Pb nanospheres encapsulated in metal-organic frameworks-derived porous carbon as anode for high-performance sodium-ion batteries.

Alloying-type anode materials are considered promising candidates for sodium-ion batteries (SIBs) due to their high theoretical capacities. However, their application is limited by the severe capacity decay stemming from dramatic volume changes during Na+ insertion/extraction processes. Here, Pb nanospheres encapsulated in a carbon skeleton (Pb@C) were successfully synthesized via a facile metal-organic frameworks (MOFs)-derived method and used as anodes for SIBs. The nanosized Pb particles are uniformly incorporated into the porous carbon framework, effectively mitigating volume changes and enhancing Na+ ion transport during discharging/charging. Benefiting from this unique architecture, a reversible capacity of 334.2 mAh g-1 at 2 A g-1 is achieved after 6000 cycles corresponding to an impressive 88.2 % capacity retention and a minimal capacity loss of 0.00748 % per cycle. Furthermore, a high-performance full sodium-ion battery of Pb@C//NVPF was constructed, demonstrating a high energy density of 291 Wh kg-1 and power density of 175 W kg-1. This facile MOFs-derived method offers insights into the design of high-capacity alloy-type anode materials using Pb sources, opening up new possibilities for innovative approaches to Pb recycling and pollution prevention.

Effectiveness of CT radiomic features combined with clinical factors in predicting prognosis in patients with limited-stage small cell lung cancer.

BACKGROUND: The prognosis of SCLC is poor and difficult to predict. The aim of this study was to explore whether a model based on radiomics and clinical features could predict the prognosis of patients with limited-stage small cell lung cancer (LS-SCLC). METHODS: Simulated positioning CT images and clinical features were retrospectively collected from 200 patients with histological diagnosis of LS-SCLC admitted between 2013 and 2021, which were randomly divided into the training (n = 140) and testing (n = 60) groups. Radiomics features were extracted from simulated positioning CT images, and the t-test and the least absolute shrinkage and selection operator (LASSO) were used to screen radiomics features. We then constructed radiomic score (RadScore) based on the filtered radiomics features. Clinical factors were analyzed using the Kaplan-Meier method. The Cox proportional hazards model was used for further analyses of possible prognostic features and clinical factors to build three models including a radiomic model, a clinical model, and a combined model including clinical factors and RadScore. When a model has prognostic predictive value (AUC > 0.7) in both train and test groups, a nomogram will be created. The performance of three models was evaluated using area under the receiver operating characteristic curve (AUC) and Kaplan-Meier analysis. RESULTS: A total of 1037 features were extracted from simulated positioning CT images which were contrast enhanced CT of the chest. The combined model showed the best prediction, with very poor AUC for the radiomic model and the clinical model. The combined model of OS included 4 clinical features and RadScore, with AUCs of 0.71 and 0.70 in the training and test groups. The combined model of PFS included 4 clinical features and RadScore, with AUCs of 0.72 and 0.71 in the training and test groups. T stages, ProGRP and smoke status were the independent variables for OS in the combined model, whereas T stages, ProGRP and prophylactic cranial irradiation (PCI) were the independent factors for PFS. There was a statistically significant difference between the low- and high-risk groups in the combined model of OS (training group, p < 0.0001; testing group, p = 0.0269) and PFS (training group, p < 0.0001; testing group, p < 0.0001). CONCLUSION: Combined models involved RadScore and clinical factors can predict prognosis in LS-SCLC and show better performance than individual radiomics and clinical models.

Copper and conjugated carbonyls of metal-organic polymers as dual redox centers for Na storage.

Metal-organic polymers (MOPs) are fascinating electrode materials for high-performance sodium-ion batteries due to their multiple redox centers and low cost. Herein, a flower-like π-d conjugated MOP (Cu-TABQ) was synthesized using tetramino-benzoquinone (TABQ) as an organic ligand and Cu2+ as a transition metal node under the slow release of Cu2+ from [Cu(NH3)4]2+ and subsequent dehydrogenation. It possesses dual redox centers of Cu2+/Cu+ and C[double bond, length as m-dash]O/C-O to render a three-electron transfer reaction for each coordination unit with a high reversible capacity of 322.9 mA h g-1 at 50 mA g-1 in the voltage range of 1.0 to 3.0 V. The flower-like structure enhances fast Na+ diffusion and highly reversible organic/inorganic redox centers. This results in excellent cycling performance with almost no degradation within 700 cycles and great rate performance with 198.8 mA h g-1 at 4000 mA g-1. The investigation of the Na-storage mechanism and attractive performance will shed light on the insightful design of MOP cathode materials for further batteries.

Effect of AQP4 and its palmitoylation on the permeability of exogenous reactive oxygen species: Insights from computational study.

Aquaporin 4 (AQP4) facilitates the transport of reactive oxygen species (ROS). Both cancer cells and the ionizing radiation microenvironment can induce posttranslational modifications (PTMs) in AQP4, which may affect its permeability to ROS. Because this ROS diffusion process is rapid, microscopic, and instantaneous within and outside cells, conventional experimental methods are inadequate for elucidating the molecular mechanisms involved. In this study, computational methods were employed to investigate the permeability of exogenous ROS mediated by radiation in AQP4 at a molecular scale. We constructed a simulation system incorporating AQP4 and AQP4-Cysp13 in a complex lipid environment with ROS. Long-timescale molecular dynamics simulations were conducted to assess the structural stability of both AQP4 and AQP4-Cysp13. Free energy calculations were utilized to determine the ROS transport capability of the two AQP4 proteins. Computational electrophysiology and channel structural analysis quantitatively evaluated changes in ROS transport capacity under various radiation-induced transmembrane voltage microenvironments. Our findings demonstrate the distinct transport capabilities of AQP4 channels for water molecules and various types of ROS and reveal a decrease in transport efficiency when AQP4 undergoes palmitoylation modification. In addition, we have simulated the radiation-induced alteration of cell membrane voltage, which significantly affected the ROS transport capacity. We propose that this research will enhance the understanding of the molecular mechanisms governing the transport of exogenous ROS by AQP4 and elucidate the influence of palmitoylation on ROS transport. This study will also help clarify how different structural features of AQP4 affect the transport of exogenous ROS mediated by radiotherapy, thereby providing a theoretical molecular basis for the development of new treatment strategies that combine with radiotherapy.

A V2O5 cathode for aqueous rechargeable Pb-ion batteries.

Aqueous rechargeable metal batteries (AMBs) have attracted great attention and have been regarded as a next-generation promising energy storage system. However, the high-activity metal anodes usually face side reactions, passivation, and hydrogen evolution reactions, which impede the development of high-performance AMBs. Here, we designed and assembled a Pb metal battery based on a highly reversible Pb metal anode and layered V2O5 cathode, which showed good electrochemical performance. This new-type battery will encourage more investigations for high-performance AMBs and open up an innovation pathway for traditional lead-acid batteries.

Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer.

BACKGROUND: The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. METHODS: The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39-0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31-0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1-2. CONCLUSIONS: Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.

Simultaneous integrated dose reduction intensity-modulated radiotherapy effectively reduces cardiac toxicity in limited-stage small cell lung cancer.

OBJECTIVE: To assess the clinical outcomes and toxicities of once daily (QD) simultaneous dose reduction intensity-modulated radiotherapy (SDR-IMRT-QD; SDR-QD) versus conventional QD IMRT (C-QD) and twice daily (BID) IMRT in patients with limited-stage small cell lung cancer (LS-SCLC). METHODS: After propensity score matching (PSM), a retrospective analysis involving 300 patients with LS-SCLC treated using SDR-QD, C-QD, or BID was performed from January 1, 2014 to December 31, 2019. The prescribed irradiation dose in the SDR-QD cohort was 60 Gy/PGTV and 54 Gy/PTV QD. The radiation dose was 60 Gy for both PGTV and PTV QD in the C-QD cohort. The radiation dose was 45 Gy for both PGTV and PTV in the BID cohort. Toxicities, short-term effects, and survival outcomes were recorded. A meta-analysis on the protective effects of pharmaceuticals for cardiac toxicities induced by anti-tumor therapy was performed. RESULTS: The median overall survival time (MST) in the 3 cohorts were 32.7 months (SDR-QD), 26.3 months (C-QD), and 33.6 months (BID); the differences between groups were statistically significant. Lower toxicities and doses to organs-at-risk (OARs) occurred in the SDR-QD and BID cohorts. Further, the cardiac dose dosimetric parameter Vheart40 was negatively associated with survival (r = -0.35, P = 0.007). A Vheart40 value of 16.5% was recommended as a cut-off point, which yielded 54.7% sensitivity and 85.7% specificity for predicting negative survival outcomes. The meta-analysis indicated that pharmaceuticals significantly reduced the cardiac toxicities induced by chemotherapy, but not radiotherapy. CONCLUSIONS: SDR-QD was shown to have similar toxicities and survival compared with BID, but fewer toxicities and better survival than C-QD. In addition, cardiac dose exposure was negatively associated with survival. Thus, 16.5% of the cardiac dosimetric parameter Vheart40 is recommended as the cut-off point, and a Vheart40 > 16.5% predicts poor survival.

Effects of membrane lipids on phospholamban pentameric channel structure and ion transportation mechanisms.

Protein-lipid interactions are an essential element of the function of many membrane ion-channel proteins. These potential interactions should be considered alongside the diversity and complexity of membrane lipid composition. Phospholamban (PLN) is an inhibitor of sarcoplasmic reticulum Ca2+ ATPase (SERCA). PLN is a 52-residue transmembrane protein encoded by lncRNA, and PLN monomers form stable pentamers of biological function in a lipid bilayer membrane. Some earlier studies suggest that it can form a cationic selective channel, while others suggest that it can only store ions. Here, we report the distribution of different lipids in the membrane and the structural dynamics and conductance properties of PLN pentamers after coarse-grained (CG) and all-atom (AA) molecular dynamics simulations of different systems. The results show that cholesterol is highly enriched around the protein and stabilizes the structure of the PLN pentamer. The absence of cholesterol increases the flexibility of the protein backbone. The conductance properties of monovalent ions and water suggest that they cannot spontaneously permeate through the PLN pentamer channel pore. However, the energy barrier to overcome is much lower in the absence of cholesterol, underlining the need to fully consider multiple lipid species when investigating small transmembrane protein oligomer ion-channel structure and conductance.

Practice Patterns of Treatment Strategy of Limited-Stage Small-Cell Lung Cancer: Survey of Chinese Oncologists.

Background: Thoracic radiotherapy (TRT) with concurrent chemotherapy is the standard treatment of limited-stage small-cell lung cancer (LS-SCLC). However, there is still a controversy surrounding the treatment strategy especially optimal dosing and fractionation schedule. Current practice patterns among Chinese oncologists are unknown. Materials and Methods: We surveyed 212 Chinese oncologists using a questionnaire including 50 questions designed by experienced oncologists. Questions covered demographic data, treatment recommendations, and self-assessed knowledge of guidelines or key clinical trials for SCLC. The chi-square test and Fisher's exact test were utilized to describe the result of the study. Results: The response rate was 97% (207/212). Of all the respondents, 69% preferred TRT QD, 29% preferred BID, and 2% chose HFRT. For those who prefer TRT QD, 72% preferred a total dose of 60 Gy, followed by 15% opting for 66 Gy, 12% for <60 Gy, and 1% for 70 Gy. Of those who prefer BID, 79% preferred a total dose of 45 Gy, with 4% choosing 30 Gy, 8% choosing 50 Gy, 7% choosing 54 Gy, and 2% choosing >54 Gy. Regarding PCI, 82% of participants believed that PCI should be performed when treatment is completed and 13% believed that PCI should begin immediately after concurrent chemoradiotherapy. As for other therapies, 26% of participants choose concurrent anti-angiogenic therapy during SCLC treatment, and 49% recommended small-molecule TKI as the main anti-angiogenic therapy. Conclusion: Substantial variation exists in how Chinese oncologists approach TRT dosing and fractionation for LS-SCLC. Almost 70% of respondents reported administering TRT QD more often in daily work. The most common doses were 60 Gy QD and 45 Gy BID.

Prognostic Implications of Molecular Subtypes in Primary Small Cell Lung Cancer and Their Correlation With Cancer Immunity.

Introduction: Small cell lung cancer (SCLC) has recently been characterized as heterogeneous tumors due to consensus nomenclature for distinct molecular subtypes on the basis of differential expression of four transcription markers (ASCL1, NEUROD1, POU2F3, and YAP1). It is necessary to validate molecular subtype classification in primary SCLC tumors by immunohistochemical (IHC) staining and investigate its relevance to survival outcomes. Methods: Using a large number of surgically resected primary SCLC tumors, we assessed the mRNA and protein levels of the four subtype markers (ASCL1, NEUROD1, POU2F3 and YAP1) in two independent cohorts, respectively. Next, molecular subtypes defined by the four subtype markers was conducted to identify the association with clinicopathologic characteristics, survival outcomes, the expression of classic neuroendocrine markers, and molecules related to tumor immune microenvironment. Results: Samples were categorized into four subtypes based on the relative expression levels of the four subtype markers, yielding to ASCL1, NEUROD1, POU2F3 and YAP1 subtypes, respectively. The combined neuroendocrine differentiation features were more prevalent in either ASCL1 or NEUROD1 subtypes. Kaplan-Meier analyses found that patients with tumors of the YAP1 subtype and ASCL1 subtype obtained the best and worst prognosis on both mRNA and IHC levels, respectively. Based on multivariate Cox proportional-hazards regression model, molecular subtype classification determined by IHC was identified as an independent indicator for survival outcomes in primary SCLC tumors. Correlation analyses indicated that the four subtype markers in SCLC cancer cells were interacted with its tumor immune microenvironment. Specifically, tumors positive for YAP1 was associated with fewer CTLA4+ T cell infiltration, while more immune-inhibitory receptors (FoxP3,PD1, and CTLA4) and fewer immune-promoting receptor (CD8) were found in tumors positive for ASCL1. Conclusions: We validated the new molecular subtype classification and clinical relevance on both mRNA and protein levels from primary SCLC tumors. The molecular subtypes determined by IHC could be a pre-selected effective biomarker significantly influenced on prognosis in patients with SCLC, which warrants further studies to provide better preventative and therapeutic options for distinct molecular subtypes.

THE INFLUENCE OF LOW-DOSE OCCUPATIONAL RADIATION EXPOSURE ON PERIPHERAL BLOOD CELLS IN A COHORT OF CHINESE MEDICAL RADIATION WORKERS.

OBJECTIVES: The study aims to assess the change of peripheral blood cell numbers following protracted low-dose radiation exposure among medical radiation workers. METHODS: A cohort of 375 Chinese medical workers were followed for 5 years (2015-19) and recorded the changes in blood cells and cumulative doses. T-test, least significant difference-T test, variance analysis and correlation analysis were utilized in this study. RESULTS: Compared with the control group, the white blood cells, hemoglobin counts and the ratio of eosinophils in the study group showed a downward trend. The differences in blood cells between groups were mainly found in the number of red blood cells. In a short cumulative time, such as 1 or 3 years, a correlation between the cumulative dose and the quantity of blood cells was detected, but not at 5 years. CONCLUSIONS: There is no significant difference in the blood cell counts between different types of work, and the long-term cumulative dose has not been statistically correlated with the number of blood cells. So that the number of peripheral blood cells can no longer be used as a good indicator of radiation damage.

Probing the formation, structure and free energy relationships of M protein dimers of SARS-CoV-2.

The M protein of the novel coronavirus 2019 (SARS-CoV-2) is the major structural component of the viral envelope and is also the minimum requirement for virus particle budding. M proteins generally exist as dimers. In virus assembly, they are the main driving force for envelope formation through lateral interactions and interactions with other viral structural proteins that play a central role. We built 100 candidate models and finally analyzed the six most convincing structural features of the SARS-CoV-2 M protein dimer based on long-timescale molecular dynamics (MD) simulations, multiple free energy analyses (potential mean force (PMF) and molecular mechanics Poisson-Boltzmann surface area (MMPBSA)) and principal component analysis (PCA) to obtain the most reasonable structure. The dimer stability was found to depend on the Leu-Ile zipper motif and aromatic amino acids in the transmembrane domain (TMD). Furthermore, the C-terminal domain (CTD) effects were relatively small. These results highlight a model in which there is sufficient binding affinity between the TMDs of M proteins to form dimers through the residues at the interface of the three transmembrane helices (TMHs). This study aims to help find more effective inhibitors of SARS-CoV-2 M dimers and to develop vaccines based on structural information.

The Addition of Peripheral Blood Inflammatory Indexes to Nomogram Improves the Predictive Accuracy of Survival in Limited-Stage Small Cell Lung Cancer Patients.

BACKGROUND: Accumulated evidence for systemic inflammation response in several solid tumors prompts a possibility of prediction of patients' prognosis in a more accessible and valuable manner. However, the prognostic value of peripheral blood inflammatory markers in limited-stage small cell lung cancer (LS-SCLC) remains unclear. Therefore, we investigated the prognostic values of pretreatment inflammatory indexes in LS-SCLC patients. METHODS: We retrospectively identified 334 patients with LS-SCLC and collected their pretreatment serum levels of neutrophil, platelet, lymphocyte, leukocyte, hemoglobin, and albumin, then neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII) were calculated. Patients were dichotomized as low-Risk or high-Risk group based on their corresponding cutoff values. Univariate and multivariate analyses were conducted with a Cox proportional hazards model. The least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was performed to construct the inflammation-related prognostic scoring system named Risk for OS. Nomograms were established to provide prognostic information, allowing for more individualized prediction of survival. RESULTS: Higher pretreatment platelet, lymphocyte, and albumin were indicators of favorable overall survival (OS), whereas higher NLR and SII were accompanied by inferior OS. The prognosis of patients with high Risk was significantly worse than that with low Risk in both the training group and the validation group (both p < 0.001). Comparable area under the curve (AUC) values between the training group and the validation group were observed, yielding 1-, 3-, and 5-year OS rates of 67.3% vs. 69.2%, 66.8% vs. 69.5%, and 66.7% vs. 71.4%, respectively. Multivariate analyses revealed that Risk [hazard ratio (HR) = 0.551, p < 0.001] was an independent negative prognostic indicator for OS, which was further verified in the validation set. The addition of Risk to nomogram (C-index = 0.643) harbored improved predictive accuracy for OS when compared with that of clinical factors alone (C-index = 0.606); the AUC values of 1-, 3-, and 5-year OS rates were 71.7% vs. 66.4%, 73.5% vs. 66.6%, and 71.9% vs. 65.6%, respectively. CONCLUSIONS: Pretreatment peripheral blood inflammatory indexes may be a noninvasive serum biomarker for poor prognosis in LS-SCLC. The addition of Risk to the nomogram model could serve as a more powerful, economical, and practical method to predict survival for patients with LS-SCLC.

Estimating survival and clinical outcome in advanced non-small cell lung cancer with bone-only metastasis using molecular markers.

OBJECTIVES: This retrospective study investigated prognostic factors in advanced non-small cell lung cancer (NSCLC) with bone-only metastasis, and developed a graded prognostic assessment (GPA) model to estimate patient survival. METHODS: The primary endpoint was overall survival. We investigated the patients with advanced NSCLC with bone-only metastasis at the initial diagnosis and diagnosed between 2013 and 2019 in our hospital. A log-rank test and Cox proportional hazards model were used to examine factors. A GPA model was developed in the training set based on the factors that were determined significant according to their hazard ratios and verified by the validation set. RESULTS: We finally included 220 patients for analysis. These patients were divided into two groups, 147 cases for the training cohort and 73 for the validation cohort. The following were significant independent prognostic factors, and were included in the GPA model: smoking; EGFR (epidermal growth factor receptor) sensitive/ALK (anaplastic lymphoma kinase) mutations; loss of weight; hypoalbuminemia; and primary site treated by surgery or radiotherapy. GPA score of nil was assigned to smoking, without sensitive mutations, loss of weight, hypoalbuminemia, and without local treatment of primary site; the corresponding superior alternatives were scored 1.5, 2.0, 1.5, 1.5, and 1.5, respectively. The median survival times of patients with GPA scores of nil to 3.0, 3.5 to 6.0, and 6.5 to 8.0 were 14.2, 29.5, and 56.6 months in the training set (P < 0.001) and 15.2, 31.2, and 54.0 months in the validation set (P < 0.001). CONCLUSION: The survival time of patients with NSCLC with bone-only metastasis was dramatically influenced by the presence of the determined prognostic factors. The GPA model developed in this study may be a useful clinical tool to estimate the life expectancy of these patients, and guide treatment.

TGFß1 in Cancer-Associated Fibroblasts Is Associated With Progression and Radiosensitivity in Small-Cell Lung Cancer.

OBJECTIVE: Small-cell lung cancer (SCLC) is aggressive, with early metastasis. Cytokines secreted by cancer-associated fibroblasts (CAFs) within various tumors influences these features, but the function in particular of TGFß1 (transforming growth factor beta 1) is controversial and unknown in SCLC. This study explored the influence of TGFß1 in CAFs on the development, immune microenvironment, and radiotherapy sensitivity of SCLC. METHODS: SCLC specimens were collected from 90 patients who had received no treatment before surgery. Tumor and tumor stroma were subjected to multiplex immunohistochemistry to quantitate TGFß1 and other immune factors in CAFs. Cell proliferation and flow cytometry apoptosis assays were used to investigate associations between TGFß1 and proliferation and radiotherapy sensitivity. The immune factors in tumors were detected by immunohistochemistry in vitro and in vivo (mice). RESULTS: TGFß1 levels on CAFs lower or higher than the median were found, respectively, in 52.2 and 47.8% of patients; overall survival of patients with TGFß1-high levels (53.9 mo) was significantly longer than that of the TGFß1-low group (26.9 mo; P = 0.037). The univariate and multivariate analyses indicated that a TGFß1-high level was an independent predictor of increased survival time. TGFß1-high levels in CAFs were associated with inhibition of growth, proliferation, antitumor immunity, and enhanced radiotherapeutic sensitivity and tumor immunity of tumor. TGFß1-low levels promoted tumor cell growth and radiotherapy sensitivity in vivo and in vitro. CONCLUSION: High levels of TGFß1 in CAFs were associated with longer overall survival in patients with SCLC and enhanced radiotherapy sensitivity.

Is a higher estimated dose of radiation to immune cells predictive of survival in patients with locally advanced non-small cell lung cancer treated with thoracic radiotherapy?

BACKGROUND AND PURPOSE: In previous studies, the estimated dose of radiation to immune cells (EDRIC) showed a correlation with overall survival (OS) of patients with locally advanced non-small cell lung cancer (LA-NSCLC) who received thoracic radiotherapy. However, several factors such as gross tumor volume (GTV) and lymph node (N) stage may impact EDRIC. The purpose of this study was to identify the factors influencing EDRIC and to further assess the prognostic relevance of EDRIC. MATERIALS AND METHODS: We retrospectively analyzed 201 patients with LA-NSCLC who received radiotherapy between 2012 and 2017. EDRIC was calculated based on the model developed by Jin et al. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the correlation of potential factors with OS, local progression-free survival (LPFS), and distant metastasis-free survival (DMFS). Spearman's rank correlation was used to assess the correlation between variables. RESULTS: Both GTV and N stage showed a positive correlation with EDRIC (r = 0.347, P < 0.001 and r = 0.249, P < 0.001, respectively). EDRIC was independently associated with DMFS (HR 1.185, P < 0.001). GTV was associated with OS (HR 1.006, P < 0.001), LPFS (HR 1.003, P = 0.017), and DMFS (HR 1.003, P = 0.032). While using GTV as a stratification factor in Kaplan-Meier analysis, EDRIC showed a trend of negative correlation with OS in GTV ≤ 66.6 cm3 group (P = 0.061). CONCLUSION: EDRIC was an independent prognostic factor for metastasis and it was affected by GTV and N stage. However, the effect of EDRIC on OS was influenced by GTV.

One Cycle of Concurrent Chemotherapy vs. Two Cycles of Concurrent Chemotherapy With Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer.

BACKGROUND: The optimal number of concurrent chemotherapy cycles during thoracic radiotherapy (RT) in patients with limited stage-small cell lung cancer (LS-SCLC) is not well defined. The purpose of this study was to evaluate the impact of the number of concurrent chemotherapy cycles on prognosis of LS-SCLC. MATERIAL AND METHODS: Patients with LS-SCLC treated with concurrent chemo-radiotherapy from May 2008 to December 2020 in our hospital were retrospectively analyzed. The prescribed radiation dose was 60Gy administrated with conventional RT in 30 fractions within 6 weeks. The prognostic role of cycle number of chemotherapy administrated concurrently with RT were analyzed. All patients were followed up at one month after the treatment, then once every three months until two years after the treatment, and every six months thereafter. Propensity score matching (PSM) was performed to reduce confounding factors. The primary endpoint was overall survival (OS). Survival analysis was performed with Kaplan-Meier and multivariate analysis was performed with Cox regression model. RESULTS: Among the 370 patients who received radical radiotherapy, 206 patients received concurrent chemo-radiotherapy and were included for the analysis. Multivariate analysis showed that stage and PCI were independent prognostic factors for OS. The median OS in patients who received one cycle and two cycles of chemotherapy concurrently with RT were 32.9 months and 31.6 months, respectively (P = 0.241). And the median PFS were 20.6 months and 18.4 months, respectively (P = 0.764). After PSM, no statistical differences in OS and PFS were observed between patients who received one cycle and those who received two cycles of concurrent chemotherapy. CONCLUSION: Two cycles of concurrent chemotherapy during RT were not necessarily superior compared to one cycle in LS-SCLC. The optimal cycle number of concurrent chemotherapy during RT needs to be further studied.

Safety of apatinib plus S-1 for advanced solid tumor as palliative treatment.

The aim of the present study was to explore the safety of apatinib plus S-1 in treating advanced solid tumors after failure of two or more lines of chemotherapy. A total of 33 patients with advanced cancer treated between April 2016 to March 2019 were retrospectively analyzed. Of these, 13 patients had non-small cell lung cancer (NSCLC), 13 patients had SCLC, 4 patients had esophageal cancer and 3 had cervical cancer. All patients were treated with apatinib 250 mg once daily combined with S-1 60 mg/m2 twice daily for 14 days, repeated every 3 weeks. Adverse reactions were observed until aggravation of adverse reactions beyond the tolerable range or disease progression, and the survival rate and clinical benefits were calculated. The results suggested that the incidence rate of adverse effects (grade 3-4) was 45.5% (15/33). The top three severe adverse effects were hypertension (15.2%), thrombocytopenia (12.1%) and proteinuria (9.1%). A total of 2 patients with lung squamous-cell carcinomas died of severe pulmonary hemorrhage. Other adverse reactions were tolerated in the cohort. A total of 10 patients achieved partial response and the objective response rate was 30.3%. Furthermore, 13 patients achieved stable disease and 10 patients had progressive disease, and accordingly, the disease control rate was 72.7%. In conclusion, apatinib plus S-1 for advanced solid tumor patients as palliative treatment have a certain efficacy and was relatively safe but should be used with caution in patients with squamous-cell lung carcinoma and the efficacy and safety requires further assessment.

Baseline nutritional status could be a predictor for radiation esophagitis in esophageal cancer patients undergoing radiotherapy.

BACKGROUND: To investigate the relationship between baseline nutrition status and radiation esophagitis in patients with esophageal cancer treated by radiation therapy. METHODS: A retrospective study was performed on 100 patients with esophageal cancer who was treated with definitive chemoradiotherapy, preoperative chemoradiation and definitive radiotherapy at the Tianjin Medical University Cancer Institute and Hospital from October 2018 and October 2019. We documented the clinical characteristics of patients, including tumor location, clinical stage, treatment, radiation dose, gross tumor volume (GTV), planning tumor volume (PTV) and Atkinson's Dysphagia score (ADS), and we recorded the nutrition status before radiation, including Patient-Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), weight loss percentage in 3 mouths (WL), the level of albumin (ALB), hemoglobin (HB), C-reactive protein (CRP) and Glasgow prognostic score (GPS). These factors were correlated with radiation esophagitis using univariate and multivariate regression analyses. RESULTS: Of 100 patients, 44% patients with PG-SGA score ≥9 at baseline, suggesting severe malnutrition, 41% patients developed grade ≥2 radiation esophagitis. In univariate analysis, dose >40 Gy (P=0.015), PTV ≥495 cm3 (P=0.049), PG-SGA score ≥9 (P=0.001), WL ≥10% (P=0.019) and ALB level <35 g/L (P=0.043) were significantly associated with grade ≥2 radiation esophagitis. Multivariate analysis revealed that PG-SGA score ≥9 (P=0.042) was the independent predictor of radiation esophagitis. CONCLUSIONS: Baseline nutritional status associated with development of grade ≥2 radiation esophagitis in patients with esophageal cancer undergoing radiotherapy.

Predictive value of EGF and uPAR for chemoradiotherapy response and survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy (CRT) plays a central role in the treatment of esophageal squamous cell carcinoma (ESCC). However, no effective biomarkers have been identified for predict CRT sensitivity and prognosis of patients with ESCC. The aim of this study was to investigate cytokine profiles of epidermal growth factor (EGF) and urokinase plasminogen activator receptor (uPAR) in 68 ESCC patients, and to evaluate the clinical utility of these markers. METHODS: This pilot study enrolled 68 patients who received neoadjuvant CRT followed by radical surgery or definitive CRT between 2015 and 2017. Serum specimen was obtained from each patient before treatment and at the time of administration of total doses of 40 Gy. Cytokines expression analyses were performed in pre- and post-treatment serum using human cytokine antibody arrays which contained 120 known tumor-related cytokines. RESULTS: Seven differentially expressed cytokines identified by cytokine antibody arrays in pre- and post-treatment serum from 4 patients with CRT sensitivity and 4 patients with CRT resistance. Of these, up-regulation of EGF and uPAR in serum at the doses of 40 Gy were associated with adverse clinical outcomes. The predictive value of EGF and uPAR were further assessed in a second set of 60 ESCCs. A total of 68 patients enrolled in this study. The median follow-up duration of these patients was 15.87 months (range, 6.21-23.85 months). Cox multivariate survival analyses revealed that high uPAR ratio after CRT independently predicted progression-free survival (PFS) (HR =3.999, 95% CI: 1.503-10.639, P=0.006) and patients with elevated levels of EGF after CRT exhibited significantly worse overall survival (OS) (HR =2.574, 95% CI: 1.046-6.335, P=0.040). Of note, uPAR expression was significantly positive correlation with EGF expression in pre- and post-treatment serum (P=0.0001, P=0.0038). Patients with both high EGF and uPAR ratios had an inferior PFS and OS, compared to patients with a high EGF ratio only or uPAR ratio only or neither (1-year PFS rate 44.2% vs. 61.4%, 1-year OS rate 64.2% vs. 83.4%, P=0.033 and 0.029, respectively). CONCLUSIONS: The levels of EGF and uPAR in serum are reliable and predictive biomarkers for survival in ESCC patients. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power. We present the following article in accordance with the REMARK reporting checklist.