Anlotinib hydrochloride consolidation after concurrent chemoradiotherapy in stage III non-small-cell lung cancer: a truncated, randomized, multicenter, clinical study (ALTER-L029).

Anlotinib is an antiangiogenic drug that shows good efficacy and safety in patients with advanced non-small-cell lung cancer (NSCLC). This study aimed to explore the efficacy and safety of anlotinib for consolidation therapy in patients with stage III locally advanced, unresectable NSCLC after concurrent chemoradiotherapy (cCRT). This was a randomized, parallel-controlled, open-label, multicenter, phase II trial of patients with unresectable/nonoperated NSCLC treated with cCRT. The participants were randomized 2:1 to the anlotinib or control group. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the disease control rate (DCR) and overall survival. This study was terminated early due to poor recruitment. Nine and two participants were randomly assigned to the anlotinib and control groups, respectively. One participant in the control group was excluded due to taking prohibited medications before the first efficacy evaluation. In the anlotinib group, the median age was 63 (range, 37-74) years. Two participants achieved partial response, six stable disease, and one progressive disease as best response. The DCR was 88.9%. The median PFS was 11.5 months, and the 12-month PFS rate was 33.9%. All related adverse events were grade 1 or 2. Two participants had a dose adjustment during the study. The evaluable data suggest that anlotinib alone was effective and tolerable in consolidation therapy after cCRT in patients with stage III unresectable NSCLC. The results need to be confirmed by a large-sample trial. This clinical trial was registered on www.clinicaltrials.gov (NCT03743129). Registration date: 6 September 2018.

Prognostic and predictive impact of abnormal signal volume evolution early after chemoradiotherapy in glioblastoma.

INTRODUCTION: This study was designed to explore the feasibility of semiautomatic measurement of abnormal signal volume (ASV) in glioblastoma (GBM) patients, and the predictive value of ASV evolution for the survival prognosis after chemoradiotherapy (CRT). METHODS: This retrospective trial included 110 consecutive patients with GBM. MRI metrics, including the orthogonal diameter (OD) of the abnormal signal lesions, the pre-radiation enhancement volume (PRRCE), the volume change rate of enhancement (rCE), and fluid attenuated inversion recovery (rFLAIR) before and after CRT were analyzed. Semi-automatic measurements of ASV were done through the Slicer software. RESULTS: In logistic regression analysis, age (HR = 2.185, p = 0.012), PRRCE (HR = 0.373, p < 0.001), post CE volume (HR = 4.261, p = 0.001), rCE1m (HR = 0.519, p = 0.046) were the significant independent predictors of short overall survival (OS) (< 15.43 months). The areas under the receiver operating characteristic curve (AUCs) for predicting short OS with rFLAIR3m and rCE1m were 0.646 and 0.771, respectively. The AUCs of Model 1 (clinical), Model 2 (clinical + conventional MRI), Model 3 (volume parameters), Model 4 (volume parameters + conventional MRI), and Model 5 (clinical + conventional MRI + volume parameters) for predicting short OS were 0.690, 0.723, 0.877, 0.879, 0.898, respectively. CONCLUSION: Semi-automatic measurement of ASV in GBM patients is feasible. The early evolution of ASV after CRT was beneficial in improving the survival evaluation after CRT. The efficacy of rCE1m was better than that of rFLAIR3m in this evaluation.

Pre-anesthesia ultrasound monitoring of subclavian vein diameter changes induced by modified passive leg raising can predict the occurrence of hypotension after general anesthesia: a prospective observational study.

BACKGROUND: Perioperative hypotension increases postoperative complication rates and prolongs postoperative recovery time. Whether Passive Leg Raising test (PLR) and Subclavian Vein Diameter (DSCV) can effectively predict post-anesthesia hypotension remains to be tested. This study aimed to identify specific predictors of General Anesthesia (GA)induced hypotension by measuring DSCV in the supine versus PLR position. METHODS: A total of 110 patients who underwent elective gynecological laparoscopic surgery under general anesthesia, were enrolled in this study. Before anesthesia, DSCV and theCollapsibility Index of DSCV(DSCV-CI) were measured by ultrasound, and the difference in maximal values of DSCV between supine and PLR positions was calculated, expressed as ΔDSCV. Hypotension was defined as Mean Blood Pressure (MBP) below 60mmhg or more than 30% below the baseline. Patients were divided into two groups according to the presence (Group H) or absence (Group N) of postanesthesia hypotension. The area under the receiver operating characteristic curve (ROC) and logistic regression analyses were used to evaluate the predictability of DSCV and other parameters for predicting preincision hypotension. RESULTS: Three patients were excluded due to unclear ultrasound scans, resulting in a total of 107 patients studied. Twenty-seven (25.2%) patients experienced hypotension. Area under the ROC curve of ΔDSCV was 0.75 (P < 0.001) with 95% confidence interval (0.63-0.87), while DSCV and DSCV-CI were less than 0.7. The odds ratio (OR)of ΔDSCV was 1.18 (P < 0.001, 95%CI 1.09-1.27) for predicting the development of hypotension. ΔDSCV is predictive of hypotension following induction of general anesthesia. CONCLUSIONS: ΔDSCV has predictive value for hypotension after general anesthesia. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry on 04/10/2021.

Two-stage nomogram models in mid-gestation for predicting the risk of spontaneous preterm birth in twin pregnancy.

PURPOSE: This study aimed to develop two-stage nomogram models to predict individual risk of preterm birth at < 34 weeks of gestation in twin pregnancies by incorporating clinical characteristics at mid-gestation. METHODS: We used a case-control study design of women with twin pregnancies followed up in a tertiary medical centre from January 2018 to March 2019. Maternal demographic characteristics and transvaginal cervical length data were extracted. The nomogram models were constructed with independent variables determined by multivariate logistic regression analyses. The risk score was calculated based on the nomogram models. RESULTS: In total, 65 twin preterm birth cases (< 34 weeks) and 244 controls met the inclusion criteria. Based on univariate and multivariate logistic regression analyses, we built two-stage nomogram prediction models with satisfactory discrimination and calibration when applied to the validation sets (first-stage [22-24 weeks] prediction model, C-index: 0.805 and 0.870, respectively; second-stage [26-28 weeks] prediction model, C-index: 0.847 and 0.908, respectively). Restricted cubic splines graphically showed the risk of preterm birth among individuals with increased risk scores. Moreover, the decision curve analysis indicated that both prediction models show positive clinical benefit. CONCLUSION: We developed and validated two-stage nomogram models at mid-gestation to predict the individual probability of preterm birth at < 34 weeks in twin pregnancy.

Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA-96.

Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. TP53TG1 is a recently identified lncRNA and several studies have shown that TP53TG1 may play the role of tumor suppressor gene or oncogene in different tumors. Nevertheless, the involvement of TP53TG1 in carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) has not been characterized. In our studies, we identified that TP53TG1 was highly expressed in PDAC and was a novel regulator of PDAC development. Knockdown of TP53TG1 inhibited proliferation, induced apoptosis, and decreased migration and invasion in PDAC cells, whereas enhanced expression of TP53TG1 had the opposite effects. Mechanistically, TP53TG1 could directly bind to microRNA (miR)-96 and effectively function as a sponge for miR-96, thus antagonizing the functions of miR-96 and leading to derepression of its endogenous target KRAS, which is a core oncogene in the initiation and maintenance of PDAC. Taken together, these observations imply that TP53TG1 contributes to the growth and progression of PDAC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-96 and regulate KRAS expression, which highlights the importance of the complicated miRNA-lncRNA network in modulating the progression of PDAC.

Diffuse cavernous hemangioma of the skull misdiagnosed as skull metastasis in breast cancer patient: one case report and literature review.

BACKGROUND: Primary intraosseous cavernous hemangiomas (PICHs) of the skull are extremely rare. To date, diffuse cranial hemangioma of skull has not been reported. In cancer patients, it is often misdiagnosed as metastasis. CASE PRESENTATION: Here, we presented a case of a 50-year-old female patient suffering from slightly headache who received breast cancer modified radical mastectomy in 2004, computed tomography and magnetic resonance imaging findings revealed abnormal lesions of diffuse skull which were misdiagnosed as skull metastasis, and the relevant literatures were also reviewed. CONCLUSIONS: Diffuse cavernous hemangioma of the skull is exceedingly rare, and imaging data are not typical. The condition is often misdiagnosed, and pathological evaluation is necessary and important. In cases where the mass cannot be completely removed by surgery, radiotherapy could be beneficial.

Insulin chains as efficient fusion tags for prokaryotic expression of short peptides.

Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting. All recombinant products were expressed in inclusion bodies. The effective accumulation of products was largely attributed to the insoluble expression induced by fusion with insulin chains, and was confirmed by the fusion expression of transthyretin. Insulin chains thus show promise as efficient fusion tags for mass production of heterologous peptides in prokaryotes.

Complex roles of NRAGE on tumor.

NRAGE, also known as Dlxin-1or MAGE-D1, is a member of type II melanoma-associated antigen (MAGE) and plays an essential role in life activities, including differentiation, apoptosis, and cell cycle. Studies increasingly found that NRAGE is closely related to the tumor events, such as tumor occurrence, invasion, and metastasis. However, complex and contradictory functions of NRAGE in different circumstances are observed, suggesting that NRAGE is unique from other MAGE gene family members. This review summarizes recent findings concerning the structure and biological functions of NRAGE, which may provide a basis for a more comprehensive understanding of and further research on NRAGE.

Identification of novel NRAGE involved in the radioresistance of esophageal cancer cells.

Radiotherapy (RT) is one main method for the treatment of esophageal squamous cell carcinoma (ESCC), and the radioresistance is the predominant cause of patients with local recurrence. The previous results of gene microarray and subsequent verification showed that NRAGE might be involved in radiation resistance of ESCC cells. In this study, we reestablished human esophageal carcinoma radioresistant cell lines TE13R120 and ECA109R60 with gradient dose irradiation as previously reported, respectively. NRAGE expression was high in TE13R120 and ECA109R60 cells and was correlative with ionizing radiation (IR) resistance in clinic. However, the radiosensitivity of TE13R120 cells had a remarkable increase detected by colony formation assays after siRNA against NRAGE (siNRG) transfection into TE13R120 cells. Compared with TE13 cells, an increasing number of TE13R120 cells with NRAGE overexpression in S phase and a lower ratio in G2/M were observed by flow cytometry method (FCM). Intriguingly, the above changes were partially reversed in TE13R120 cells treated with siNRG. More importantly, the ectopic subcellular localization of NRAGE mediated nuclear translocation of ß-catenin which may be one reason of IR resistance of esophageal carcinoma cell. These data indicate that NRAGE extremely may be a pivotal factor involved in Wnt/ß-catenin signal pathway, mediating nuclear translocation of ß-catenin and then facilitating the formation of radioresistance of ESCC.

NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells.

N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.

Pediatric H3K27M­mutant diffuse midline glioma with vertebral metastasis: A case report and literature review.

H3K27M-mutant diffuse midline glioma (DMG) is a type of high-grade glial tumor, which occurs in the midline structure and develops mostly in children. Extraneural metastases (ENM) are exceedingly rare in patients with H3K27M-mutant DMG. A 9-year-old male patient presented with a headache, nausea and vomiting. Following magnetic resonance imaging and immunohistochemical molecular testing examination, the patient was diagnosed with H3K27M-mutant DMG and received chemoradiotherapy plus five cycles of chemotherapy with temozolomide intermittently as an adjuvant therapy. The treatment resulted in a slight reduction of the tumor volume. However, 2 months later, the patient was admitted to hospital with complaints of drooping of the mouth, and waist and back pain. Magnetic resonance imaging and positron-emission tomography-computed tomography revealed an unusual presentation with multiple vertebral metastases and craniospinal leptomeningeal dissemination. Following discussion between the members of a multidisciplinary medical team, the patient underwent one cycle of chemotherapy with cyclophosphamide, vincristine and cisplatin. However, the condition did not improve and the patient died 4 weeks after the diagnosis of ENM. The mechanisms underlying the development of these rare metastases remain unclear. The present case report provides insights into the clinical characteristics and potential metastasis mechanisms of this aggressive disease and may help to elucidate new pathways for the management of ENM.

HMGB2 is a biomarker associated with poor prognosis promoting radioresistance in glioma by targeting base excision repair pathway.

BACKGROUND: High mobility group box 2 (HMGB2) is considered as a biomarker of poor prognosis in various cancers.This study aims to investigate the effect and mechanism of HMGB2 in gliomas. METHODS: With the glioma related on-line and our local hospital databases, the expression differences of HMGB2,Kaplan-Meier survival analysis and COX regression analysis were performed.The correlation analysis between the clinicopathological features and imaging parameters with the HMGB2 expression had been done. Then GSEA and PPI networks were carried out to find out the most significant pathway. The pathway inhibitor was applied to verify HMGB2's participation. CCK8,EDU assays,γ-H2AX immunofluorescence staining and colony formation assay were conducted to observe effects on glioma cells. RESULTS: Available datasets showed that HMGB2 was highly expressed in glioma and patients with high expression of HMGB2 had poorer prognosis and molecular characteristics. Protein level evidence of western blot and immunohistochemistry from our center supported the conclusions above. Analysis on imaging features suggested that HMGB2 expression level had an inverse association with ADCmean but positively with the thickness of enhancing margin. Results from GSEA and PPI network analysis exhibited that HMGB2 was involved in base excision repair (BER) signaling pathway. Experimental evidence demonstrated that the overexpression of HMGB2 promoted the proliferation of glioma cells and enhanced the radio-resistance. CONCLUSIONS: HMGB2 could promote glioma development and enhance the radioresistance of glioma cells, potentially related to the BER pathway, suggesting it may serve as an underlying biomarker for patients with glioma.

A century-long China homogenized daily surface air temperature dataset (CUG-CMA CHDT).

Daily meteorological observation data of the early period (pre-1950) were critically important for investigating the long-term trends and multi-decadal scale variability of extreme climate events. The high-resolution surface air temperature (SAT) data for time period before 1950 are lacking in China. We extended the SAT observations of China back to 1840 through developing a pre-1950 daily SAT dataset. The early-period daily SAT were manually corrected for the input and clerical errors, and then according to the length or coverage of time, the main series for each of the cities was determined. The observation time system of unknown sites was determined by the minimum difference method. After these operations, the data of all sites were unified into the same format. By using the ridge regressions established based on data from modern reference stations, the missing maximum temperature (Tmax) and minimum temperature (Tmin) were interpolated. The early-period data were combined with modern data to form the long-term daily SAT dataset of 1840-2020 in China. RHtest software was used to detect and adjust the inhomogeneities in the station data series. Finally, the century-long homogenized daily SAT dataset including 45 key city stations in China was obtained. Among the stations, there are 20 stations with observation record more than one hundred years. The length of temperature observation series of 17 stations is between 80 and 100 years. The series length of the remaining 7 stations is between 68 and 80 years. Finally, the angular distance weighting (ADW) method was used to interpolate the data into grid products, and the grid size is 2.5 ° × 2.5 °. The dataset was named CUG-CMA CHDT, which is applicable in monitoring, studies and assessments of regional extreme temperature change and variability in China.

Phenyl linker-induced dense PEG conformation improves the efficacy of C-terminally monoPEGylated staphylokinase.

PEGylation can improve the protein efficacy by prolonging serum half-life and reducing proteolytic sensitivity and immunogenicity. However, PEGylation may decrease the bioactivity of a protein by interfering with binding of its substrate or receptors. Here, staphylokinase (SAK), a thrombolysis agent for therapy of myocardial infarction, was mono-PEGylated at the C-terminus of SAK far from its bioactive domain. Phenyl, propyl, and amyl moieties were used as linkers between SAK and polyethylene glycol (PEG), respectively. Flexible propyl and amyl linkers lead to loose conformation. In contrast, rigid and hydrophobic phenyl linker induces dense PEG conformation that can extensively shield most domains adjacent to C-terminus (e.g., the antigen epitopes and proteolytic sites) of SAK and inefficiently shield its bioactive domain. As compared with loose PEG conformation, dense PEG conformation is more efficient to maintain the bioactivity, increase the plasma half-life, and decrease the proteolytic sensitivity and immunogenicity of the PEGylated SAK.

The study of an anoikis-related signature to predict glioma prognosis and immune infiltration.

BACKGROUND: Gliomas are the most common highly aggressive primary malignant brain tumors in adults with different biological behaviors and clinically heterogeneous features. About the extremely poor prognosis of gliomas, the search for potential therapeutic modalities and targets is crucial. METHOD: We extracted the anoikis-related genes (ARG) from GeneCards and obtained differentially expressed genes in normal and glioma tissues from the GSE4290 dataset to obtain intersect differentially expressed ARG in gliomas by differential analysis. KEGG and GO analyses were used to evaluate the potential pathways and molecular processes of these genes. Based on The Cancer Genome Atlas (TCGA) training cohort, we performed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression to construct an ARG prognostic model and validated them in the TCGA testing cohort and the Chinese Glioma Genome Atlas (CGGA) validation cohort. Subsequently, we further explored the differences in clinical characteristics, tumor mutation burden (TMB), and the immune microenvironment in the high- and low-risk groups. Univariate and multifactorial regression analyses and nomogram construction were also performed. Moreover, we evaluated the expression levels of key genes via public databases, qPCR analysis and IHC staining, and further assessed the clinical prognostic value. RESULTS: The regulatory model based on quantitative ARG prognostic models showed that patients in the high-risk group were associated with poorer survival prognosis, poorer clinical characteristics, and higher TMB levels. Moreover, the high-risk group had high levels of immune infiltration and upregulated immune checkpoint gene expression. The ARG prognostic model and the Nomogram showed good predictive performance. Expression and survival analysis of five prognostic ARG signatures (ETV4, HMOX1, MYC, NFE2L2, and UBE2C) showed that these genes have potential prognostic value. CONCLUSION: Our constructed ARG prognostic risk model provides a potential therapeutic target and theoretical basis for predicting the prognosis of glioma patients and guiding individualized immunotherapy.

IDH1R132H mutation increases radiotherapy efficacy and a 4-gene radiotherapy-related signature of WHO grade 4 gliomas.

The prognosis for the WHO grade 4 IDH-mutant astrocytoma is better than IDH-wildtype glioblastoma (GBM) patients. The purpose of this study is to explore the potential mechanism of how IDH1 mutation can increase the efficacy of radiotherapy and to establish a risk-score model to predict the efficacy of radiotherapy in WHO grade 4 gliomas. First, we conducted experimental study on the effect of IDH1R132H mutation on glioma cells in vitro. Radiosensitivity of glioma cells was detected by γ-H2AX after 5 Gy radiation. Cell proliferation, migration and invasion were determined respectively by CCK-8, EDU, monolayer cell migration scratch assay and Transwell assay. Then we analyzed IDH1 gene status and the survival of WHO grade 4 glioma patients received radiotherapy in our center and verified our results by analyzing CGGA and TCGA database. For the risk-score model, we use CGGA data to find genetic differences between WHO grade 4 IDH-mutant astrocytoma and IDH-wildtype GBM patients, and determined a 4-gene radiotherapy-related signature through survival analysis by R software. Evaluation and verification through different glioma validation sets and different statistical methods. For in vitro experiments, we established glioma cells stably overexpressing IDH1 wild-type and IDH1-mutant proteins. γ-H2AX assay showed that IDH1-mutant glioma cells had higher radiosensitivity than wild-type. CCK-8 and EDU assay showed that proliferation capacity of IDH1-mutant glioma cells declined. Transwell assay and monolayer cell migration scratch assay also showed that IDH1-mutant glioma cells reduced migration and invasion capabilities. Among the 83 WHO grade 4 glioma patients who received radiotherapy in our center, WHO grade 4 IDH-mutant astrocytoma patients had longer OS and PFS versus IDH-wildtype GBM (P = 0.0336, P = 0.0324, respectively). TCGA and CGGA database analysis had the similar results. Through complex analysis of CGGA and TCGA databases, we established a risk-model that can predict the efficacy of radiotherapy for WHO grade 4 glioma patients. The 4-gene radiotherapy-related signature including ADD3, GRHPR, RHBDL1 and SLC9A9. Patients in the high-risk group had worse OS compared to low-risk group (P = 0.0001). High- and low-risk groups of patients receiving radiotherapy have significant survival differences, while patients who did not receive radiotherapy have no survival difference both in CGGA and TCGA databases. WHO grade 4 IDH-mutant astrocytoma is more radiosensitive than IDH-wildtype GBM patients. Our 4-gene radiotherapy-related signature can predict the radiation efficacy of WHO grade 4 glioma patients, and it may provide some reference for clinical treatment options.

Prenatal diagnosis and postnatal verification in fetuses with total anomalous pulmonary venous connection.

Objective: To systematically verify the accuracy of a four-step prenatal ultrasonography in diagnosing fetal total anomalous pulmonary venous connection (TAPVC). Methods: A total of 62 TAPVC fetuses received prenatal ultrasonography and were confirmed by postnatal echocardiography, surgery, or postabortion autopsy. The suspected TAPVC fetuses were further screened by a four-step prenatal ultrasonography for TAPVC classification, pulmonary venous obstruction, and the associated malformations, and followed postpartum. The sonographic features, clinical data, and prognosis of the TAPVC fetuses were retrospectively analyzed. Results: Of the 62 TAPVC fetuses, supracardiac TAPVC was found in 20 cases, intracardiac TAPVC in 12, infracardiac TAPVC in 21, and mixed TAPVC in 9. A total of 30 cases with right atrium isomerism were correctly diagnosed. Of the 11 cases with other intracardiac and extracardiac malformations, 1 case was missed to be diagnosed. Of the 21 isolated TAPVC cases, 6 were missed prenatally and 1 case was prenatally diagnosed as intracardiac and postnatally proved to be mixed (intracardiac type + supracardiac type) by echocardiography. Of the 13 TAPVC live births, 4 infants died in the neonatal period without operation. Of the nine infants undergoing the operation, five recuperated and survived; one survived but had complications with superior vena cava obstruction and collateral circulation formation, and three died postoperatively. Conclusion: The four-step prenatal ultrasound procedure can comprehensively and systematically evaluate fetal TAPVC, detailing the classification, potential obstruction, and associated malformations. It provides substantial support for subsequent prenatal counseling and neonatal assessment. The retrospective analysis also reveals that isolated TAPVC is more prone to be missed in diagnosis.

Radiation Oncology Research in Asia: Current Status and a Peep Into the Future From the Federation of Asian Organizations for Radiation Oncology.

PURPOSE: This survey was conducted to assess the current research practices among the 14 members of the Federation of Asian Organizations for Radiation Oncology (FARO) committee, to inform measures for research capacity building in these nations. MATERIALS AND METHODS: A 19-item electronic survey was sent to two research committee members from the 14 representative national radiation oncology organizations (N = 28) that are a part of FARO. RESULTS: Thirteen of the 14 member organizations (93%) and 20 of 28 members (71.5%) responded to the questionnaire. Only 50% of the members stated that an active research environment existed in their country. Retrospective audits (80%) and observational studies (75%) were the most common type of research conducted in these centers. Lack of time (80%), lack of funding (75%), and limited training in research methodology (40%) were cited as the most common hindrances in conducting research. To promote research initiatives in the collaborative setting, 95% of the members agreed to the creation of site-specific groups, with head and neck (45%) and gynecological cancers (25%) being the most preferred disease sites. Projects focused on advanced external beam radiotherapy implementation (40%), and cost-effectiveness studies (35%) were cited as some of the potential areas for future collaboration. On the basis of the survey results, after result discussion and the FARO officers meeting, an action plan for the research committee has been created. CONCLUSION: The results from the survey and the initial policy structure may allow facilitation of radiation oncology research in the collaborative setting. Centralization of research activities, funding support, and research-directed training are underway to help foster a successful research environment in the FARO region.

Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial.

Importance: High-grade gliomas (HGGs) constitute the most common and aggressive primary brain tumor, with 5-year survival rates of 30.9% for grade 3 gliomas and 6.6% for grade 4 gliomas. The add-on efficacy of interferon alfa is unclear for the treatment of HGG. Objectives: To compare the therapeutic efficacy and toxic effects of the combination of temozolomide and interferon alfa and temozolomide alone in patients with newly diagnosed HGG. Design, Setting, and Participants: This multicenter, randomized, phase 3 clinical trial enrolled 199 patients with newly diagnosed HGG from May 1, 2012, to March 30, 2016, at 15 Chinese medical centers. Follow-up was completed July 31, 2021, and data were analyzed from September 13 to November 24, 2021. Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed HGG and had received no prior chemotherapy, radiotherapy, or immunotherapy for their HGG. Interventions: All patients received standard radiotherapy concurrent with temozolomide. After a 4-week break, patients in the temozolomide with interferon alfa group received standard temozolomide combined with interferon alfa every 28 days. Patients in the temozolomide group received standard temozolomide. Main Outcomes and Measures: The primary end point was 2-year overall survival (OS). Secondary end points were 2-year progression-free survival (PFS) and treatment tolerability. Results: A total of 199 patients with HGG were enrolled, with a median follow-up time of 66.0 (95% CI, 59.1-72.9) months. Seventy-nine patients (39.7%) were women and 120 (60.3%) were men, with ages ranging from 18 to 75 years and a median age of 46.9 (95% CI, 45.3-48.7) years. The median OS of patients in the temozolomide plus interferon alfa group (26.7 [95% CI, 21.6-31.7] months) was significantly longer than that in the standard group (18.8 [95% CI, 16.9-20.7] months; hazard ratio [HR], 0.64 [95% CI, 0.47-0.88]; P = .005). Temozolomide plus interferon alfa also significantly improved median OS in patients with O6-methylguanine-DNA methyltransferase (MGMT) unmethylation (24.7 [95% CI, 20.5-28.8] months) compared with temozolomide (17.4 [95% CI, 14.1-20.7] months; HR, 0.57 [95% CI, 0.37-0.87]; P = .008). Seizure and influenzalike symptoms were more common in the temozolomide plus interferon alfa group, with 2 of 100 (2.0%) and 5 of 100 (5.0%) patients with grades 1 and 2 toxic effects, respectively (P = .02). Finally, results suggested that methylation level at the IFNAR1/2 promoter was a marker of sensitivity to temozolomide plus interferon alfa. Conclusions and Relevance: Compared with the standard regimen, temozolomide plus interferon alfa treatment could prolong the survival time of patients with HGG, especially the MGMT promoter unmethylation variant, and the toxic effects remained tolerable. Trial Registration: ClinicalTrials.gov Identifier: NCT01765088.

The current management and biomarkers of immunotherapy in advanced gastric cancer.

BACKGROUND: Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS: WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS: Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION: ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.