Treatment patterns and clinical outcomes in 157 patients with extensive-stage small cell lung cancer: real-world evidence from a single-center retrospective study.

Background: Immune checkpoint inhibitors (ICIs) have changed the therapeutic options for extensive-stage small-cell lung cancer (ES-SCLC). In this real-world study, we analyzed the treatment patterns in patients with ES-SCLC and evaluated the efficacy of chemotherapy combined with immunotherapy as first-line therapy. Methods: A retrospective analysis was performed on patients with ES-SCLC who received treatment at China-Japan Friendship Hospital (Beijing, China) between August 1, 2020, and April 30, 2023. The treatment patterns appeared in the form of Sunburst Chart and Sankey diagram. The survival analyses were conducted by Kaplan-Meier curves. Results: A total of 157 patients with ES-SCLC were retrospectively included. According to first-line therapy, patients were divided into the chemotherapy (CT) group (n=82) and chemo-immunotherapy (CIT) group (n=75). The median treatment lines were 2[1, 2] and cycles were 8[5, 12], respectively. 82 patients received the second line of therapy, followed by 37 for the third, 15 for the fourth, 11 for the fifth, and 5 for the sixth. Overall, the treatment patterns involved 11 options including 12 chemotherapy regimens, 11 ICIs, and 4 targeted agents. The second-line treatment pattern had the most options (9) and regimens (43). In the first 3 lines, chemotherapy was the largest proportion of treatment options. The addition of ICIs prolonged progression-free survival from 6.77 (95% confidence interval [CI], 6.00-7.87) to 7.33 (95% CI, 6.03-9.80) months (hazard ratio [HR]=0.67, 95% CI, 0.47-0.95; P=0.025), overall survival from 12.97 (10.90-23.3) to 14.33 (12.67-NA) months without statistically significant difference (HR=0.86, 95% CI, 0.55-1.34; P=0.505). Conclusion: The treatment options of patients with ES-SCLC are more diversified. Combination therapy is the current trend, where chemotherapy is the cornerstone. Meanwhile, ICIs participate in almost all lines of treatment. However, the clinical efficacy remains barely satisfactory. We are urgently expecting more breakthrough therapies except immunology will be applied in the clinic.

Treatment-related adverse events of immune checkpoint inhibitors combined with angiogenesis inhibitors in advanced lung cancer: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) with angiogenesis inhibitors have been used to treat advanced lung cancer. Their associated treatment-related adverse events (trAEs) are currently considered acceptable; however, no conclusion has been reached. We aimed to summarize the trAEs caused by ICIs combined with angiogenesis inhibitors in patients with advanced lung cancer. METHODS: Pulled studies met the following criteria: patients with advanced lung cancer who received treatment involving ICIs combined with angiogenesis inhibitors (with or without chemotherapy) in interventional or observational studies. Results included the type and number of trAEs or immune-related adverse events (irAEs), treatment-associated discontinuation and mortality, overall survival (OS), and progression-free survival (PFS). PROSPERO: CRD42022337656. RESULTS: The study enrolled 32 trials involving 2313 patients who had 7768 any-grade trAEs and 1078 grade ≥3 trAEs. The pooled incidences were 87.33% (95% confidence interval [CI]: 79.49-93.65; I2 = 94.04%) for any-grade trAEs, and 38.63% (95% CI: 28.28-49.50; I2 = 95.61%) for grade ≥3 trAEs. There were 132 kinds of any-grade trAEs involving 18 systems, and 99 kinds of grade ≥3 trAEs involving 16 systems. For all trAEs, we observed significant differences in the line of therapy, trial design, therapy combination, and types of angiogenesis inhibitors (all P < 0.05). The rate of trAEs increased with dosage and frequency of medication. Pooled incidences of discontinuation and mortality were 10.64% and 0.81%, respectively. Nearly 647 patients experienced irAEs, including 636 any-grade irAEs and 154 grade ≥3 irAEs. CONCLUSIONS: Overall, the incidence of trAEs caused by ICIs combined with angiogenesis inhibitors is generally acceptable. These trAEs have a wide spectrum nearly covering the full range of adverse events. Grade ≥3 trAEs are more closely associated with angiogenesis inhibitors than any grade. However, treatment-associated mortality remains concerning.

Traditional Chinese medicine in the era of immune checkpoint inhibitor: theory, development, and future directions.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development.

Microsatellite instability-related prognostic risk score (MSI-pRS) defines a subset of lung squamous cell carcinoma (LUSC) patients with genomic instability and poor clinical outcome.

Background: Lung squamous cell carcinoma (LUSC) shares less typical onco-drivers and target resistance, but a high overall mutation rate and marked genomic complexity. Mismatch repair (MMR) deficiency leads to microsatellite instability (MSI) and genomic instability. MSI is not an ideal option for prognosis of LUSC, whereas its function deserves exploration. Method: MSI status was classified by MMR proteins using unsupervised clustering in the TCGA-LUSC dataset. The MSI score of each sample was determined by gene set variation analysis. Intersections of the differential expression genes and differential methylation probes were classified into functional modules by weighted gene co-expression network analysis. Least absolute shrinkage and selection operator regression and stepwise gene selection were performed for model downscaling. Results: Compared with the MSI-low (MSI-L) phenotype, MSI-high (MSI-H) displayed higher genomic instability. The MSI score was decreased from MSI-H to normal samples (MSI-H > MSI-L > normal). A total of 843 genes activated by hypomethylation and 430 genes silenced by hypermethylation in MSI-H tumors were classified into six functional modules. CCDC68, LYSMD1, RPS7, and CDK20 were used to construct MSI-related prognostic risk score (MSI-pRS). Low MSI-pRS was a protective prognostic factor in all cohorts (HR = 0.46, 0.47, 0.37; p-value = 7.57e-06, 0.009, 0.021). The model contains tumor stage, age, and MSI-pRS that showed good discrimination and calibration. Decision curve analyses indicated that microsatellite instability-related prognostic risk score added extra value to the prognosis. A low MSI-pRS was negatively correlated with genomic instability. LUSC with low MSI-pRS was associated with increased genomic instability and cold immunophenotype. Conclusion: MSI-pRS is a promising prognostic biomarker in LUSC as the substitute of MSI. Moreover, we first declared that LYSMD1 contributed to genomic instability of LUSC. Our findings provided new insights in the biomarker finder of LUSC.

Efficacy and Safety of Immune Checkpoint Inhibitors in Patients with Cancer and Hepatitis B or C: A Systematic Review and Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) have changed the situation of tumor therapy in recent years. However, for security reasons, those special populations are often excluded from clinical trials, such as infected hepatitis B or hepatitis C patients. ICIs are systematically reviewed and meta-analyzed for the first time in patients infected with hepatitis B or C in this paper. Methods: The relevant studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science until October 2022. Trials and observational studies meeting the inclusion criteria were included. The outcomes included the effectiveness of ICIs in patients with HBC/HCV (ORR, DCR, mOS, and mPFS), the incidence of adverse reactions, high-grade adverse reactions, and abnormal liver enzymes. At the same time, these indexes were compared with those of uninfected patients. Results: A total of 2,625 patients were enrolled, involving 1,179 patients with hepatitis (HBV or HCV). We found that ICIs showed higher ORR (25.80% vs. 18.10%) and DCR (66.22% vs. 58.74%) in patients with hepatitis B/C than those without infection. In terms of survival time, patients with hepatitis virus infection showed longer mOS (15.44 m vs. 13.30 m) but shorter mPFS (4.94 m vs. 5.01 m) than uninfected patients. As for safety data, patients with hepatitis showed a lower incidence of all-grade irAEs (68.02% vs. 70.43%) than uninfected patients, while that of 3-4 irAEs (21.27% vs. 21.79%) was similar in the two groups. However, hepatic dysfunction was more common and serious in hepatitis patients. Four HBVr and no HCVr were observed. Conclusion: According to this meta-analysis, ICIs are effective and safe for patients with hepatitis B or C, but basic liver enzymes have to be evaluated before treatment to avoid liver adverse events.

Long-term survival in extensive-stage small-cell lung cancer treated with different immune checkpoint inhibitors in multiple-line therapies: A case report and literature review.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, is highly prone to recurrence, and has a short survival period. It is very difficult to achieve long-term survival in ES-SCLC, which has not been significantly improved in the last 20 years. For a long time, platinum-based chemotherapy has occupied the core position in the treatment of small-cell lung cancer (SCLC), but there are few options for treatment drugs or regimens, and if disease progression occurs, the options for follow-up regimens are obviously limited. The advent of immunotherapy has changed this situation to some extent, and immunotherapy has shown some effects in improving efficiency and prolonging survival, whether in first- or third-line therapy, but it is still unsatisfactory. Case presentation: A 57-year-old patient with ES-SCLC experienced disease progression after four lines of treatment including synchronous radiotherapy, chemotherapy, and antiangiogenesis. However, the patient still benefited when switching to the programmed cell death receptor-1 (PD-1) inhibitor toripalimab in combination with chemotherapy in the fifth line. Even after the development of immune resistance, the patient still benefited after switching to tislelizumab in combination with different chemotherapy regimens or alone in the sixth and seventh lines. Following the progression of tislelizumab in combination with chemotherapy, the patient again profited after switching to durvalumab in combination with anlotinib and again achieved a progressive-free survival (PFS) of 11 months. Overall, the patient achieved a total of 45 months of PFS and 50 months of overall survival (OS), with a shocking and exciting 30 months of PFS achieved in the immune combination phase alone. Conclusion: We report a patient with ES-SCLC who achieved long-term survival after at least eight lines of therapy including chemotherapy, antiangiogenesis, and different immune checkpoint inhibitors (ICIs). This suggests that long-term survival in SCLC is possible with aggressive, combined, and standardized treatment. Otherwise, immunotherapy postline enablement can still benefit patients, rechallenge after immune resistance is also possible in SCLC, and combination with chemotherapy or antiangiogenic therapy can improve the efficacy and prolong the survival. This will provide new ideas and options for the selection of treatment options for SCLC.

Topical Zhiyang Pingfu Liquid for Moderate to Severe Skin Rash Associated With EGFRIs: A double-blinded randomized controlled trial.

BACKGROUND: Skin rash is the most common adverse effect associated with epidermal growth factor receptor inhibitors (EGFRIs). The study has observed the efficacy and safety of Zhiyang Pingfu Liquid in the treatment of EGFRIs-related moderate and severe rash. METHODS: Patients suffering from EGFRIs-related moderate to severe rash were enrolled and then randomly divided into the treatment group and the control group, receiving Zhiyang Pingfu Liquid and placebo liquid respectively combined with minocycline and methylprednisolone recommended by guideline for 14 days. Changes in rash grades were observed, as well as the dosage of minocycline. Blood routine examination and liver and kidney function were evaluated to observe the safety of Zhiyang Pingfu Liquid. The total response of rash included complete response (CR) and partial response (PR). And the effective rate of rash was the percentage of CR and PR in the total cases. RESULTS: A total of 54 out of 58 patients finished the study with 27 patients in each group. The effective rates of rash among the treatment group and the control group were 81.48% and 55.56% after 14 days treatment (P = .040). The treatment group had a lower dosage of minocycline compared with the control group. The median total dose of oral minocycline administration was 1000 mg in the treatment group and 1400 mg in the control group. CONCLUSION: Zhiyang Pingfu Liquid can effectively improve the moderate and severe EGFRIs-induced rash, and reduce the use of minocycline, as well as the side reactions brought by minocycline. However, larger randomized controlled trials are needed to verify these findings. CLINICAL TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry, the registration number is ChiCTR1800017053.

Changes of IL-6 And IFN-γ before and after the adverse events related to immune checkpoint inhibitors: A retrospective study.

Immune checkpoint inhibitors (ICIs) have changed the status of tumor immunotherapy. ICIs-related adverse events (irAEs) have the high incidence and are difficult to predict and prevent. Researches have suggested that changes of cytokines were associated with irAEs. This study focused on the changes of interleukin-6 (IL-6) and interferon-γ in patients before and after irAEs and trying to find the biomarkers of irAEs. Collect basic data of patients who were treated with ICIs in China-Japan Friendship Hospital from January 2017 to August 2021 and had irAEs. Make statistics on IL-6 and INF-γ in the blood before and after irAEs. A total of 10 patients were enrolled, including 7 males and 3 females. According to statistical analysis, the IL-6 concentration level after irAEs was significantly higher than before, and the difference was statistically significant (P = .023); the interferon-γ concentration level was not changed significantly from before, the difference was not statistically significant (P = .853). The elevation of IL-6 was associated with the occurrence of adverse reactions in ICIs.

Radiation induced lung injury (RILI) after postoperative intensity modulated proton therapy (IMPT) in a patient with stage III locally advanced lung adenocarcinoma: a case report.

Background: Postoperative radiation therapy (PORT) remains the critical therapy for stage III non-small cell lung cancer (NSCLC). Radiation induced lung injury (RILI) is common and affects the clinical outcome. Proton therapy (PT) is a new-style radiotherapy with accurate distribution of curative dose to tumor and increased organ-at-risk (OAR) sparing, which potentially decrease the incidence of RILI. Intensity modulated proton therapy (IMPT) is more flexible and conformal one. Case Description: In the case, we report a 47-year-old man with stage III locally advanced lung adenocarcinoma developing RILI after IMPT. The man had no chronic pulmonary disease before. After 6 cycles every three-week of postoperative adjuvant chemotherapy (pemetrexed, carboplatin), he sequentially received 50 GyE of IMPT in 25 fractions. About 7 weeks after IMPT, grade 2 RILI was developed with the manifestation of focal pulmonary consolidation and ground-glass attenuation. Steroid therapy was delivered and the pneumonias absorbed slightly with chronic scarring and fibrosis left over. Conclusions: RILI after IMPT is not commonplace especially under the circumstance where the patient had no chronic lung disease and the proton dose was conservative. The patient manifested as the early developed acute exudation and fibrosis stage. Moreover, the injury was so refractory that fibrosis was developing in spite of active steroid therapy. Based on the case, we suggested that more exploration of proton induced lung injury and evaluation before IMPT especially following chemotherapy are deserved.

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Immunotherapies represented by immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. A large part of the population has both cancer and psoriasis but is usually excluded from ICI clinical trials because of the dysregulated activation of the immune system. This is the first study to evaluate the safety and efficacy of ICI therapy in patients with cancer and preexisting psoriasis. Methods: PubMed, EMBASE, Cochrane, and MEDLINE databases were searched from inception through February 2022. Observational studies on patients with cancer and confirmed psoriasis before ICI initiation were included. Outcomes included the incidence of psoriasis flares, de novo immune-related adverse events (irAEs), discontinuation rate due to flare/de novo irAEs, and efficacy of ICI therapy. Clinical manifestations, management, and outcomes for adverse events (AEs) were systematically reviewed. All pooled analyses were based on a random-effects model using Stata software. Meta-regression and subgroup analyses were performed to identify sources of heterogeneity. Results: Twelve studies involving 191 patients were included. The pooled incidence of psoriasis flares was 45.0% (95% CI: 31.1%-58.9%, I2 = 71.7%) and 44.9% (95% CI: 29.0%-60.7%, I2 = 71.8%) for de novo irAEs. The tumor type, psoriasis subtype, ICI class, and country were the main sources of heterogeneity. Grade 3-4 flares occurred in 10.8% (95% CI: 5.3%-16.3%) of patients, and about 16.6% (95% CI: 10.7%-22.5%) of patients experienced grade 3-4 de novo irAEs. The estimated incidence of ICI discontinuation due to AE was 18.5% (95% CI: 6.1%-30.8%, I2 = 68.7%). The median times to develop flare and de novo irAEs were 44 and 63 days, respectively. Endocrinopathies and colitis were the most common de novo irAEs. Conventional therapy is effective for most AEs. The estimated objective response rate (ORR) of ICIs was 38.1% (95% CI: 11.8%-64.3%, I2 = 81.7%), and the disease control rate (DCR) was 64.5% (95% CI: 55.3%-73.8%, I2 = 0). Conclusions: The flare of patients with cancer and preexisting psoriasis treated with ICI therapy is frequent, but the incidence of de novo irAEs and the efficacy of ICI therapy are comparable to those of the general population. Most AEs are mild and manageable with conventional therapy, which required discontinuation of ICI therapy in 18.5%. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022320646.

Neoadjuvant Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related death worldwide. A meta-analysis was conducted to assess the benefits and risks of neoadjuvant immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Online databases, including PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, were retrospectively and systematically searched for eligible trials from database inception to May 2021. A total of 792 patients from 21 clinical trials were included. For surgical data, the pooled operation rate and R0 resection rate were 92% (95% CI 87-96%) and 97% (95% CI 94-99%). Additionally, neoadjuvant ICIs achieved a major pathological response (MPR) of 39% (95% CI 25-53%), including 25% (95% CI 16-36%) pathological complete response (pCR). With radiological response assessment, the pooled objective response rate (ORR) and disease control rate (DCR) were 44% (95% CI 21-68%) and 88% (95% CI 75-98%), respectively. In terms of safety, the pooled rate of any-grade and grade 3-5 treatment-related adverse effects (TRAEs) were 57% (95% CI 38-76%) and 15% (95% CI 6-28%). Eventually, the study concludes that neoadjuvant ICIs are effective and safe for patients with early-stage NSCLC. Key Words: Neoadjuvant therapy, Immune checkpoint inhibitors, Non-small cell lung cancer, Meta-analysis.

Hyper-Methylated Hub Genes of T-Cell Receptor Signaling Predict a Poor Clinical Outcome in Lung Adenocarcinoma.

Background: Immune checkpoint inhibitors (ICIs) emerge as the first-line treatment of lung adenocarcinoma (LUAD); selection of subpopulations acquiring clinical benefit is required. Associations between epigenetic modulation of tumor microenvironment (TME) and clinical outcome are far from clear. We focused on immune-related genes closely regulated by DNA methylation to identify the potential clinical outcome indicators. Methods: We systematically calculated immunophenotype score (IMpS) and classified immunophenotypes based on seven TME features in three independent cohorts. The overlapping of differential expressed genes and methylated probes targeted genes was regarded as genes closely regulated by DNA methylation. Then, probe/gene pairs which highly correlated with each other and IMpS were identified and named as immune-related probe/gene pairs (mIMg). Prognostic mIMg were selected and verified in seven independent validation cohorts. Results: Three immune phenotypes were clustered, and similar results were obtained in the three independent training cohorts. C2 displayed as an immunologically hot phenotype, whereas C3 corresponded with immunologically cold phenotype. Average methylation level was decreased from C2 to C3 (C2 > C1 > C3). Similarly, ICIs nonresponders showed global hypo-methylation compared with responders. Genes in mIMg were mainly enriched, especially in T-cell receptor activation, and repressed in noninflamed TME by hyper-methylation. Among mIMg, low expression and hyper-methylation of CD247, LCK, and PSTPIP1 were risk factors of overall survival (OS). ICIs nonresponders were more likely to be hyper-methylated in the three genes. By integrating with the oncogenes status, we demonstrated that EGFR wt and SRGN overexpressed patients were associated with chronic inflammation and immune evasion, showing an immunologically hot phenotype, which might lead to the short OS but derive clinical benefit from ICIs. Conclusions: This study identifies hyper-methylation and concurrent repression of CD247, LCK, PSTPIP1 as immune negative indicators and risk factors for prognosis in LUAD. Moreover, EGFR/SRGN axis may participate in immune modification to influence ICIs response and clinical outcome in LUAD.

A Single-Arm Phase II Study to Evaluate Efficacy and Safety of First-Line Treatment With DCVAC/LuCa, Standard of Care Chemotherapy and Shenqi Fuzheng Injection in Advanced (Stage IIIB/IV) Non-Small Cell Lung Cancer Patients.

OBJECTIVES: To evaluate the efficacy and safety of first-line treatment with a dendritic cell vaccination for lung cancer (DCVAC/LuCa), standard of care chemotherapy and Shenqi Fuzheng injection in patients with advanced (stage IIIB/IV) non-small cell lung cancer. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed recurrent metastatic or advanced NSCLC (stage IIIB/IV) with wild-type epidermal growth factor receptor (EGFR) or EGFR mutation which does not confer increased tumor susceptibility to EGFR-interacting drugs were recruited. For the treatment period, the first cycle of standard of care therapy (SoC) started 2 to 14 days after the leukapheresis procedure. SoC continued 4 to 6 cycles. DCVAC/LuCa was administered from the second cycle of SoC. DCVAC/LuCa was administered in a 3-week cycle schedule (5 doses) and then in a 6-week cycle schedule. Shenqi Fuzheng injection was administered 3 days before each DCVAC/LuCa administration for a total of 14 daily doses. Patients would undergo disease evaluation by computed tomography (CT) scan every 3 months. The primary and secondary endpoint was efficacy with regard to objective response rate (ORR) and progression free survival (PFS). The safety profile was measured by: incidence, type, and severity of all adverse events (AEs), laboratory abnormalities (blood routine test, urine test, and chemical test), physical status, and vital signs. Qi insufficiency was evaluated by tongue diagnosis and questionnaire survey with "Classification and Determination of constitution in TCM." RESULTS: Twenty-three patients from 3 hospitals who received combination therapy were included. ORR was 34.8% (95% CI:16.4%-57.3%). Median duration of response was 5.51 m (95% CI:2.70-8.32). Median PFS was 10.72 m (95% CI:4.52-16.93), 1-year survival was 77.8%. mOS was 21.97 m (95% CI:13.68-30.25). There was 1 severe AE related to a history of heart disease and there were no adverse events related to DCVAC/LuCa treatment. Qi insufficiency was improved significantly (P < .0001) from 41.19 ± 14.58 before treatment to 10.52 ± 16.58 after treatment. CONCLUSION: DCVAC/LuCa, combined with standard of care chemotherapy and Shenqi Fuzheng injection exhibited good benefit in Chinese patients with recurrent metastatic or advanced (stage IIIB/IV) NSCLC, and also significantly improved Qi insufficiency constitution. There were no related adverse events with DCVAC/LuCa treatment.

mRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development.

Homozygous mutations in the gene encoding the scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability. Intellectual disability is associated with both abnormal neocortical development and mRNA metabolism. However, the role of DcpS and its scavenger decapping activity in neuronal development is unknown. Here, we show that human neurons derived from patients with a DcpS mutation have compromised differentiation and neurite outgrowth. Moreover, in the developing mouse neocortex, DcpS is required for the radial migration, polarity, neurite outgrowth, and identity of developing glutamatergic neurons. Collectively, these findings demonstrate that the scavenger mRNA decapping activity contributes to multiple pivotal roles in neural development and further corroborate that mRNA metabolism and neocortical pathologies are associated with intellectual disability.

Catalyst Design for Electrochemical Reduction of CO2 to Multicarbon Products.

Electrochemical reduction of CO2 (CO2 RR), driven by renewable energy (such as wind and solar energy), is an effective route toward carbon neutralization. The multicarbon (C2+ ) products from CO2 RR are highly desirable, since they are important fuels, chemicals, and industrial raw materials. However, selective reduction of CO2 to C2+ products is especially challenging, due to low selectivity, poor yield, and high overpotential. Since the performance of CO2 RR is closely related to the structure and composition of catalysts, which alter the binding energy of intermediates generated in CO2 RR, it is necessary to study these effects systematically to achieve possible design strategies. Herein, design strategies toward catalysts for CO2 conversion to C2+ products are discussed on the basis of the adjustment of the structure and composition of catalysts, such as morphology control, defect engineering, bimetal, and surface modification. Meanwhile the reaction mechanisms and structure evolution of catalysts during CO2 RR are focused on in particular. Finally, challenges and perspectives are proposed for further improvement of CO2 RR technologies.

Association Between Efficacy of Immune Checkpoint Inhibitors and Sex: An Updated Meta-Analysis on 21 Trials and 12,675 Non-Small Cell Lung Cancer Patients.

BACKGROUND: Mounting randomized clinical trials have proved that immune checkpoint inhibitors (ICIs) achieved better overall survival (OS) and progression-free survival (PFS) than chemotherapy drugs for advanced non-small cell lung cancer (NSCLC) patients. However, some literatures have indicated that different sexes might not have equal immune response. Also, no agreement reached on the issue whether therapeutic benefit of ICIs is related to sex. OBJECTIVES: To explore the association between efficacy of ICIs for NSCLC patients and their sexes and summarize overall treatment-related adverse events (TRAEs) in an exploratory manner. METHODS: We performed this systematic review and meta-analysis of all potentially relevant studies retrieved from PubMed, EMBASE, and the Cochrane Library until June 2021, for eligible randomized controlled trials (RCTs) comparing immunotherapy with chemotherapy in advanced NSCLC patients. Literature screening, summary data extraction was performed independently and in duplicate. The pooled hazard ratio (HR) and 95% confidence interval (CI) of OS, PFS and TRAEs were calculated, applying STATA software and random-effects models. This study was registered in international prospective register of systematic reviews (PROSPERO), number CRD42020210797. RESULTS: Twenty-one trials involving 12,675 NSCLC patients were included. For patients with advanced NSCLC, ICIs significantly prolonged the OS (males: HR 0.73, 95%CI 0.67-0.79; females: HR 0.73, 95%CI 0.61-0.85) and PFS (males: HR 0.62, 95%CI 0.55-0.70; females: HR 0.68, 95%CI 0.55-0.81) versus chemotherapy. Overall, there was no statistical difference between their sexes (OS: P = 0.97; PFS: P = 0.43), respectively. Owing to insufficient TRAEs data of different sexes, we only found immunotherapy for NSCLC patients had more all-grades (RR 0.88; 95%CI 0.82-0.95) and 3-5 grades (RR 0.60; 95%CI 0.47-0.75) AEs compared with chemotherapy. CONCLUSION: Our findings indicated that the interaction between immunotherapy efficacy and different sexes was equally evident. Overall, patients with NSCLC could obtain more benefits from ICIs than chemotherapy regimen regardless of their sexes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020210797.

Immune-Related Multiple-Organs Injuries Following ICI Treatment With Tislelizumab in an Advanced Non-Small Cell Lung Cancer Patient: A Case Report.

Immune-related adverse events (irAEs) following treatment with immune checkpoint inhibitors (ICIs) can affect almost any organ systems. Multiple-organs irAEs are a rare occurrence which makes its management and treatment very challenging. This is a case report of a 71-year-old man with advanced non-small cell lung cancer (NSCLC) who developed multiple-organs irAEs (lung, muscle, myocardium, liver, and pituitary) after a single cycle (21 days) of the BGB-A317 (Tislelizumab). After more than two months of immunosuppression treatment with glucocorticoids, the tumor and inflammatory lesions in the lung were reduced. The levels of serum creatase, cardiac troponin T (TNT), and hepatic transaminase were also reduced. Four months after the termination of ICI therapy, the lung tumor reappeared in the previous site. This rare case report supplies several experiences in the management of multiple-organs irAEs, including full-scale monitoring of immunological indicators, early differential diagnosis, and prompt glucocorticoid therapy. This patient was not a candidate for the ICI re-challenge therapy due to the number and seriousness of irAEs. Multiple-organs irAEs add complexity to the management, and additional research is needed to develop optimal therapeutic guidelines.

The incidence of pseudoprogressive disease associated with programmed cell death 1/programmed cell death ligand 1 inhibitors: A meta-analysis.

BACKGROUND: The method to evaluate the efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors has become a big concern for researchers with its widely application. Pseudoprogressive disease (PPD) makes this process more difficult, which means that the tumor progressed at the initial evaluation, but re-evaluation after continued treatment suggested that the treatment was effective. However, PPD has not attracted enough attention of clinical doctors. This article is to systematically evaluate the incidence of PPD associated with PD-1/PD-L1 inhibitors with meta-analysis, to provide guidance for the recognition and management of PPD. METHODS: The databases of PubMed, EMBase, Cochrane Library were retrieved from the earliest collection date of the databases until Dec 5, 2019. The search terms of "pseudoprogressive disease, anti-PD-1, anti-PD-L1, PD-1/PD-L1 inhibitor, etc" were used for logistic combination search. Published studies on PPD caused by PD-1/PD-L1 inhibitors were included. Meta-analysis was performed with Stata 15.1. Subgroup analysis was performed according to the study population, tumor type, and evaluation criteria for efficacy. RESULTS: Seven researches, including 1458 patients were taken into the study. Meta-analysis showed that the overall incidence of PPD was 3.70% (95% confidence interval [CI]: 2.70%, 4.90%). Subgroup analysis showed that the incidence of PPD was 3.30% (95% CI: 1.90%, 5.90%) in non-small cell lung cancer patients and 5.10% (95% CI: 2.30%, 11.6%) in melanoma patients. There was no statistically significant difference between East and West populations and among various efficacy evaluation criteria. CONCLUSION: The incidence of PPD related to PD-1/PD-L1 inhibitors is not high, but the evaluation criteria has not yet been unified. Close monitoring, careful identification and proper application should be carried out in the clinic, and full management of the treatment with PD-1/PD-L1 inhibitors should be well done.