Prognostic impact of age in advanced non-small cell lung cancer patients undergoing first-line checkpoint inhibitor immunotherapy and chemotherapy treatment.

BACKGROUND: Research on the association between age and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy combined with chemotherapy as first-line setting is limited. The aim of study is to determine the influence of age on the progress-free survival (PFS) and overall survival (OS) in those patients after adjusting for potential confounders. METHODS: A total of 207 advanced NSCLC patients treated with immunotherapy combined with chemotherapy in the first-line treatment in Guangxi Medical University Cancer Hospital from March 10, 2019, to December 31, 2022, was retrospectively analyzed. χ2 (categorical variables) was used to analyze the differences among the different age groups. Cox regression and Kaplan-Meier analyses were used to assess the association between age and clinical outcomes. P values < 0.05 (two-sided) were considered statistically significant. RESULTS: The mean age of the cohort was 58.8 ± 10.3 years. The percentages of patients < 65, 65-69, 70-74, and ≥ 75 years were 66.7 %, 19.3 %, 9.2 % and 4.8 %, respectively. Compared to the aged < 65 years group, the HR for the risk of disease progression for each group are 0.67 (95 %CI = 0.40-1.12, P = 0.125), 0.66 (95 %CI = 0.31, 1.43, P = 0.298), and 2.27 (95 %CI = 0.80, 6.45, P = 0.124), respectively, with no significant differences in the results. And the HR for risk of death for the 65-69 years and 70-74 years groups was 1.16 (95 %CI = 0.64-2.08, P = 0.628) and 0.93 (95 %CI = 0.39-2.23, P = 0.879), respectively. The difference has no statistical significance. Whereas in patients aged ≥ 75, there is an increased risk of death after adjusted confounders with HR = 4.83 (95 %CI = 2.06-11.35). The difference was statistically significant (P < 0.001). Trend test indicates that with advancing age, the patient's risk of death increases (HR = 1.33, 95 % CI = 1.02-1.75, P = 0.034). CONCLUSION: Age may not be the primary factor influencing the efficacy of immunotherapy combined with chemotherapy, but particular attention should be given to the elderly population.

Impact of liver metastases status on survival outcomes of first-line immunotherapy in extensive stage small cell lung cancer: a systematic review and meta-analysis.

PURPOSE: This study aims to assess the impact of liver metastases status on survival outcomes of first-line immunotherapy in extensive stage small cell lung cancer (ES-SCLC) patients. MATERIALS AND METHODS: Comprehensive searches were conducted in the Cochrane Library databases, Embase, PubMed, and abstracts from WCLC, ESMO, and ASCO from inception to December 2022. Randomized controlled trials reporting progression-free survival (PFS) and/or overall survival (OS) of first-line immunotherapy in ES-SCLC patients were included. RESULTS: Six trials involving 3501 patients were analyzed, comprising 1350 patients with liver metastases and 2151 without. The quality of the included trials was consistently high. Pooled results revealed that immunotherapy plus chemotherapy did not significantly improve PFS (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.68-1.00, P = 0.05) and OS (HR = 0.89, 95% CI: 0.79-1.00, P = 0.05) in ES-SCLC patients with liver metastases compared to chemotherapy alone. However, immunotherapy plus chemotherapy improved PFS (HR = 0.66, 95% CI: 0.57-0.77, P < 0.01) and OS (HR = 0.74, 95% CI: 0.67-0.82, P < 0.01) in ES-SCLC patients without liver metastases compared to chemotherapy alone. CONCLUSIONS: First-line immunotherapy plus chemotherapy significantly improved PFS and OS in ES-SCLC patients without liver metastases compared to chemotherapy alone. However, patients with liver metastases did not experience comparable benefits.

Bioorthogonal Microbubbles with Antifouling Nanofilm for Instant and Suspended Enrichment of Circulating Tumor Cells.

Integrating clinical rare cell enrichment, culture, and single-cell phenotypic profiling is currently hampered by the lack of competent technologies, which typically suffer from weak cell-interface collision affinity, strong nonspecific adsorption, and the potential uptake. Here, we report cells-on-a-bubble, a bioinspired, self-powered bioorthogonal microbubble (click bubble) that leverages a clickable antifouling nanointerface and a DNA-assembled sucker-like polyvalent cell surface, to enable instant and suspended isolation of circulating tumor cells (CTCs) within minutes. Using this biomimetic engineering strategy, click bubbles achieve a capture efficiency of up to 98%, improved by 20% at 15 times faster over their monovalent counterparts. Further, the buoyancy-activated bubble facilitates self-separation, 3D suspension culture, and in situ phenotyping of the captured single cancer cells. By using a multiantibody design, this fast, affordable micromotor-like click bubble enables suspended enrichment of CTCs in a cohort (n = 42) across three cancer types and treatment response evaluation, signifying its great potential to enable single-cell analysis and 3D organoid culture.

Case Report: The effective treatment of patients in advanced no-small cell lung cancer patients with EGFR G719X/S768I/L861Q and acquired MET amplification: A case series and literature review.

Preclinical cases suggest that EGFR tyrosine kinase inhibitors (TKIs) plus MET TKIs are a potential therapy for non-classical EGFR mutant lung cancers with MET amplification acquired resistance. Herein, we report for the first time the effectiveness of novel combination treatment regimens for patients with EGFR G719X/S768I/L861Q. Until the last follow-up assessment, two patients demonstrated improved survival after they switched to afatinib combined with savolitinib (PFS: 10 months) and furmonertinib combined with crizotinib (PFS: 6 months), respectively, that did not observed increased incidence and severity of adverse events. According to the findings of this study and literature review, various responses were observed from the combined therapy in NSCLC patients who harbored uncommon EGFR mutations and MET amplification. Furthermore, Next generation sequencing (NGS) leads to the discovery of uncommon of EGFR and reveals the co-mutations in NSCLC.

PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study.

Background: The aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer. Methods: In this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1/PD-L1 inhibitors plus chemotherapy group (PC group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents' group (PA group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Cox's proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis. Results: The average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression: HR 0.4, P=0.005. Death: HR 0.4, P=0.024) and PAC group (Disease progression: HR 0.3, P=0.012. Death: HR 0.3, P=0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS:7.5 vs.3.5, P=0.00052. mOS:33.1 vs.21.8, P=0.093) and PAC group (mPFS:5.1 vs.3.5, P=0.075. mOS:37.3 vs.21.8, P=0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR:96.3% vs.58.3%, P=0.001) and PAC group (DCR:100% vs.58.3%, P=0.019) had a better disease control rate (DCR) than patients in PC group. Conclusion: PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.

The Effect of PD-1 Inhibitor Combined with Chemotherapy on the Level of Peripheral Blood T Lymphocytes among Patients with Non-Small-Cell Lung Cancer and Its Relationship with Prognosis.

Objective: To explore the effect of combined treatment of PD-1 inhibitor and chemotherapy on the level of peripheral blood T lymphocytes in non-small-cell lung cancer (NSCLC) patients and its relationship with prognosis. Methods: Retrospective analysis was conducted on 150 NSCLC patients treated in Guangxi Medical University Affiliated Tumor Hospital from June 2018 to September 2020, including 77 patients treated with PD-1 inhibitor combined with chemotherapy as the observation group (OG) and 73 patients with chemotherapy alone as the control group (CG). Therapeutic efficacy, immune function indexes, serum tumor markers, incidence of adverse reactions during hospitalization, 1-year survival rate, and life quality after 6 months of treatment were observed and compared between two groups. Results: Compared to the CG, the therapeutic effect of OG was evidently better. Six months after treatment, levels of CD4+/CD8+, NK cells, and CD4 + in two groups were elevated markedly, and indexes of OG were notably and comparatively higher than those in the other group. After treatment, OG was observed with a marked decline regarding levels of CYFRA21-1, CEA, and CA125 compared to those in the CG; and there was no notable difference in terms of adverse reaction occurrence between two groups, but the 1-year survival rate and 6-month life quality in OG over ranked those in CG. Conclusion: For NSCLC patients, the PD-1 inhibitor given on the basis of chemotherapy can further improve the clinical efficacy and improve immune function and long-term survival rate of patients on the premise of ensuring the safety of treatment, which is worth promoting in clinical practice.

Pretreatment Fibrinogen-Albumin Ratio (FAR) Associated with Treatment Response and Survival in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Anti-PD-1 Therapy Plus Platinum-Based Combination Chemotherapy.

PURPOSE: PD-1 inhibitors have been routinely used to treat advanced non-small cell lung cancer (NSCLC) and have significantly improved clinical outcomes. In this study, we aimed to explore the influence of pretreatment fibrinogen-albumin ratio (FAR) on treatment response and survival in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. PATIENTS AND METHODS: A total of 91 patients with advanced NSCLC were included in the study. All patients received at least two cycles of systemic first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Receiver operating characteristics analysis was performed to determine the optimal cutoff values of FAR. Univariate and multivariate analyses were used to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate survival curves. RESULTS: Multivariate logistic regression analysis showed that N stage (N2-3) and high FAR (≥0.175, optimal cutoff value) were independent predictors for objective response rate (P = 0.0002, P = 0.0005, respectively). Multivariate Cox regression analysis of progression-free survival and overall survival showed that high FAR (≥0.145) was independent prognostic factors (P = 0.0061, P = 0.0024, respectively). Progression-free survival and overall survival were significantly shorter in the high FAR (≥0.145) group than those in the low FAR (<0.145) group (P = 0.0024, P = 0.0024, respectively). CONCLUSION: Pretreatment FAR was an independent predictor for treatment response and independent prognostic factors in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.

The Association between Pretreatment anemia and Overall Survival in Advanced Non-small Cell lung Cancer: A Retrospective Cohort Study Using Propensity Score Matching.

Background: The purpose of this study was to investigate whether pretreatment anemia was an independent risk factor for survival in patients with advanced non-small cell lung cancer (NSCLC) after adjusting for other covariates. Methods: We used propensity score matching (PSM) to minimize the influence of confounding factors and used χ2 (categorical variables), Student's t-test (normal distribution), or Mann-Whitney U test (skewed distribution) to analyze the differences among the Hb groups. Cox regression and Kaplan-Meier analyses were used to assess the association between anemia and survival. P values < 0.05 (two-sided) were considered statistically significant. Results: The average age of the 758 selected participants was 58.2±11 years, and 210 patients (27.7%) had anemia. In the multivariate analysis, anemia was associated with a poor prognosis in the unmatched cohort (Hazards ratio (HR)=1.3, 95% (confidence interval (CI): 1.1-1.6; p= 0.008), and the matched cohort (HR=1.7, 95% CI: 1.3-2.3; p <0.001), emerging as an independent risk and prognostic factor in advanced NSCLC patients. In the Kaplan-Meier curve, the average survival time of anemic and non-anemic patients was 9.3 months (95% CI: 7.9-11.4 months) vs. 14.1 months (95% CI: 12-16.3 months) (p=0.0073) in the unmatched cohort. After propensity score matching, the average survival time of anemic and non-anemic patients was 10.9 months (95% CI: 8.8-12.9. months) vs. 17.8 months (95% CI: 16.0-23.3 months) (p <0.001). Conclusion: Pretreatment anemia was an independent risk and prognostic factor for survival in patients with advanced NSCLC. Large-scale studies are required to confirm our findings.

Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC). METHODS: Twenty-three randomized clinical trials and seven real-world studies were included in this meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) and odds ratios for the overall response rate (ORR) were extracted. A fixed-effects or random-effects model was applied to obtain pooled estimates. RESULTS: Data from 16 high-quality trials involving 10,643 NSCLC patients receiving either immunotherapy or chemotherapy/placebo enabled direct comparison of the survival impact of smoking. Anti-PD-1/PD-L1/CTLA-4 immunotherapy was found to significantly prolong OS and PFS as compared to chemotherapy/placebo in smokers (HR for OS, 0.76 [0.69-0.83], P<0.00001; HR for PFS, 0.65 [0.56-0.75], P<0.00001), and these trends were less or not significant in non-smokers (HR for OS, 0.91 [0.78-1.06], P=0.25; HR for PFS, 0.68 [0.45-1.03], P=0.07). Consistent results were obtained for the first-line or second/third-line use of immunotherapy and for non-squamous NSCLC patients only. Furthermore, the data from 7 trials and 7 real-world studies involving 4,777 patients receiving immunotherapy allowed direct comparison of therapeutic outcomes between smokers and non-smokers. Prolonged OS (HR 0.86 [0.75-0.99], P=0.04) and PFS (HR 0.69 [0.60-0.81], P<0.0001) and a higher response rate (ORR 1.20 [0.94-1.53], P=0.15) were observed in smokers compared to non-smokers receiving immunotherapy. CONCLUSIONS: Immunotherapy was found to have a greater benefit in NSCLC patients with a smoking history than in those who had never smoked.

Comparison of Different EGFR Gene Mutation Status in Patients with Metastatic Non-Small Lung Cancer After First-Line EGFR-TKIs Therapy and Analyzing Its Relationship with Efficacy and Prognosis.

PURPOSE: The purpose of this study is to compare the different EGFR mutation status in patients with metastatic non-small cell lung cancer (NSCLC) after first-line EGFR-TKIs therapy and analyze its relationship with efficacy and prognosis. PATIENTS AND METHODS: This study retrospectively analyzed the data of patients with metastatic NSCLC harboring EGFR mutation in the Affiliated Tumor Hospital of Guangxi Medical University from June 2016 to December 2020. Samples were collected before treatment and at the time of disease progression after first-line EGFR-TKIs therapy. Amplification refractory mutation system (ARMS) PCR and next-generation sequencing (NGS) were used to detect EGFR mutation. ORR, DCR, and PFS of different EGFR mutation groups were compared. RESULTS: The EGFR mutation rate of re-biopsy was 60.23%. The inconsistency rate of EGFR mutations in the same and different simple types was 72.22% (26/36) and 92.31% (48/52), respectively. Alterations in terms of EGFR mutations were divided into four groups: Group A: EGFR-sensitive mutation negative and T790M negative (39.77%); Group B: EGFR-sensitive mutation positive and T790M negative (18.19%); Group C: EGFR-sensitive mutation negative and T790M positive (36.36%); Group D: EGFR-sensitive mutation positive and T790M positive (5.68%). The differences between the four groups in ORR and DCR were not statistically significant (P>0.05). The median PFS of all patients was 10.65 months. PFS of Group A, B, C, and D was 12.26, 7.96, 10.55, and 13.81 months, respectively, with statistical significance (Log rank P = 0.014). CONCLUSION: EGFR mutation status in metastatic NSCLC patients receiving the first- and second-generation TKIs after disease progression show diversity. Monitoring the EGFR mutation changes is of great importance for subsequent clinical decision-making and exploring the underlying mechanisms of acquired resistance.

Vision therapy for intermittent exotropia: A case series

Introduction: We evaluated the effectiveness of office-based vergence/accommodative therapy with home reinforcement for intermittent exotropia in a private practice environment. Methods: This was a retrospective chart review study. Patients who received office-based vision therapy for intermittent exotropia in a private optometric clinic were reviewed. Patients with intermittent exotropia treated with and without strabismus surgery were both included. The pre-therapy baseline data were compared to the re-evaluation data obtained at the last therapy session. All patients received office-based vergence/accommodative therapy administered by a trained therapist during a 60 min office visit every one to two weeks, combined with home reinforcement for a minimum of 15 min, five times per week. The primary outcome measure in this study was the change in the Office Control Score from the pre-therapy visit to the post-therapy visit. The hypothesis was that office-based vergence/accommodative therapy would significantly improve the Office Control Score. Results: Forty patients aged from 5 to 22 years old fulfilled the inclusion criteria. Eight of them were postoperative patients. After treatment, there was a change of −1.1 ± 1.6 (p < 0.001, z = 3.73, effect size: 0.42) and −1.1 ± 1.4 (p < 0.001, z = 4.26, effect size: 0.48) in distance and near Office Control Score, respectively. In the subgroup analysis, significant improvements in the Office Control Score were observed in both the operated and unoperated intermittent exotropes at distance and near. Conclusion: This study showed that office-based vergence/accommodative therapy with home reinforcement significantly improved the distance and near control of exodeviation in both operated and unoperated intermittent exotropia patients in a private practice environment. (AU)

Practices and Hindrances in Cancer Pain Management: Results of a National Multi-Cancer Center Survey Among Healthcare Professionals in China.

BACKGROUND: Inadequate control of cancer-related pain in China is an ongoing problem. This study investigated the practices of cancer pain (CP) management at major cancer centers in China and perceived hindrances and knowledge of CP management among health professionals. METHODS: From September to October 2019, a survey was conducted using electronic questionnaires via the internet to investigate the practices, and perceived hindrances and knowledge in managing CP among healthcare professionals from 7 provincial cancer centers in China. The questionnaire included demographic data, the professionals' practices among their own patients, their opinions regarding hindrances to CP management, and knowledge of CP management. RESULTS: We gathered validated responses from 411 anonymous healthcare professionals, with 82.2% (411/500) of response rate. Based on the analysis of these 411 questionnaires, the results demonstrated that CP was prevalent among patients with cancer, while moderate-to-severe pain took a great proportion. CP management was inadequate for a significant proportion of the patients with CP. Pain assessment, analgesic treatment, attention to adverse effects of analgesic, and multidisciplinary management were usually ineffectual in many cases. The duration of work experience did not significantly affect CP management. The respondents considered that both patients and healthcare professionals were responsible for the undermanagement of CP. Only 26 (6.3%) respondents were able to answer correctly all 10 of the professional questions regarding CP. CONCLUSION: CP is commonly undermanaged in China. Effective pain control requires the implementation of standards, and the sufficient attention and training of healthcare professionals.

Vision therapy for intermittent exotropia: A case series.

INTRODUCTION: We evaluated the effectiveness of office-based vergence/accommodative therapy with home reinforcement for intermittent exotropia in a private practice environment. METHODS: This was a retrospective chart review study. Patients who received office-based vision therapy for intermittent exotropia in a private optometric clinic were reviewed. Patients with intermittent exotropia treated with and without strabismus surgery were both included. The pre-therapy baseline data were compared to the re-evaluation data obtained at the last therapy session. All patients received office-based vergence/accommodative therapy administered by a trained therapist during a 60 min office visit every one to two weeks, combined with home reinforcement for a minimum of 15 min, five times per week. The primary outcome measure in this study was the change in the Office Control Score from the pre-therapy visit to the post-therapy visit. The hypothesis was that office-based vergence/accommodative therapy would significantly improve the Office Control Score. RESULTS: Forty patients aged from 5 to 22 years old fulfilled the inclusion criteria. Eight of them were postoperative patients. After treatment, there was a change of -1.1 ±â€¯1.6 (p < 0.001, z = 3.73, effect size: 0.42) and -1.1 ±â€¯1.4 (p < 0.001, z = 4.26, effect size: 0.48) in distance and near Office Control Score, respectively. In the subgroup analysis, significant improvements in the Office Control Score were observed in both the operated and unoperated intermittent exotropes at distance and near. CONCLUSION: This study showed that office-based vergence/accommodative therapy with home reinforcement significantly improved the distance and near control of exodeviation in both operated and unoperated intermittent exotropia patients in a private practice environment.

STRN-ALK Fusion in Lung Adenocarcinoma with Excellent Response Upon Alectinib Treatment: A Case Report and Literature Review.

Non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) rearrangement benefit from treatment with ALK inhibitors. Therefore, the identification of druggable ALK fusions is necessary for NSCLC treatment. More than 90 fusion partners of ALK have been reported in NSCLC patients, but the striatin gene (STRN)-ALK fusion has rarely been reported. Moreover, the response of STRN-ALK fusion patients treated with ALK inhibitors remains to be explored. A 64-year-old Chinese male with no history of smoking or alcohol consumption was diagnosed as stage IVB lung adenocarcinoma (LADC) (cT4N3M1c) in October 2018. Next-generation sequencing (NGS) targeting 425 cancer-related genes was performed on the plasma and supernatant of pleural effusion samples and revealed an STRN-ALK fusion. The patient received alectinib (600 mg, twice daily) as the first-line treatment with an excellent response exceeding 19 months. This is the first report of a NSCLC patient harboring an STRN-ALK fusion and exhibiting an excellent response to alectinib treatment. This case provides valuable information for therapeutic decision-making of patients with STRN-ALK fusions. Furthermore, this case also highlighted the advantage of performing targeted NGS on circulating tumor DNA for the identification and analysis of rare, druggable genomic alterations.

Predictive value of tumor genetic alteration profiling for chemotherapy and EGFR-TKI treatment in advanced NSCLC.

Previous studies have suggested that a variety of tumor driver genetic alterations affected the treatment efficacy of chemotherapy and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). The present study aimed to investigate the association between the tumor genetic alteration landscape and the treatment outcome of first-line chemotherapy and EGFR-TKIs in advanced NSCLC. A total of 94 patients with advanced NSCLC were recruited. All patients received first-line chemotherapy and/or EGFR-TKIs (either first- or second-generation EGFR-TKI, or third-generation EGFR-TKI) alone or sequentially. Prior to chemotherapy and/or EGFR-TKI treatment, plasma, effusion and/or tumor tissues from the included patients were subjected to next-generation sequencing, targeting 59 genes. The results indicated that the positive genetic alteration status prior to first-line chemotherapy was associated with prolonged progression-free survival (PFS) time compared with the negative status [9.1 vs. 4.0 months; hazard ratio (HR)=6.68; 95% CI, 2.25-19.82; P=0.001). Furthermore, patients with EGFR activating mutation harboring concomitant alterations exhibited a shorter PFS (11.1 vs. 7.4 months; HR=2.14; 95% CI, 1.03-4.44; P=0.04) and overall survival (OS) time [not reached (NR) vs. 32.8 months; HR=4.30; 95% CI, 1.41-13.16; P=0.01] than those without concomitant alterations, with first- and second-generation EGFR-TKI treatment. Similarly, patients with T79M mutation harboring concomitant alterations exhibited a shorter PFS (15.6 vs. 3.6 months; HR=9.48; 95% CI, 2.29-39.28; P=0.002) and OS time (NR vs. 32.8 months; HR=4.85; 95% CI, 1.16-20.29; P=0.03) with osimertinib treatment. Taken together, the results demonstrated that positive genetic alteration status predicted greater efficacy of first-line chemotherapy, while concomitant genetic alterations were associated with poor treatment outcome for first- or second-generation EGFR-TKI and third-generation EGFR-TKI treatment.

Apatinib reverses alectinib resistance by targeting vascular endothelial growth factor receptor 2 and attenuating the oncogenic signaling pathway in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene-positive lung cancer cell lines.

Overexpression of insulin growth factor 1 receptor (IGF-1R) and its ligand, insulin growth factor 1 (IGF-1), is related to treatment resistance and worse prognosis in many types of tumors. We reported recently that IGF-1R activation by IGF induces resistance to alectinib and stimulates the production of vascular endothelial growth factor, which indicates that IGF induces alectinib resistance and angiogenesis. This study aimed to determine the effect of bigeminal inhibition of anaplastic lymphoma kinase (ALK) and angiogenesis on human insulin growth factor 1 receptor (hIGF-1)-triggered drug resistance in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-positive lung cancer. Human lung adenocarcinoma H3122 and H2228 cells were exposed to a combination of insulin growth factor 1 receptor (IGF-1), alectinib, or apatinib. The effects of the combination therapy were examined using cell the Cell Counting Kit-8 assay, the colony-forming assay, the scratch test, and flow cytometry analysis, and the molecular mechanism was assessed by western blot. At nontoxic concentrations, apatinib restored alectinib sensitivity by increasing drug-induced apoptosis and inhibiting viability, migration, and invasion in IGF-triggered drug resistant cells. Moreover, we found that apatinib restored sensitivity to alectinib mainly through suppression of the ALK downstream signaling pathway and antiangiogenesis signaling. Taken together, our results indicate that simultaneous inhibition of ALK and vascular endothelial growth factor R2 by the combination of alectinib with apatinib may be useful for controlling progression of EML4-ALK fusion gene lung cancer by reversing ALK-TKI resistance and inhibiting angiogenesis.

Wogonoside induces apoptosis in human non-small cell lung cancer A549 cells by promoting mitochondria dysfunction.

Non-small cell lung cancer (NSCLC) is one of the most prevailing malignancies worldwide. It has been previously shown that wogonoside exerts anti-tumor activities in various kinds of human cancers. But its role in NSCLC remains elusive. In the present study, we determined the anti-tumor effect of wogonoside in human NSCLC A549 cells. We found that wogonoside effectively inhibits A549 cell viability through inducing cell cycle arrest and apoptosis. Moreover, administration of wogonoside by intraperitoneal injection inhibits the growth of A549 cell xenografts in athymic nude mice. Additionally, mitochondrial membrane potential was disrupted and cytochrome c was released to cytosol in the wogonoside-treated A549 cells. Finally, we found that AMPK/mTOR signaling might be implicated in the anti-NSCLC efficacy of wogonoside. Therefore, we may assume that wogonoside may be considered as a potential therapeutic agent for the treatment of NSCLC.

Effect of Vision Therapy on Accommodation in Myopic Chinese Children.

Introduction. We evaluated the effectiveness of office-based accommodative/vergence therapy (OBAVT) with home reinforcement to improve accommodative function in myopic children with poor accommodative response. Methods. This was a prospective unmasked pilot study. 14 Chinese myopic children aged 8 to 12 years with at least 1 D of lag of accommodation were enrolled. All subjects received 12 weeks of 60-minute office-based accommodative/vergence therapy (OBAVT) with home reinforcement. Primary outcome measure was the change in monocular lag of accommodation from baseline visit to 12-week visit measured by Shinnipon open-field autorefractor. Secondary outcome measures were the changes in accommodative amplitude and monocular accommodative facility. Results. All participants completed the study. The lag of accommodation at baseline visit was 1.29 ± 0.21 D and it was reduced to 0.84 ± 0.19 D at 12-week visit. This difference (-0.46 ± 0.22 D; 95% confidence interval: -0.33 to -0.58 D) is statistically significant (p < 0.0001). OBAVT also increased the amplitude and facility by 3.66 ± 3.36 D (p = 0.0013; 95% confidence interval: 1.72 to 5.60 D) and 10.9 ± 4.8 cpm (p < 0.0001; 95% confidence interval: 8.1 to 13.6 cpm), respectively. Conclusion. Standardized 12 weeks of OBAVT with home reinforcement is able to significantly reduce monocular lag of accommodation and increase monocular accommodative amplitude and facility. A randomized clinical trial designed to investigate the effect of vision therapy on myopia progression is warranted.