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.

Inhibition of Aurora A enhances radiosensitivity in selected lung cancer cell lines.

BACKGROUND: In mammalian cells, Aurora serine/threonine kinases (Aurora A, B, and C) are expressed in a cell cycle-dependent fashion as key mitotic regulators required for the maintenance of chromosomal stability. Aurora-A (AURKA) has been proven to be an oncogene in a variety of cancers; however, whether its expression relates to patient survival and the association with radiotherapy remains unclear in non-small cell lung cancer (NSCLC). METHODS: Here, we first analyzed AURKA expression in 63 NSCLC tumor samples by immunohistochemistry (IHC) and used an MTS assay to compare cell survival by targeting AURKA with MLN8237 (Alisertib) in H460 and HCC2429 (P53-competent), and H1299 (P53-deficient) cell lines. The radiosensitivity of MLN8237 was further evaluated by clonogenic assay. Finally, we examined the effect of combining radiation and AURKA inhibition in vivo with a xenograft model and explored the potential mechanism. RESULTS: We found that increased AURKA expression correlated with decreased time to progression and overall survival (p = 0.0447 and 0.0096, respectively). AURKA inhibition using 100 nM MLN8237 for 48 h decreases cell growth in a partially P53-dependent manner, and the survival rates of H460, HCC2429, and H1299 cells were 56, 50, and 77%, respectively. In addition, the survival of H1299 cells decreased 27% after ectopic restoration of P53 expression, and the radiotherapy enhancement was also influenced by P53 expression (DER H460 = 1.33; HCC2429 = 1.35; H1299 = 1.02). Furthermore, tumor growth of H460 was delayed significantly in a subcutaneous mouse model exposed to both MLN8237 and radiation. CONCLUSIONS: Taken together, our results confirmed that the expression of AURKA correlated with decreased NSCLC patient survival, and it might be a promising inhibition target when combined with radiotherapy, especially for P53-competent lung cancer cells. Modulation of P53 function could provide a new option for reversing cell resistance to the AURKA inhibitor MLN8237, which deserves further investigation.

[Value of E-PASS and mE-PASS in predicting morbidity and mortality of gastric cancer surgery].

OBJECTIVE: To investigate the clinical value of Physiologic Ability and Surgical Stress (E-PASS) and modified Estimation of Physiologic Ability and Surgical Stress (mE-PASS) scoring systems in predicting the mortality and surgical risk of gastric cancer patients, and to analyze the relationship between the parameters of E-PASS and early postoperative complications. METHODS: Clinical data of 778 gastric cancer patients who underwent elective surgical resection in Tianjin Medical University General Hospital from Jan. 2010 to Jan. 2014 were analyzed retrospectively. E-PASS and mE-PASS scoring systems were used to predict the mortality of gastric cancer patients, respectively. Univariate and unconditioned logistic regression analyses were performed to assess the relationships between nine parameters of E-PASS system and early postoperative complications. RESULTS: E-PASS and mE-PASS systems were used to predict the mortality in the death group and non-death group. The Z value was -5.067 and -4.492, respectively, showing a significant difference between the two groups (P<0.05). AUCs of mortality predicted by E-PASS and mE-PASS were 0.926 and 0.878 (P>0.05), and the prediction calibration of postoperative mortality showed statistically non-significant difference (P>0.05) between the E-PASS and mE-PASS prediction and actual mortality. Univariate analysis showed that age, operation time, severe heart disease, severe lung disease, diabetes mellitus, physical state index and ASA classification score are related to postoperative complications (P<0.05 for all). Unconditioned logistic regression analysis showed that severe lung disease, diabetes mellitus, ASA classification score and operation time are risk factors for early postoperative complications (P<0.05 for all). CONCLUSIONS: Both mE-PASS and E-PASS scoring system have good consistency in the predicting postoperative mortality and actual mortality, and both are suitable for clinical application. Moreover, the mE-PASS scoring system is clinically more simple and convenient than E-PASS scoring system. Preoperative severe lung disease, diabetes mellitus, ASA classification score and operation time are independent factors affecting the early postoperative complications.

[Prognostic value of combined expression of Aurora A, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer].

OBJECTIVE: The aim of this study was to investigate the prognostic value of combined expression of Aurora A, Ki-67, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer (NSCLC). METHODS: Expressions of Aurora A, Ki-67, p53 and p21 WAF1 in 58 tumor samples from resected primary NSCLCs were detected by immunohistochemistry. The correlation of proteins, survival and clinicopathological characteristics was analyzed. RESULTS: The positive rates of Aurora A, Ki-67, p53 and p21 WAF1 expression were 89.7% (52/58), 53.4% (31/58), 46.6% (27/58) and 34.5% (20/58), respectively. Aurora A expression was positively correlated with nodal metastasis (69.2% vs. 37.8%, P = 0.045). The univariable analysis showed that the overall survival (OS) was 75.0%in patients with low Aurora A expression and 46.0% in patients with high Aurora A expression (P = 0.039). The 3-year survival rate was 40.0% in patients with positive expression of Aurora A and p53, 65.0% in the patients with positive expression of Aurora A or p53, and 82.1% in the patients with negative expression of Aurora A and p53 (P = 0.039). The Cox regression model showed that combined expression of Aurora and p53 is an independent factor affecting the prognosis of NSCLC patients (P = 0.015). CONCLUSIONS: Our findings suggest that the positive expression of Aurora A, Ki-67 and p53 proteins is an unfavorable factor affecting the prognosis for NSCLC patients, and the overexpression of Aurora A is an independent unfavorable factor association with shorter OS in NSCLC patients. Detection of positive Aurora A and p53 expression may be a useful predictive prognostic indicator for NSCLC patients.

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.

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.

PTTG1 promotes migration and invasion of human non-small cell lung cancer cells and is modulated by miR-186.

Deeper mechanistic understanding of non-small cell lung cancer (NSCLC), a leading cause of total cancer-related deaths, may facilitate the establishment of more effective therapeutic strategies. In this study, pituitary tumor transforming gene (PTTG1) expression was associated with lymph node and distant metastasis in patients with NSCLC and was correlated with patient survival. Reduction of PTTG1 by small interfering RNA (siRNA) inhibits the migration and invasion of NSCLC cells by mediating matrix metalloproteinases expression. To the best of our knowledge, this study is the first to report that PTTG1 promotes epidermal growth factor (EGF) induced the phosphorylation of LIN-11, Isl1 and MEC-3 protein domain kinase and cofilin, a critical step in cofilin recycling and actin polymerization. Additionally, EGF-induced Akt phosphorylation was suppressed through knockdown of PTTG1. Interestingly, miR-186 can modulate PTTG1 protein expression. As observed from the animal experiment in this study, knockdown of PTTG1 through siRNA and overexpression of miR-186 inhibited invasive activity of NSCLC cells toward the SCID mice lung. In summary, our in vitro and in vivo results indicate that PTTG1 modulated by miR-186 has an important function in NSCLC invasion/metastasis. This study identified both PTTG1 and miR-186 as potential anti-invasion targets for therapeutic intervention in NSCLC.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.