the genera Prevotella and Corynebacterium_1 were significantly enriched in the urine of gout patients. ROC analysis indicated that the top five altered microbial genera could be reliable markers for distinguishing gout patients from healthy individuals. These findings demonstrate that there are specific alterations in the microbial diversity of gout patients. Thus, further studies on the causal relationship between gout and the urinary microbiome will offer new prospects for diagnosing, preventing, and treating gout.

Evaluation of the Efficacy of Standardized Uptake Value (SUV)-shape Scheme for Thyroid Volume Determination in Graves' Disease: A Comparison with Ultrasonography.

OBJECTIVES: In this study, we aimed to evaluate the efficacy of thyroid volume measurement using 99mTc pertechnetate single-photon emission computed tomography (SPECT) images, acquired by the standardized uptake value (SUV)-shape scheme designed by our expert team. METHODS: A total of 18 consecutive patients with Graves' disease (GD) were subjected to both ultrasonographic and 99mTc pertechnetate SPECT examinations of thyroid within a five-day interval. The volume of thyroid lobes and isthmus was measured by ultrasonography (US) according to the ellipsoid volume equation. The total thyroid volume, determined as the sum of the volume of both lobes and isthmus, was recorded as TV-US (i.e., thyroid volume measured by US) and set as the reference. The thyroid volume was defined according to our SUV-shape scheme and was recorded as TV-SS (i.e., thyroid volume determined by the SUV-shape scheme). The data were analyzed using the Bland-Altman plot, linear regression analysis, Spearman's rank correlation, and paired t-test, if necessary. RESULTS: The values of TV-SS (40.2±29.4 mL) and TV-US (43.0±34.7 mL) were not significantly different (t=0.813; P=0.43). The linear regression equation of the two values was determined as TV-US= 1.072 × TV-SS - 0.29 (r=0.906; P<0.01). CONCLUSION: The new scheme, i.e., SUV-shape scheme, exhibited potential for the measurement of thyroid volume in patients with GD.

Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer.

PURPOSE: Tumor necrosis treatment (TNT) uses degenerating tumor cells and necrotic regions of tumors as targets for radioimmunotherapy. Previous studies in animal tumor models and clinical trials have demonstrated that when linked to the therapeutic radionuclide iodine-131, recombinant chimeric TNT antibody ((131)I-chTNT) can deliver therapeutic doses to tumors regardless of the location or type of malignancy. Therapeutic efficacy and toxicity of (131)I-chTNT in advanced lung cancer patients were studied in this pivotal registration trial. PATIENTS AND METHODS: Patients with advanced lung cancer were treated with systemic or intratumoral injection of (131)I-chTNT in eight oncology centers in China. The objective response rate (ORR) was assessed as the primary end point. RESULTS: All 107 patients who were entered onto the study and completed therapy had experienced treatment failure after prior radiotherapy or chemotherapy a mean of three times. The results showed an ORR of 34.6% (complete response, 3.7%; partial response, 30.8%; no change, 55.1%; and progressive disease, 10.3%) in all patients and 33% in 97 non-small-cell lung cancer patients. A biodistribution study demonstrated excellent localization of the radioactivity in tumors in both systemically and intratumorally injected patients. The most obvious adverse side effect was mild and reversible bone marrow suppression. CONCLUSION: Radioimmunotherapy with (131)I-chTNT was well tolerated and can be used systemically or locally to treat refractory tumors of the lung.