Modification and application of sports rehabilitation materials based on conjugated materials.

Existing elastic band materials for sports rehabilitation equipment have some deficiencies in strength, flexibility and durability, and need to be further improved. Therefore, the aim of this paper is to modify elastic bands using a conjugated material, carbon nanotubes, to improve the strength, flexibility and durability of elastic bands. In this paper, conjugated carbon nanotubes were prepared, and their elastic bands were strengthened and toughened by solvent, dispersant and functionalizer respectively under tensile testing machine and scanning electron microscope. Then the application effect of elastic band modified by conjugated materials in exercise rehabilitation was analyzed experimentally. The experimental results show that the strength of the elastic bands modified with carbon nanotubes is in the optimal range for sports rehabilitation, and the elongation at break of the test elastic band toughness index was also higher than that before modification, all of which were more than 90%. The recovery time of the elastic band after modification was long; the elastic retention rate was high, and the deformation was not easy. The satisfaction rate of different grades of elastic bands after modification was particularly high, which was not less than 95%. The research and application of elastic band modification based on conjugated material carbon nanotubes is very important for training and treatment in sports rehabilitation, which can provide better support and stability.

Prognostic value of cranial radiotherapy and optimal timing stratified by lung-molGPA for NSCLC patients with brain metastases.

PURPOSE: The updated Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (lung-molGPA) index provide more accurate survival prediction for patients diagnose with advanced non-small cell lung cancer (NSCLC) with brain metastases (BM). Given that the value of cranial radiotherapy (CRT) is still controversial for NSCLC patients with BM, this retrospective study aimed to evaluate the value of CRT and optimal timing in NSCLC patients with initial BM after stratified with lung-molGPA index. METHODS: This study screened NSCLC patients with initial BM in our cancer center from February 2012 to July 2018. The prognosis value of CRT and optimal timing was evaluated with Kaplan-Meier survival analysis and the patients were classified into lung-molGPA0-2 and lung-molGPA2.5-4 group. Upfront CRT was defined as received CRT within 3 months after initial diagnosis and without BM progression, other CRT was classified into deferred CRT. RESULTS: Overall, 288 patients were enrolled in our study, 156 patients received CRT. The median follow-up time was 47 months. In the entire cohort, the median PFS and OS were 9.2 and 17.0 months, respectively. In the lung-molGPA2.5-4 group, CRT can bring significantly overall survival benefit for NSCLC patients with initial BM (HR: 0.48, 95% CI: 0.34-0.68, P < 0.0001), and the upfront CRT can further expand this survival benefits compared with deferred CRT (HR: 0.49, 95% CI: 0.27-0.89, P = 0.0026). But this phenomenon was not observed in lung-molGPA0-2 group patients. CONCLUSION: Upfront CRT could bring significantly overall survival benefit for these patients with lung-molGPA2.5-4 but not for patients with lung-molGPA0-2.

Multimodality MRI Radiomics Based on Machine Learning for Identifying True Tumor Recurrence and Treatment-Related Effects in Patients with Postoperative Glioma.

INTRODUCTION: Conventional magnetic resonance imaging (MRI) features have difficulty distinguishing glioma true tumor recurrence (TuR) from treatment-related effects (TrE). We aimed to develop a machine-learning model based on multimodality MRI radiomics to help improve the efficiency of identifying glioma TuR. METHODS: A total of 131 patients were enrolled and randomly divided into the training set (n = 91) and the test set (n = 40). Radiomic features were extracted from the postoperative enhancement (PoE) region and edema (ED) region from four routine MRI sequences. After analyses of Spearman's rank correlation coefficient, and least absolute shrinkage and selection operator, the key radiomic features were selected to construct support vector machine (SVM) and k-nearest neighbor (KNN) models. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to analyze the performance. RESULTS: The PoE model had a significantly higher area under curve (AUC) than the ED model (p < 0.05). Among the models constructed with a single sequence, the model using PoE regional features from CE-T1WI was superior to other models, with an AUC of 0.905 for SVM and 0.899 for KNN. In multimodality models, the PoE model outperformed the ED model with an AUC of 0.931 for SVM and 0.896 for KNN. The multimodality model, which combined routine sequences and the whole regional features, showed a slightly better performance with an AUC of 0.965 for SVM and 0.955 for KNN. Decision curve analysis showed the good clinical utility of multimodal radiomics models. CONCLUSIONS: Multimodality radiomics can identify glioma TuR and TrE, potentially aiding clinical decision-making for individualized treatment. And edematous regions may provide useful information for recognizing recurrence. RETROSPECTIVELY REGISTERED: 2021.04.15, No:2020039.

Tuftsin-tailored fusion protein inhibits the growth of circulating gastric tumor cells associated with macrophage phagocytosis.

Circulating tumor cells (CTCs) are a major cause of tumor metastasis and resistance to anticancer therapies. To date, no effective low-toxicity chemotherapeutic agents or antibodies have exhibited significant clinical activity against CTCs. Macrophages are important mediators of antitumor immunity. Tuftsin (TF), a tetrapeptide located at residues 289-292 of the CH2 domain of the Fc region of the IgG heavy chain, binds to Nrp-1, a receptor on the surface of macrophages that promotes phagocytosis and induces nonspecific activation of the immune system against tumors. Lidamycin (LDM) is an antitumor chemotherapy agent that is strongly cytotoxic to tumors and can dissociate into an apoprotein (LDP) and active enediyne (AE) in vitro. We previously constructed the fusion protein LDP-TF through genetic engineering and inserted the chromophore AE to produce LDM-TF, which can target macrophages to promote their phagocytic and cytotoxic activity against tumor cells. Preliminary experiments confirmed the anti-tumor activity of LDM-TFs. In this study, we found that LDM-TF effectively inhibited the growth of CTCs of gastric cancer origin and enhanced macrophage phagocytosis both in vivo and in vitro. Tumor cell expression of CD47, which helps to evade phagocytosis by macrophages, was substantially downregulated by LDM-TF. Notably, our in vitro experiments demonstrated that the combination of LDM-TF and anti-CD47 antibodies promoted phagocytosis more than either component alone. Our findings demonstrate the significant inhibitory effect of LDM-TF on the growth of CTCs of gastric cancer origin and suggest that the combination of LDM-TF and anti-CD47 antibodies may exhibit synergistic effects, thereby providing a new option for the clinical treatment of patients with advanced tumors that have metastasized.

An interpretable machine learning model for stroke recurrence in patients with symptomatic intracranial atherosclerotic arterial stenosis.

Background and objective: Symptomatic intracranial atherosclerotic stenosis (SICAS) is the most common etiology of ischemic stroke and one of the main causes of high stroke recurrence. The recurrence of stroke is closely related to the prognosis of ischemic stroke. This study aims to develop a machine learning model based on high-resolution vessel wall imaging (HR-VWI) to predict the risk of stroke recurrence in SICAS. Methods: This study retrospectively collected data from 180 SICAS stroke patients treated at the hospital between 2020.01 and 2022.01. Relevant imaging and clinical data were collected, and follow-up was conducted. The dataset was divided into a training set and a validation set in a ratio of 7:3. We employed the least absolute shrinkage and selection operator (LASSO) regression to perform a selection on the baseline data, laboratory tests, and neuroimaging data generated by HR-VWI scans collected from the training set. Finally, five machine learning techniques, including logistic regression model (LR), support vector machine (SVM), Gaussian naive Bayes (GNB), Complement naive Bayes (CNB), and k-nearest neighbors algorithm (kNN), were employed to develop a predictive model for stroke recurrence. Shapley Additive Explanation (SHAP) was used to provide visualization and interpretation for each patient. The model's effectiveness was evaluated using average accuracy, sensitivity, specificity, precision, f1 score, PR curve, calibration curve, and decision curve analysis. Results: LASSO analysis revealed that "history of hypertension," "homocysteine level," "NWI value," "stenosis rate," "intracranial hemorrhage," "positive remodeling," and "enhancement grade" were independent risk factors for stroke recurrence in SICAS patients. In 10-fold cross-validation, the area under the curve (AUC) ranged from 0.813 to 0.912 in ROC curve analysis. The area under the precision-recall curve (AUPRC) ranged from 0.655 to 0.833, with the Gaussian Naive Bayes (GNB) model exhibiting the best ability to predict stroke recurrence in SICAS. SHAP analysis provided interpretability for the machine learning model and revealed essential factors related to the risk of stroke recurrence in SICAS. Conclusion: A precise machine learning-based prediction model for stroke recurrence in SICAS has been established to assist clinical practitioners in making clinical decisions and implementing personalized treatment measures.

Fatal toxicity induced by anti-PD-1 immune checkpoint inhibitor in thymic epithelial tumor.

A standard treatment for advanced thymic epithelial tumors (TETs) after initial treatment remains unavailable to date. Targeted immune checkpoint inhibitors (ICIs) of the programmed cell death-1 (PD-1) pathway may produce objective responses in TETs, notably thymic carcinoma. Findings of clinical trials suggested ICIs are a practical choice. However, the risk of severe immuno-related adverse events is higher in TETs. Concerning histologic subtypes, thymomas are more frequently associated with autoimmune disorders than carcinomas, so close monitoring is needed for thymomas. In this article, we describe four cases of fatal toxicity caused by anti-PD-1 therapy in TETs. Four patients with metastatic thymomas or carcinoma difficult to treat with first-line standard chemotherapy were treated with the anti-PD-1 drug pembrolizumab or sintilimab. The association of PD-1 inhibitors with a high proportion of severe immuno-related adverse events in TETs necessitates attentive monitoring during treatment.

Thymic epithelial tumors are the most common malignancy of the anterior mediastinum in adults, with the occurrence of approximately 1.5 cases/million. Surgery is usually the treatment of choice. However, treatment options for advanced disease are poorly understood, and data are limited. Several studies have assessed the objective responses of immune checkpoint inhibitors in patients with advanced thymic epithelial tumors. Anti-cancer immunity also increases the risk of developing adverse events related to immunotherapy. Some patients can experience lethal toxicity. This article presents four cases of developing severe adverse events to exercise caution in prescribing these agents for thymic epithelial tumor, in particular thymoma.

Outcomes of first-line anti-PD-L1 blockades combined with brain radiotherapy for extensive-stage small-cell lung cancer with brain metastasis.

INTRODUCTION: Anti-programmed cell death-ligand 1 (Anti-PD-L1) blockades have become the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC) from CASPIAN and IMpower133 trials. SCLC has a high incidence of brain metastasis (BM) and brain radiotherapy (BRT) is the main local treatment method, but there is limited data on the BRT-immunotherapy scheme. The aim of the retrospective study is to investigate the clinical efficacy and safety of the first-line anti-PD-L1 blockades combined with BRT in ES-SCLC with BM. METHODS: Patients with newly diagnosed ES-SCLC with baseline BMs at Shandong Cancer Hospital and Research Institute between 2017 and 2021 were selected. Patients were divided into the anti-PD-L1+BRT group and BRT group. We also assessed the leukoencephalopathy in both groups. RESULTS: A total of 46 patients were selected. Fifteen were divided into anti-PD-L1+BRT group and 31 to BRT group. The median overall survival (OS) was not reached (NR) vs 15.9 m (P = 0.172). Progression-free survival (PFS) was numerically prolonged with anti-PD-L1 blockades, but the significance was not reached (median: 9.4 m vs 7.4 m, P = 0.362). The median intracranial PFS was not improved, neither (median: 8.2 m vs 8.9 m, P = 0.620). Objective response rate (ORR) in the two groups was 73.33% vs 77.42% (P = 0.949) and disease control rate (DCR) was both 100%. Intracranial ORR and DCR were 53.33% vs 70.97% (P = 0.239) and 73.33% vs 80.65% (P = 0.855), respectively. There was no significant difference in leukoencephalopathy incidence between the two groups. CONCLUSION: The combination of first-line anti-PD-L1 blockades with BRT did not confer a significant survival benefit in ES-SCLC with BM, without enhancing cranial neurotoxicity.

Radiation therapy for extensive-stage small-cell lung cancer in the era of immunotherapy.

Unlike non-small-cell lung cancer (NSCLC), the progression of small-cell lung cancer (SCLC) is slow. Extensive-stage SCLC (ES-SCLC) is a serious threat to human health, with a 5-year survival rate of <7%. Chemotherapy has been the first-line treatment for the past 30 years. The anti-PD-L1 checkpoint blockades durvalumab and atezolizumab have greatly prolonged overall survival and have become the standard first-line therapy for ES-SCLC since the CASPIAN and IMpower133 trials. In the era of chemotherapy, radiation therapy (RT), including thoracic radiation therapy (TRT) and brain radiation therapy (BRT), has shown clinical effects in randomized and retrospective studies on ES-SCLC. RT-immunotherapy has shown exciting synergistic effects in NSCLC. For ES-SCLC, the clinical effects of combining TRT/BRT with immunotherapy have not yet been systematically explored. In this review, we found that studies on RT-immunotherapy in ES-SCLC are relatively few and limited to early phase studies focusing on toxicity. The efficacy and safety profiles of early phase studies encourage prospective clinical trials. In this review, we discuss the best population, optimum TRT dose, proper TRT time, and strategies for reducing radiation-induced neurotoxicity. Furthermore, we suggest that biomarkers and patient performance status should be fully assessed before RT-immunotherapy treatment. Prospective trials are needed to provide more evidence for RT-immunotherapy applications in ES-SCLC.

Comprehensive Analysis and Validation of Competing Endogenous RNA Network and Tumor-infiltrating Immune Cells in Lung Adenocarcinoma.

OBJECTIVE: The potential pathogenesis of LUAD remains largely unknown. In the present study, we evaluated the competing endogenous RNA (ceRNA) regulatory network and tumorinfiltrating immune cells in LUAD. METHODS: We obtained the RNA profiles and corresponding clinical information of LUAD patients from the TCGA data portal, and identified differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) between LUAD samples and normal controls to build a ceRNA network. Additionally, the CIBERSORT algorithm was employed to analyze the patterns of immune cell infiltration. Then, two survival-predicting models were constructed based on the ceRNA network and tumor-infiltrating immune cells, which were validated by an independent GEO dataset GSE50081. Moreover, the correlation between prognosis-related ceRNAs and immune cells was also evaluated. RESULTS: In total, 484 LUAD samples and 59 normal controls were included in this study, and 15 DEmiRNAs, 94 DEmRNAs, and 7 DElncRNAs were integrated to construct the ceRNA network of LUAD. Meanwhile, differentially expressed tumor-infiltrating immune cells were also identified, and the expressions of monocytes and regulatory T cells were related to the overall survival (OS) of LUAD patients. Moreover, the prognostic prediction model based on ceRNA network or tumor-infiltrating immune cells exhibited significant power in predicting the survival of LUAD patients. Furthermore, co-expression analysis revealed that some prognosis-related ceRNAs, such as CCT6A, E2F7, SLC16A1, and SNHG3, were positively or negatively correlated with several tumorinfiltrating immune cells, such as monocytes and M1 macrophages. CONCLUSION: This study improves our understanding of the pathogenesis of LUAD and is helpful in exploring the potential therapeutic targets and prognostic biomarkers for LUAD.

Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell lung cancer: a retrospective analysis.

Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B + PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B + PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P < 0.001). The incidence of grade ⩾ 3 adverse events was higher in the B + PP group than in the PP group (27.3% vs. 10.8%, respectively; P = 0.204). Univariate and multivariate analyses suggested that the receipt of ⩾ 5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.

Therapeutic effect of osimertinib plus cranial radiotherapy compared to osimertinib alone in NSCLC patients with EGFR-activating mutations and brain metastases: a retrospective study.

BACKGROUND: The study aimed to compare the efficacy of osimertinib plus cranial radiotherapy (RT) with osimertinib alone in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations and brain metastases (BMs). METHODS: The clinical data of advanced NSCLC patients with BMs who received osimertinib were retrospectively collected. The patients were assigned to one of the two groups according to the therapeutic modality used: the osimertinib monotherapy group or the osimertinib plus RT group. RESULTS: This was a retrospective study and 61 patients were included from December 2015 to August 2020. Forty patients received osimertinib monotherapy, and twenty-one patients received osimertinib plus RT. Radiotherapy included whole-brain radiation therapy (WBRT, n = 14), WBRT with simultaneous integrated boost (WBRT-SIB, n = 5) and stereotactic radiosurgery (SRS, n = 2). The median number of prior systemic therapies in the two groups was one. Intracranial and systemic ORR and DCR were not significantly different between the two groups. No difference in iPFS was observed between the two groups (median iPFS: 16.67 vs. 13.50 months, P = 0.836). The median OS was 29.20 months in the osimertinib plus RT group compared with 26.13 months in the osimertinib group (HR = 0.895, P = 0.826). In the L858R mutational subgroup of 31 patients, the osimertinib plus RT group had a longer OS (P = 0.046). In the exon 19 deletion mutational subgroup of 30 patients, OS in the osimertinib alone group was longer than that in the osimertinib plus RT group (P = 0.011). The incidence of any-grade adverse events was not significantly different between the osimertinib plus RT group and the osimertinib alone group (47.6% vs. 32.5%, P = 0.762). However, six patients (28.5%) experienced leukoencephalopathy in the osimertinib plus RT group, and 50% (3/6) of the leukoencephalopathy was greater than or equal to grade 3. CONCLUSION: The therapeutic effect of osimertinib with RT was similar to that of osimertinib alone in EGFR-positive NSCLC patients with BM. However, for patients with the L858R mutation, osimertinib plus RT could provide more benefit than osimertinib alone.

The Role of Cytokines in Predicting the Response and Adverse Events Related to Immune Checkpoint Inhibitors.

Recently, the overall survival (OS) and progression-free survival (PFS) of patients with advanced cancer has been significantly improved due to the application of immune checkpoint inhibitors (ICIs). Low response rate and high occurrence of immune-related adverse events (irAEs) make urgently need for ideal predictive biomarkers to identity efficient population and guide treatment strategies. Cytokines are small soluble proteins with a wide range of biological activity that are secreted by activated immune cells or tumor cells and act as a bridge between innate immunity, infection, inflammation and cancer. Cytokines can be detected in peripheral blood and suitable for dynamic detection. During the era of ICIs, many studies investigated the role of cytokines in prediction of the efficiency and toxicity of ICIs. Herein, we review the relevant studies on TNF-α, IFN-γ, IL-6, IL-8, TGF-ß and other cytokines as biomarkers for predicting ICI-related reactions and adverse events, and explore the immunomodulatory mechanisms. Finally, the most important purpose of this review is to help identify predictors of ICI to screen patients who are most likely to benefit from immunotherapy.

Downregulation of lncRNA XR_429159.1 Linked to Brain Metastasis in Patients With Limited-Stage Small-Cell Lung Cancer.

Purpose: The purpose of this study was to identify aberrant long non-coding RNAs (lncRNAs) and explore the predictive value of lncRNA expression patterns on the risk of brain metastases (BMs) in patients with limited-stage small-cell lung cancer (SCLC). Patients and Methods: We executed an array of lncRNA and mRNA chip assays to examine the expression in peripheral blood mononuclear cells obtained from SCLC patients with BMs and compared the expression patterns against those from patients without BMs to identify lncRNAs associated with BMs. Validation was performed against clinical data to further confirm the relationship between lncRNAs and BM. Kaplan-Meier analysis was applied to estimate the cumulative incidence of BMs, and differences between the groups were analyzed using the log-rank test. Results: The expression of 67 lncRNAs (27 upregulated and 40 downregulated) and 47 mRNAs (20 upregulated and 27 downregulated) was significantly different between the BM and non-BM groups (fold change ≥ 2.0, p-value ≤ 0.05), based on the lncRNA and mRNA chip assays. Four lncRNAs were verified by quantitative real-time polymerase chain reaction (qRT-PCR) to confirm the accuracy of the microarray data, and the results of 11 patient pairs (11 patients with BM and 11 patients without BM) revealed that low LncRNA XR_429159.1 expression was a high-risk factor for BM. Further clinical data showed that the incidence of BM among 25 patients with low-level LncRNA XR_429159.1 expression was 31% at 1 year, compared with 14.3% among the 18 patients with high-level LncRNA XR_429159.1 expression (p = 0.035). Conclusion: Our present study identified the low-level expression of lncRNA XR_429159.1 as a high-risk factor among BM in patients with limited-stage SCLC. LncRNA XR_429159.1 is a critical molecule that regulates SCLC metastasis, involved in the neuroepithelial transforming gene 1 (NET1) pathway, and serum levels of this lncRNA are significantly associated with the risk of BM.

Estimating Survival in Patients with Non-Small-Cell Lung Cancer and Brain Metastases: A Verification of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA).

PURPOSE: A new tool based on clinical characteristics and molecular factors (Lung-molGPA) was developed to predict the survival of patients with non-small-cell lung cancer but was has not been validated. This study aims to validate the feasibility of the Lung-molGPA in NSCLC. PATIENTS AND METHODS: Patients diagnosed NSCLC between Feb 2012 and July 2018 were retrospectively reviewed and scored using the Lung-molGPA tool to compare clinical outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox regression analyses. RESULTS: A total of 618 patients (524 adenocarcinoma [ADC], 94 non-adenocarcinoma [non-ADC]) were collected. For all patients, the median survival time (MST) was 33.0 months (33.6 and 28 months in the ADC and non-ADC groups, respectively; p = 0.21). In the ADC group, the MST for patients with a Lung-molGPA score of 3.5 to 4 was more than 4 years, while the MST was only 25 months in patients scoring 0-1, 30.0 months in patients scoring 1.5-2, and 35.0 months for scores of 2.5-3 (p = 0.048). For the non-ADC group, the MST for scores 0-1, 1.5-2, 2.5-3, and 3.5-4 were 12.0, 20.2, 29.0, and 33.0 months, respectively (p = 0.017). CONCLUSION: Our findings provided evidence validating the Lung-molGPA score as a useful tool to determine treatment strategies and to predict prognosis. The model is still exploratory and needs to be evaluated further in combination with additional prognostic markers.

Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC.

Immune checkpoint blockades (ICBs) have changed the standard of care of squamous and adenocarcinoma non-small cell lung cancer (NSCLC). Whereas detailed researches regarding ICBs in the two major histological subtypes are rare. In order to uncover the clinical efficacy differences between squamous and adenocarcinoma NSCLC and better understand the underlying immune-regulatory mechanisms, we compared the survival benefits of ICBs between the two subtypes by revealing phase 3 randomized trials and attempted to uncover the immune-regulatory discrepancy. Generally, compared with nonsquamous NSCLC, squamous NSCLC benefited more from ICBs in Keynote 024, CheckMate 026, CheckMate 227 and CheckMate 017 and similar in OAK, but less in Keynote 010 and PACIFIC. We revealed that the tumor mutation burden (TMB) level, the programmed cell death ligand 1 (PD-L1) expression, tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME), chemokines, and oncogenic driver alterations within the two subtypes may contributed to the clinical outcomes of ICBs. We prospected that the combinations of ICBs with chemotherapy, radiation therapy, and antiangiogenic therapy could be promising strategies to re-immunize the less immunogenic tumors and further enhance the efficacy of ICBs.

Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer.

BACKGROUND: Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy has been approved as second-line or later therapy in advanced non-small-cell lung cancer (NSCLC). The study aimed to compare the clinical outcomes of PD-1 inhibitor plus chemotherapy with PD-1/PD-L1 inhibitor monotherapy as second-line or later therapy in advanced NSCLC. METHODS: The clinical data of patients with advanced NSCLC who received PD-1/PD-L1 inhibitors as second-line or later line therapy was retrospectively collected. Patients were assigned to one of the two groups according to the therapeutic modality used: PD-1/PD-L1 inhibitor monotherapy group or PD-1 inhibitor plus chemotherapy combination therapy group. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated between the two groups. The prognostic effect of the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) on the outcomes was also evaluated. RESULTS: From April 2017 to October 2019, a total of 84 patients were enrolled in the current study. Twenty-six patients (PD-1 inhibitor, n = 25; PD-L1 inhibitor, n = 1) received PD-1/PD-L1 inhibitor monotherapy, and fifty-eight patients received PD-1 inhibitor plus chemotherapy. The chemotherapy regimens used were as follows: liposome paclitaxel (n = 15); nab-paclitaxel (n = 12); docetaxel (n = 9); pemetrexed (n = 6); and others (n = 16). The DCR and OS were not significantly different between the two groups. The PFS of the monotherapy group was longer than that of the combination therapy group (mPFS: 9.6 vs. 4.6 months, P = 0.01). Univariate and multivariate analyses suggested that LDH and sex were independent prognostic factors of PFS. In the second-line therapy subgroup of 38 patients, OS and PFS were not significantly different between the two groups. In the subgroup of 46 patients treated beyond the 2nd line, the monotherapy group had a longer PFS (mPFS: 9.6 vs. 4.2 months, P = 0.01). The incidence of any-grade adverse events was not significantly different between the monotherapy group and the combination therapy group (19.2 vs. 18.9%, P = 1.000). One patient in the PD-1 inhibitor plus chemotherapy group died of immune-related pneumonitis. CONCLUSION: The clinical outcomes of PD-1 inhibitor plus chemotherapy as second-line or later therapy were similar to those of PD-1/PD-L1 inhibitor alone in advanced NSCLC.

The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients.

Immune checkpoint inhibitors (ICIs) are new and promising therapeutic agents for non-small cell lung cancer (NSCLC). However, along with demonstrating remarkable efficacy, ICIs can also trigger immune-related adverse events. Checkpoint inhibitor pneumonitis (CIP) has been reported to have a morbidity rate of 3% to 5% and a mortality rate of 10% to 17%. Moreover, the incidence of CIP in NSCLC is higher than that in other tumor types, reaching 7% to 13%. With the increased use of ICIs in NSCLC, CIP has drawn extensive attention from oncologists and cancer researchers. Identifying high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse events. In this review, the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease, prior thoracic irradiation, and combinations with other drugs. Our review also explored potential mechanisms closely related to CIP, including increased T cell activity against associated antigens in tumor and normal tissues, preexisting autoantibodies, and inflammatory cytokines.

MTAP-deficiency could predict better treatment response in advanced lung adenocarcinoma patients initially treated with pemetrexed-platinum chemotherapy and bevacizumab.

To investigate the predictive value of methylthioadenosine phosphorylase (MTAP) on treatment response and survival in advanced lung adenocarcinoma. MTAP expression was detected by immunohistochemistry. Treatment response and survival were compared according to MTAP expression level. The results indicated MTAP-low expression was observed in 61.2% (101/165) of all patients. The objective response rate and disease control rate improved in the MTAP-low group (64.4% vs 46.9%, p = 0.035; 92.1% vs. 79.7%, p = 0.03; respectively). The median progression-free survival and survival time in the MTAP-low group were significantly lower than that in the MTAP-high group (8.1 vs. 13.1 months, p = 0.002; 22 vs. 32 months, p = 0.044). Multivariate analysis demonstrated that brain metastasis (HR 1.55, p = 0.046), thoracic radiation (HR 0.52, p = 0.026), and MTAP-low expression (HR 1.36, p = 0.038) were independent factors on survival. It is concluded that MTAP-low expression could predict improved treatment response but worsened survival in advanced lung adenocarcinoma.

Bevacizumab in Combination with Pemetrexed and Platinum Significantly Improved the Clinical Outcome of Patients with Advanced Adenocarcinoma NSCLC and Brain Metastases.

BACKGROUND: The study aims to evaluate the clinical efficacy and safety of bevacizumab in combination with the first-line pemetrexed-platinum (PP) in patients with advanced adenocarcinoma non-small-cell lung cancer (NSCLC) and brain metastases. METHODS: The clinical data of patients with adenocarcinoma NSCLC and symptomatic or asymptomatic brain metastases were collected in our study. The basic chemotherapy regimen was pemetrexed-platinum (PP). According to whether combined with bevacizumab (B) or not, all enrolled patients were assigned to the B+PP group or the PP alone group. RESULTS: A total of 71 patients were enrolled in the current study. Twenty-six patients were allocated to the B+PP group and 45 were allocated to the PP group. Overall response rates (ORRs), disease control rates (DCRs) of the thoracic tumors and intracranial metastases and overall survival (OS) were not significantly different between the 2 groups. However, progression-free survival (PFS) and intracranial PFS (iPFS) were significantly prolonged in the B+PP group compared with the PP group. The median PFS was 9.2 and 8.2 months, and the 1-year PFS rates were 47.1% and 15.9%, respectively, in the 2 groups (P=0.029). And, the median iPFS were 24.3 and 10.9 months, and the 1-year iPFS rates were 80.1% and 40.1%, respectively, in the 2 groups (P=0.008). Univariate and multivariate analyses suggested that maintenance therapy and bevacizumab therapy were independent favorable prognostic factors of PFS and iPFS. CONCLUSION: The addition of bevacizumab to the first-line pemetrexed and platinum significantly improved clinical outcomes of patients with advanced adenocarcinoma NSCLC and brain metastases.

[Finite-element analysis of mandibular first molar with two marginal designs of endocrown for the repair of different defects].

OBJECTIVE: This study aimed to evaluate the stress distribution of the mandibular first molar with different thicknesses and heights of the axial wall restored by the endocrown with two marginal designs and thus provide a theoretical basis for selecting clinical preparation through the finite-element method. METHODS: Two marginal endocrowns of the mandibular first molar with different axial-wall thicknesses (t=1, 2, 3 mm) and heights (h=2, 3, 4 mm) were established. Group A was the butt-joint design, whereas group B was the shoulder-surrounded design. After applying vertical and oblique loads , the size and distribution of the maximum principal stress and equivalent stress of residual tooth tissue were recorded. RESULTS: The maximum principal stress and equivalent stress distribution of residual tooth tissue were similar among different models. Group A showed a lower maximum principal stress and equivalent stress than group B at the same thickness and height under vertical load. Meanwhile, under oblique load, the maximum principal stress values of groups A and B decreased with increased thickness at constant height. Group A showed lower equivalent stress than group B at the same thickness and height of 2 and 3 mm. However, when the height was 4 mm, the trend was reversed. CONCLUSIONS: In mastication, when bearing the vertical force, the retention of the butt-joint marginal endocrown preferred to the shoulder-surrounded one. Given the higher axial wall of the shoulder-surrounded marginal endocrown, it showed better ability to bear the oblique force than the butt-joint one.