[Retracted] Protective effect of microRNA­381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the certain of the cell proliferation assay data shown in Fig. 4C on p. 1444 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes, which had already been submitted for publication [Shi N, Shan B, Song Y, Chu H and Qian L: Circular RNA circ­PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR­3680­3p in esophageal squamous cell carcinoma. J Cell Biochem 120: 10021­10030, 2019]. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 21: 1439­1448, 2020; DOI: 10.3892/mmr.2020.10957].

Interobserver Variations in Target Delineation in Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma and its Impact on Target Dose Coverage.

BACKGROUND: To investigate the differences between physicians in target delineation in intensity-modulated radiation therapy for nasopharyngeal carcinoma as well as their impact on target dose coverage. METHODS: Ninety-nine in-hospital patients were randomly selected for retrospective analysis, and the target volumes were delineated by 2 physicians. The target volumes were integrated with the original plans, and the differential parameters, including the Dice similarity coefficient (DSC), Hausdorff distance (HD), and Jaccard similarity coefficient (JSC) were recorded. The dose-volume parameters to evaluate target dose coverage were analyzed by superimposing the same original plan to the 2 sets of images on which the target volumes were contoured by the 2 physicians. The significance of differences in target volumes and dose coverage were evaluated using statistical analysis. RESULTS: The target dose coverage for different sets of target volumes showed statistically significant differences, while the similarity metrics to evaluate geometric target volume differences did not. More specifically, for PGTVnx, the median DSC, JSC, and HD were 0.85, 0.74, and 11.73, respectively; for PCTV1, the median values were 0.87, 0.77, and 11.78, respectively; for PCTV2, the median values were 0.90, 0.82, and 16.12, respectively. For patients in stages T3-4, DSC, and JSC were reduced but HD was increased compared to those in stages T1-2. Dosimetric analysis indicated that, for the target volumes, significant differences between the 2 physicians were found in D95, D99, and V100 for all the target volumes (ie, PGTVnx, PCTV1, and PCTV2) across the whole group of patients, as well as in patients with disease stages T3-4 and T1-2. CONCLUSIONS: The target volumes delineated by the 2 physicians had a high similarity, but the maximal distances between the outer contours of the 2 sets were significantly different. In patients with advanced T stages, significant differences in dose distributions were found, stemming from the deviations of target delineation.

MLP-mmWP: High-Precision Millimeter Wave Positioning Based on MLP-Mixer Neural Networks.

Millimeter wave (MMW) communication, noted for its merit of wide bandwidth and high-speed transmission, is also a competitive implementation of the Internet of Everything (IoE). In an always-connected world, mutual data transmission and localization are the primary issues, such as the application of MMW application in autonomous vehicles and intelligent robots. Recently, artificial intelligence technologies have been adopted for the issues in the MMW communication domain. In this paper, MLP-mmWP, a deep learning method, is proposed to localize the user with respect to MMW communication information. The proposed method employs seven sequences of beamformed fingerprints (BFFs) to estimate localization, which includes line-of-sight (LOS) and non-line-of-sight (NLOS) transmissions. As far as we know, MLP-mmWP is the first method to apply the MLP-Mixer neural network to the task of MMW positioning. Moreover, experimental results in a public dataset demonstrate that MLP-mmWP outperforms the existing state-of-the-art methods. Specifically, in a simulation area of 400 × 400 m2, the positioning mean absolute error is 1.78 m, and the 95th percentile prediction error is 3.96 m, representing improvements of 11.8% and 8.2%, respectively.

Score test for missing at random or not under logistic missingness models.

Missing data are frequently encountered in various disciplines and can be divided into three categories: missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). Valid statistical approaches to missing data depend crucially on correct identification of the underlying missingness mechanism. Although the problem of testing whether this mechanism is MCAR or MAR has been extensively studied, there has been very little research on testing MAR versus MNAR. A critical challenge that is faced when dealing with this problem is the issue of model identification under MNAR. In this paper, under a logistic model for the missing probability, we develop two score tests for the problem of whether the missingness mechanism is MAR or MNAR under a parametric model and a semiparametric location model on the regression function. The implementation of the score tests circumvents the identification issue as it requires only parameter estimation under the null MAR assumption. Our simulations and analysis of human immunodeficiency virus data show that the score tests have well-controlled type I errors and desirable powers.

Metformin Can Be Safely Used in Patients Exposed to Contrast Media: A Systematic Review and Meta-Analysis.

BACKGROUND: There have been few studies published on the use of contrast media (CM) in metformin-treated patients. In this study, we conducted a systematic review and meta-analysis to investigate the relationship between metformin and contrast-induced acute kidney injury (CI-AKI). METHODS: A comprehensive search of the Medline, PubMed, Embase, and Web of Science databases for literature on associations between metformin use and CI-AKI incidence was conducted. The pooled odds ratio (OR), or relative risk, as well as the corresponding 95% confidence intervals (CIs), was calculated to assess the relationship between metformin and CI-AKI risk as well as the incidence of lactic acidosis (LA). RESULTS: In total, seven studies met our eligibility criteria on associations between metformin use and CI-AKI incidence, comprising 2,325 individuals, with 279 new cases of CI-AKI exposed to CM. The pooled analysis revealed no statistically significant increase in the risk of CI-AKI development in patients who used metformin continuously (random-effects OR: 1.15, 95% CI: 0.70-1.90, p = 0.57). No cases of LA that occurred during CM exposure were reported. CONCLUSION: Metformin can be safely used in patients with moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m2) during CM exposure.

The PLAUR signaling promotes chronic pruritus.

Chronic itch is a complex sensation of the skin frequently associated with skin diseases, such as atopic dermatitis (AD) and psoriasis. Although Serpin E1 is implicated in chronic itch, its receptor and signaling pathways involved in itch are not known. In this study, the clinical relevance of a putative Serpin E1 receptor PLAUR to chronic itch, and the neuro-cutaneous Serpin E1-PLAUR signaling are explored. We found that PLAUR is overexpressed in skin specimens of human lesional AD and lesional psoriasis, and sensory neurons innervating MC903-induced AD-like murine skin. Murine PLAUR+ sensory neurons responded to Serpin E1, resulting in enrichment of numerous itch- and inflammation-related genes and their protein release. PLAUR resides in TLR2+ neurons and Serpin E1 stimulus led to transcriptional upregulation of TLR2 and its co-signaling proteins. Agonists of TLR2 propagated itch-related gene transcription including BNP, OSM, and PAR2. OSM induced acute itch in mice and promoted G-CSF and IL-8 release from human keratinocytes. Serpin E1 inhibitor reduced MC903-induced itch, epidermal hyperplasia, immunocyte infiltration, and resulted in lower transcription/expression levels of Serpin E1 and OSM. Taken together, the PLAUR-TLR2-OSM signaling promotes skin-nerve communication, cutaneous inflammation, and itch, all feeding into an aggravation of AD and exaggerated itch circuits.

IL-20 promotes cutaneous inflammation and peripheral itch sensation in atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin disease, which is associated with intense itch, skin barrier dysfunction and eczematous lesions. Aberrant IL-20 expression has been implicated in numerous inflammatory diseases, including psoriasis. However, the role of IL-20 in AD remains unknown. Here, RNA-seq, Q-PCR, and immunocytochemistry were utilized to examine disease-driven changes of IL-20 and its cognate receptor subunits in skin from healthy human subjects, AD patients and murine AD-models. Calcium imaging, knockdown and cytokine array were used to investigate IL-20-evoked responses in keratinocytes and sensory neurons. The murine cheek model and behavioral scoring were employed to evaluate IL-20-elicited sensations in vivo. We found that transcripts and protein of IL-20 were upregulated in skin from human AD and murine AD-like models. Topical MC903 treatment in mice ear enhanced IL-20R1 expression in the trigeminal sensory ganglia, suggesting a lesion-associated and epidermal-driven mechanism for sensitization of sensory IL-20 signaling. IL-20 triggered calcium influx in both keratinocytes and sensory neurons, and promoted their AD-related molecule release and transcription of itch-related genes. In sensory neurons, IL-20 application increased TLR2 transcripts, implicating a link between innate immune response and IL-20. In a murine cheek model of acute itch, intradermal injection IL-20 and IL-13 elicited significant itch-like behavior, though only when co-injected. Our findings provide novel insights into IL-20 function in peripheral (skin-derived) itch and clinically relevant intercellular neuron-epidermal communication, highlighting a role of IL-20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL-20 epidermal pathways.

Expression profile, clinical significance and biological functions of IGF2BP2 in esophageal squamous cell carcinoma.

The ectopic expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been demonstrated to facilitate tumorigenesis and induce proliferation in a various types of cancer. However, the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) has yet been fully elucidated. In this regard, the current study assessed the expression patterns and clinical significance of IGF2BP2 in 94 Chinese patients diagnosed with ESCC. Immunohistochemistry and reverse transcription-quantitative PCR assays were employed to assess IGF2BP2 expression in ESCC tissues compared with adjacent healthy tissues. The results revealed that the protein expression of IGF2BP2 was substantially upregulated in ESCC tissues compared with adjacent ESCC tissues. More specifically, higher IGF2BP2 expression strongly associated with tumor node metastasis stage, lymphatic infiltration and lymph node metastasis. Using two ESCC cell lines (TE-1 and TE-10), the inhibition of IGF2BP2 expression by small interfering RNA was proven to induce apoptosis and suppress proliferation, migration and cell cycle progression in vitro. Collectively, the present findings indicated that IGF2BP2 may serve a major role in the development of ESCC carcinogenesis. The present study may be helpful in the design of potential drug targets in the treatment of ESCC.

Innate immune regulates cutaneous sensory IL-13 receptor alpha 2 to promote atopic dermatitis.

The clinical significance and regulators of IL-13Rα2 in itch and atopic dermatitis (AD) remain unclear. To identify disease-driven regulatory circuits of IL-13Rα2, transcriptomic/pathological analysis was performed in skin from patients with AD, psoriasis, healthy subjects, and murine AD model. Functionality was investigated in sensory neurons, keratinocytes and animal model, by using knockdown (KD), calcium imaging, RNA-seq, cytokine arrays, pharmacological assays, and behavioural investigations. In our study, an upregulated IL-13Rα2 expression was revealed in skin of AD patients, but not psoriasis, in a disease activity-dependent manner. In cultured human keratinocytes, IL-13 increased IL-13Rα2 transcription levels, and this were downregulated by IL-13Rα1KD. IL-13Rα2KD reduced transcription levels of EDNRA, CCL20, CCL26. In contrast, sensory neuron-derived IL-13Rα2 was upregulated by TLR2 heterodimer agonists, Pam3CSK4 and FSL-1. In a mouse cheek model, pre-administration of Pam3CSK4 and FSL-1 enhanced IL-13-elicited scratching behaviour. Consistently, in cultured sensory neurons Pam3CSK4 enhanced IL-13-elicted calcium transients, increased number of responders, and orchestrated chemerin, CCL17 and CCL22 release. These release was inhibited by IL-13Rα2KD. Collectively, IL-13 regulates keratinocyte-derived IL-13Rα2 and TLR2 to modulate neuronal IL-13Rα2, thereby promoting neurogenic inflammation and exacerbating AD and itch. Thus, the cutaneous IL-13-IL-13Rα2 and neuronal TLR2-IL-13Rα2 pathway represent important targets to treat AD and itch.

Cryptococcal endocarditis of native valves without immunodeficiency or drug abuse: a case report.

Cryptococcal endocarditis has rarely been reported. Most patients with this condition are associated with risk factors, such as structural heart disease/valve replacement, immunodeficiency/immunosuppression or drug abuse. We report a case of cryptococcal endocarditis of the native valves without any risk factors. A 50-year-old Chinese man was admitted to hospital with fever for 1 month without any underlying heart disease, immunodeficiency, or drug use. He was diagnosed as having Cryptococcus neoformans infective endocarditis and was discharged after valve replacement surgery and long-term antifungal therapy.

Detection of Theileria spp. in ticks, sheep keds (Melophagus ovinus), and livestock in the eastern Tibetan Plateau, China.

Theileria species, with a broad geographic distribution, infect a wide range of both domestic and wild animals and are transmitted by ixodid ticks. Currently, there is no comprehensive report regarding the distribution of Theileria spp. in the eastern Tibetan Plateau, especially in Ganze Tibetan autonomous prefecture (153,700 km2) and Ngawa Tibetan and Qiang autonomous prefecture (84,242 km2) of Sichuan province, China. In this study, we collected blood samples from yaks (n = 144) (Bos grunniens), Tibetan sheep (n = 92), and Tibet horses (n = 142) in Ganze and Ngawa.Theileria sinensis, T. luwenshuni, and T. equi were the dominant Theileria species detected in yaks, Tibetan sheep, and horses with the total infection rates of 25.7% (37/144), 75.0% (69/92), and 51.4% (73/142), respectively. For ectoparasites, T. luwenshuni was the only Theileria species detected in sheep keds (Melophagus ovinus) with an infection rate of 30.8% (8/26). The total infection rates of T. sinensis in Haemaphysalis qinghaiensis, Dermacentor everestianus, and Rhipicephalus microplus were 34.6% (36/104), 34.0% (17/50), and 51.3% (58/113), respectively. Theileria spp., belonging to T. sergenti/buffeli/orientalis group, were only detected in R. microplus collected in Danba county of Ganze with a total infection rate of 39.9% (19/48). Our results provide important data of the epidemiology of Theileria spp. in livestock and ectoparasites and will assist with the implementation of measures to control theileriosis transmission in eastern Tibetan Plateau, China.

Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease.

BACKGROUND & AIMS: There are few in vitro models for studying the 3-dimensional interactions among different liver cell types during organogenesis or disease development. We aimed to generate hepatic organoids that comprise different parenchymal liver cell types and have structural features of the liver, using human pluripotent stem cells. METHODS: We cultured H1 human embryonic stem cells (WA-01, passage 27-40) and induced pluripotent stem cells (GM23338) with a series of chemically defined and serum-free media to induce formation of posterior foregut cells, which were differentiated in 3 dimensions into hepatic endoderm spheroids and stepwise into hepatoblast spheroids. Hepatoblast spheroids were reseeded in a high-throughput format and induced to form hepatic organoids; development of functional bile canaliculi was imaged live. Levels of albumin and apolipoprotein B were measured in cell culture supernatants using an enzyme-linked immunosorbent assay. Levels of gamma glutamyl transferase and alkaline phosphatase were measured in cholangiocytes. Organoids were incubated with troglitazone for varying periods and bile transport and accumulation were visualized by live-imaging microscopy. Organoids were incubated with oleic and palmitic acid, and formation of lipid droplets was visualized by staining. We compared gene expression profiles of organoids incubated with free fatty acids or without. We also compared gene expression profiles between liver tissue samples from patients with nonalcoholic steatohepatitis (NASH) versus without. We quantified hepatocyte and cholangiocyte populations in organoids using immunostaining and flow cytometry; cholangiocyte proliferation of cholangiocytes was measured. We compared the bile canaliculi network in the organoids incubated with versus without free fatty acids by live imaging. RESULTS: Cells in organoids differentiated into hepatocytes and cholangiocytes, based on the expression of albumin and cytokeratin 7. Hepatocytes were functional, based on secretion of albumin and apolipoprotein B and cytochrome P450 activity; cholangiocytes were functional, based on gamma glutamyl transferase and alkaline phosphatase activity and proliferative responses to secretin. The organoids organized a functional bile canaliculi system, which was disrupted by cholestasis-inducing drugs such as troglitazone. Organoids incubated with free fatty acids had gene expression signatures similar to those of liver tissues from patients with NASH. Incubation of organoids with free fatty acid-enriched media resulted in structural changes associated with nonalcoholic fatty liver disease, such as decay of bile canaliculi network and ductular reactions. CONCLUSIONS: We developed a hepatic organoid platform with human cells that can be used to model complex liver diseases, including NASH.

Protective effect of microRNA­381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.

Coronary heart disease (CHD) is the leading cause of human morbidity and mortality worldwide. MicroRNA (miRNA) profiling is an innovative method of identifying biomarkers for many diseases and may be a powerful tool in the diagnosis and treatment of CHD. The present study aimed to analyze the effects of miRNA (miR)­381 on the inflammatory damage of endothelial cells during CHD. A total of 21 patients with CHD and 21 healthy control patients were enrolled in this study. Reverse transcription­quantitative PCR, western blotting and immunofluorescence assays were conducted to examine the expression levels of miR­381, C­X­C chemokine receptor type 4 (CXCR4), Bcl­2, Bax, Cleaved­Caspases­3 and ­9, p38, ERK1/2 and JNK. Cell Counting Kit­8, EdU and flow cytometry experiments were performed to evaluate cell proliferation and apoptosis. An ELISA was adopted to determine the expressions of inflammatory factors (interleukins­8, ­6 and ­1ß, and tumor necrosis factor­α). In addition, a dual­luciferase reporter assay was used to determine the relationship between miR­381 and CXCR4. Decreased miR­381 expression and increased CXCR4 expression in the plasma were observed in the CHD group compared with the normal group, which indicated a negative relationship between miR­381 and CXCR4. Overexpression of miR­381 significantly promoted the proliferation and inhibited the apoptosis of oxidized low­density lipoprotein (OX­LDL)­induced human umbilical vein endothelial cells (HUVECs) through mitogen­activated protein kinase pathway by targeting and inhibiting CXCR4. Furthermore, overexpression of miR­381 reduced the release of inflammatory factors in OX­LDL­induced HUVECs. By contrast, reduced expression of miR­381 exerted the opposite effects, which were subsequently reversed by silencing CXCR4 expression. Results from the present study indicated that miR­381 was a CHD­related factor that may serve as a potential molecular target for CHD treatment.

APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells.

BACKGROUND/AIM: Contrast-induced AKI (CI-AKI) is an important clinical complication of intravascular use of iodinated contrast agents. The aim of the present study was to investigate the renoprotective effect of Apela on contrast-induced acute kidney injury. MATERIALS AND METHODS: Blood samples from patients exposed to iodinated contrast agent were collected to assay for Apela and creatinine levels. The effects of ELA32 (Apela 32) on iodixanol-induced apoptosis, inflammation response, mitochondrial ROS production and DNA damage were examined in NRK-52E renal tubular epithelial cells. RESULTS: Plasma Apela levels were decreased in patients exposed to the contrast agent. Iodixanol-induced apoptosis was reduced in ELA32 treated NRK-52E cells (p<0.05). ELA32 treatment inhibited iodixanol-induced mitochondrial ROS generation (p<0.01). Iodixanol-induced inflammatory cytokines TNFa and IL-6 and inflammatory genes Nrf2 and ICAM-1 were reduced by ELA32 treatment (p<0.01). Reduced Apela expression in iodixanol-treated cells was partially restored by ELA32 treatment (p<0.05). ELA32 treatment suppressed iodixanol-induced up-regulation of DNA damage-associated gene P-ATR and p-CHK1 as well as apoptosis-associated gene C-caspase 3 (p<0.05). CONCLUSION: Administration of iodinated contrast agent reduces Apela expression. ELA32 treatment reduces iodixanol-induced apoptosis, inflammatory response and mitochondrial and DNA damage in renal tubular epithelial cells.

Mitral annular calcification is associated with atrial fibrillation and major cardiac adverse events in atrial fibrillation patients: A systematic review and meta-analysis.

BACKGROUND: The incidence of atrial fibrillation (AF) varies from 5.4% to 47.1% in patients with mitral annulus calcification (MAC). We conducted a systematic review and meta-analysis on the association between MAC and AF, as well as the relation between MAC and major cardiac adverse events (MACEs) in AF patients. METHODS: We conducted comprehensive search for literature on associations between MAC and AF using the following databases: MEDLINE, PubMed, Embase, and the Web of Science. The pooled odds ratio (OR) or relative risk and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between MAC and AF, as well as the rates of MACEs in AF patients with or without MAC. RESULTS: Thirteen studies met our eligibility criteria on associations between MAC and AF, including 6232 patients with MAC and 15,199 patients without MAC. Moreover, 5 studies met our eligibility criteria on the rates of MACEs in AF patients with or without MAC. The pooled analysis demonstrated a statistically significant increased risk of development of incident AF in patients with MAC than those without MAC (random effects OR: 2.34; 95% CI: 1.91, 2.85; P = .000). And the pooled analysis demonstrated a statistically significant increased risk of development of MACEs in AF patients with MAC (random effects OR: 2.34; 95% CI: 1.24, 4.41; P = .009). CONCLUSION: MAC was independently associated with AF and AF patients with MAC were at greater risk for cardiovascular and cerebrovascular events.

Detection of Echinococcus multilocularis in domestic dogs of Shiqu County in the summer herding.

Alveolar echinococcosis (AE) is one of the most serious parasitic zoonosis in Asia. Shiqu County is the most important endemic area of AE in China. Our primary objective is to find out the risk factors for Echinococcus multilocularis infection in domestic dogs in Shiqu County during the summer herding period. A total of 120 fecal samples were collected from 60 ranchers in October 2016. Nested PCR (nPCR) was performed to amplify regions of the mitochondrial12S rRNA gene of E. multilocularis. The results showed that the infection rates of AE in dogs from Qiwu, Yiniu, Changshaganma, Derongma, Mengyi, and Xiazha villages were 5, 5, 10, 20, 10, and 5%, respectively. It should be stressed that the infected dogs will shed eggs through feces and may have a habit of preying on rodents, the intermediate host of the parasite, and become re-infected. This investigation confirmed the presence of E. multilocularis infection in dogs in Shiqu and revealed the risk factors associated with the infection during summer herding.

MiR-26b regulates 5-FU-resistance in human colorectal cancer via down-regulation of Pgp.

Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU in vitro and enhanced the potency of 5-FU in the inhibition of tumor growth in vivo. We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.

Three-Phase Adaptive Radiation Therapy for Patients With Nasopharyngeal Carcinoma Undergoing Intensity-Modulated Radiation Therapy: Dosimetric Analysis.

Patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy may experience significant anatomic changes throughout the entire treatment course, and adaptive radiation therapy may be necessary to maintain optimal dose delivered both to the targets and to the critical structures. The timing of adaptive radiation therapy, however, is largely unknown. This study was to evaluate the dosimetric benefits of a 3-phase adaptive radiation therapy technique for nasopharyngeal carcinoma. Twenty patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy were recruited prospectively. After fractions 5 and 15, each patient had repeat computed tomography scans, and adaptive replans with recontouring the targets and organs at risk on the new computed tomography images were generated and used for subsequent treatment (replan 1 and replan 2). Two hybrid intensity-modulated radiation therapy plans (plan 1 and plan 2) were generated by superimposing the initial plan (plan 0) to each repeated new computed tomography image, reflecting the actual dose delivered to the targets and organs at risk if no changes were made to the original plan. Dosimetric comparisons were made between the adaptive replans (adaptive radiation therapy plans: plan 0 + replan 1 + replan 2) and their corresponding nonadaptive radiation therapy plans (plan 0 + plan 1 + plan 2). Comparing with the nonadaptive radiation therapy plans, the adaptive radiation therapy plans resulted in a significant improvement in conformity index for planning target volumes for primary disease, involved lymph node, high-risk clinical target volume, and low-risk clinical target volume (PTVnx, PTVnd, PTV1, and PTV2, respectively). Median V95 for PTVnx; D95, D99, V100, V95, and V93 for PTVnd; D99 and V100 for PTV1; and D95, D99, V100, V95, and V93 for PTV2 were increased significantly. There were significant dose-volume reductions, including maximum doses to the brainstem and temporal lobes, mean doses to the glottis, V50 for the supraglottis, Dmean and V30 for the left parotid, median dose to the right optic nerve, and V55 for the skin. The 3-phase adaptive intensity-modulated radiation therapy for patients with nasopharyngeal carcinoma results in improvements in target coverage and conformity index and decreased doses to some organs at risk.

Determining appropriate timing of adaptive radiation therapy for nasopharyngeal carcinoma during intensity-modulated radiation therapy.

BACKGROUND: To determine appropriate timing of an adaptive radiation therapy (ART) replan by evaluating anatomic and dosimetric changes of target volumes and organs at risk (OARs) during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS: Nineteen NPC patients were recruited. Each patient had repeat computed tomography (CT) scans after each five fractions and at treatment completion. Automatic re-contouring the targets and OARs by using deformable registration algorithm was conducted through CT-CT fusion. Anatomic changes were assessed by comparing the initial CT and repeated CT. Hybrid plans with re-contouring were generated and the dose-volume histograms (DVH) of the hybrid plan and the original plan were compared. RESULTS: Progressive volume reductions in gross target volume for primary disease (GTVnx), gross target volume for involved lymph nodes (GTVnd), and parotids were observed over time. Comparing with the original plan, each hybrid plan had no significant difference in homogeneity index (HI) for all the targets. Some parameters for planning target volumes for primary disease and high-risk clinical target volume (PTVnx and PTV1, respectively) improved significantly, notably starting from the 10th fraction. These parameters included mean dose (Dmean), dose to 95% of the volume (D95), percentage of the volume receiving 95% of the prescription dose (V95), and conformity index (CI) for PTVnx, and Dmean, D95, and CI for PTV1. The dosimetric parameters for PTVnd remained the same in general except for D95 and V95 which had significant improvement at specific time points; whereas for PTV2, similar trend of dosimetric changes was also observed. Dose to some OARs increased significantly at some time points. CONCLUSIONS: There were significant anatomic and dosimetric changes in the targets and OARs. The target dose coverage in the hybrid plans did not get worse, but overdose occurred in some critical structures. Significant dosimetric changes should be considered as a trigger point at which ART replanning is indicated. D95/V95/CI for PTV2, Dmax for the brain stem, spinal cord, right eyeball and left lens, and Dmean/V30 for the parotids and glottis were taken into account for predicting the need for ART. Two replans at the 5th and 15th fractions were suggested.

Dosimetric study of a respiratory gating technique based on four-dimensional computed tomography in non-small-cell lung cancer.

This study sought to compare the differences in target volumes and dose distributions to the targets and organs at risk (OARs) between a four-dimensional computed tomography (4DCT)-based respiratory-gated intensity-modulated radiation therapy (IMRT) plan (PlanEOE) and a three-dimensional CT (3DCT)-based IMRT plan (Plan3D) in patients with non-small-cell lung cancer (NSCLC). For 17 patients with Stages I-III NSCLC, both 4DCT data and conventional 3DCT data were obtained. The Plan3D and PlanEOE were designed based on 3DCT data and 4DCT data, respectively. The displacements of the gross tumor volume (GTV) centroid were 0.13 ± 0.09 cm, 0.15 ± 0.1 cm, and 0.27 ± 0.27 cm in the right-left, anterior-posterior, and superior-inferior directions, respectively. The volume of the GTVEOE was 3.05 ± 5.17 cm(3) larger than that of the GTV3D. The volume of the PTV3D was 72.82 ± 48.65 cm(3) larger than that of the PTVEOE. There was no significant difference between the PTV3D and PTVEOE for V55.8, V60, V66 and the homogeneity index. The PTV3D had a lower target conformity index than the PTVEOE (P = 0.036). PlanEOE had a significantly lower lung V10, V20, V30, V40 and mean lung dose (MLD) than Plan3D. For the heart, PlanEOE had a significantly lower V30 and mean dose. In conclusion, 4DCT is an appropriate method for assessing the displacement of the GTV centroid in three dimensions. PlanEOE has smaller PTVs and a decreased dose and volume for the normal lung and heart, as compared with Plan3D.