Efficacy and safety of pembrolizumab as first-line treatment for advanced non-small cell lung cancer complicated with chronic obstructive pulmonary disease: protocol for a prospective, single-arm, single-center, phase II clinical trial.

Background: The first-line standard treatment option for patients with NSCLC complicated with Chronic obstructive pulmonary disease (COPD) is still unclear and relies on the treatment option of NSCLC alone. To date, a limited number of retrospective studies have explored the efficacy and safety of immunotherapy in patients with NSCLC complicated with COPD. We therefore designed this study to further explore the efficacy and safety of first-line immunotherapy in patients with NSCLC complicated with COPD. Methods: This study was designed as a single-armed, single-center, prospective, phase II clinical study. It will include 30 advanced (stage IV) NSCLC combined with COPD primary treatment subjects. Each subject's diagnosis will be confirmed by clinical, radiographic, pathologic, and pulmonary function evaluation. A fixed dose of 200 mg pembrolizumab will be administered by intravenous infusion on day1 every 3 weeks (Q3W). The management of stable and acute exacerbations of COPD include home oxygen therapy, and the use of conventional medications are also administered. Imaging evaluation will be performed every 6 weeks for 6 months from the first pembrolizumab dose and approximately every 12 weeks thereafter until disease progression or early withdrawal. COPD status will be evaluated every 3 months by pulmonary function, GOLD grading, mMRC score, CAT score, ABCD grouping, and AECOPD severity. The primary outcome is Progression-free survival. The secondary outcome measures include objective response rate, overall survival, rate of acute exacerbations of COPD (times/year), lung function, mMRC score, CAT score, impact of treatment on patient's health-related quality of life, antibiotic use (including duration and classes), and adverse events associated with immune checkpoint inhibitors. Exploratory endpoint is to explore the association between COPD grade and the degree of immune cell (CD4+ T lymphocytes and CD8+ T lymphocytes) infiltration, as well as the association between COPD grade and the efficacy of immune checkpoint inhibitors. Clinical trial registration: ClinicalTrials.gov, identifier NCT05578222.

Impact of chronic obstructive pulmonary disease on the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy for resectable non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: Neoadjuvant immune checkpoint inhibitors(ICIs) combined with chemotherapy can improve non-small cell lung cancer(NSCLC) patients' pathological responses and show promising improvements in survival. Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease, and its associated abnormal inflammatory response affects not only the immunotherapy efficacy but also immune-related adverse events. It remains unclear whether NSCLC patients with COPD can benefit from neoadjuvant ICIs combined with chemotherapy. METHODS: A retrospective observational clinical study was conducted on 105 consecutive NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy at the Department of Thoracic Surgery of Tianjin Chest Hospital between April 2020 and April 2023. RESULTS: A total of 74 NSCLC patients were included in the study, including 30 patients with COPD and 44 patients without COPD. The percentage of patients with a pathological complete response (PCR) was higher in the COPD group than in the non-COPD group (43.3% vs. 20.5%, P = 0.042). Multivariate logistic regression analysis of factors associated with PCR showed that the adjusted odds ratio (OR) was statistically significant for presence of COPD (OR = 3.020, 95%CI: 1.042-8.757; P = 0.042). Major pathological response (66.7% vs. 50%, P = 0.155), R0 resection rate (96.7% vs.93.2%, P = 0.642), N2 lymph node downstaging(92.3% vs. 66.7%, P = 0.182) and objective response rate (70% vs. 63.6%, P = 0.57) were not significantly different between the groups. Progression-free survival(PFS) was not reached in the COPD group and 17 months (95%CI: 12.1-21.9) in the non-COPD group, with statistically significance (χ2 = 6.247, P = 0.012). Multivariate Cox's regression analysis showed that the adjusted hazard ratio (HRadj) was statistically significant for presence of COPD (HRadj = 0.321, 95%CI: 0.111-0.930; P = 0.036). The grade 3 and grade 4 adverse events in the COPD group were leukopenia (3.3%, 6.7%), neutropenia (3.3%, 6.7%), fatigue (6.7%, 0%), gastrointestinal reactions (3.3%, 0%), and hypothyroidism (3.3%, 0%). In the non-COPD group, the corresponding adverse events were leukopenia (6.8%, 6.8%), neutropenia (3.3%, 6.8%), fatigue (2.3%, 0%), gastrointestinal reactions (2.3%, 0%), and hypothyroidism (2.3%, 0%), respectively. CONCLUSIONS: The present study indicates that the presence of COPD may improve PCR, prolong PFS, and have an acceptable safety profile in NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy.

Influence of Tumor Cavitation on Assessing the Clinical Benefit of Anti-PD1 or PD-L1 Inhibitors in Advanced Lung Squamous Cell Carcinoma.

PURPOSE: A considerable portion of lung squamous cell cancer (LUSC) displays radiographic signs of cavitation. The cavitation of lesions is not accounted for in the prevailing Evaluation Criteria of Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or iRECIST in lung cancer. We hypothesized that cavitation might alter response assessment in these patients. PATIENTS AND METHODS: We performed a retrospective radiologic review of 785 patients with stage IV LUSC treated with PD-1/PD-L1 antibody combined with platinum-based doublet chemotherapy. 131 patients exhibited cavitation lesions pre- or after-treatment. Response was assessed by RECIST v1.1 and a modified Evaluation Criteria in Solid Tumors (mRECIST) guidelines in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. The response rate and PFS and OS between mRECIST and RECIST v1.1 were compared. Survival curves of different response categories in each criterion were prepared using the method of Kaplan-Meier and log-rank tests. Weighted κ statistics were used to assess interobserver reproducibilities and to compare response rates. The chi-square test confirmed the relationship between PD-L1 expression and post-treatment cavitation. RESULTS: Notable cavitation of pulmonary lesions was seen in 16.7% of 785 patients treated with immunotherapy combined with platinum-based chemotherapy. Using the mRECIST for response assessment resulted in a higher response rate than RECIST v1.1 (66% vs. 57%). mRECIST might better identify patients with PFS and OS benefits who have cavitation. The chi-square test revealed a marginally significant difference between PD-L1 expression and tumor cavitation. Interobserver reproducibility of mRECIST for tumor cavitation evaluation was acceptable (the weighted k coefficients for mRECIST criteria was 0.821). CONCLUSION: Cavitation lesions at baseline and after checkpoint treatment are common in LUSC patients. mRECIST records a significantly higher response rate than RECIST for these LUSC patients. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions. These results may inform further modifications to RECIST V1.1 to better reflect efficacy with immunotherapy.

Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study.

Background: In the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations. Methods: We enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results: After PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups. Conclusions: In real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Two case reports: EML4-ALK rearrangement large cell neuroendocrine carcinoma and literature review.

Anaplastic lymphoma kinase gene (ALK) rearrangement is present in only approximately 5% of non-small cell lung cancers (NSCLCs) and is scarce in LCNEC patients. The conventional first-line treatment options are chemotherapy combined with immunotherapy or chemotherapy followed by palliative radiotherapy. In this report, we present two cases of metastatic LCNEC with EML4-ALK fusion that were treated with ALK-TKI inhibitors and demonstrated a rapid therapeutic response. Both patients were nonsmoking women who declined cytotoxic chemotherapy, underwent Next-Generation Sequencing (NGS), and confirmed EML4-ALK fusion. They were treated with alectinib as first-line therapy, and the tumors showed significant shrinkage after two months, achieving a PR (defined as a more than 30% decrease in the sum of maximal dimensions). The PFS was 22 months and 32 months, respectively, until the last follow-up. A systematic review of all previously reported cases of LCNEC with ALK mutations identified only 21 cases. These cases were characterized by being female (71.4%), nonsmoking (85.7%), diagnosed at a relatively young age (median age 51.1), and stage IV (89.5%), with an overall response rate (ORR) of 90.5%. PFS and OS were significantly longer than those treated with conventional chemotherapy/immunotherapy. Based on the clinical characteristics and the effective therapeutic outcomes with ALK inhibitors in LCNEC patients with ALK fusion, we recommend routine ALK IHC (economical, affordable, and convenient, but with higher false positives) as a screening method in advanced LCNEC patients, particularly nonsmoking females or those who are not candidates for or unwilling to undergo cytotoxic chemotherapy. Further molecular profiling is necessary to confirm these potential beneficiaries. We suggest TKI inhibitors as the first-line treatment for metastatic LCNEC with ALK fusion. Additional studies on larger cohorts are required to assess the prevalence of ALK gene fusions and their sensitivity to various ALK inhibitors.

International expert consensus on diagnosis and treatment of lung cancer complicated by chronic obstructive pulmonary disease.

Background: Lung cancer combined by chronic obstructive pulmonary disease (LC-COPD) is a common comorbidity and their interaction with each other poses significant clinical challenges. However, there is a lack of well-established consensus on the diagnosis and treatment of LC-COPD. Methods: A panel of experts, comprising specialists in oncology, respiratory medicine, radiology, interventional medicine, and thoracic surgery, was convened. The panel was presented with a comprehensive review of the current evidence pertaining to LC-COPD. After thorough discussions, the panel reached a consensus on 17 recommendations with over 70% agreement in voting to enhance the management of LC-COPD and optimize the care of these patients. Results: The 17 statements focused on pathogenic mechanisms (n=2), general strategies (n=4), and clinical application in COPD (n=2) and lung cancer (n=9) were developed and modified. These statements provide guidance on early screening and treatment selection of LC-COPD, the interplay of lung cancer and COPD on treatment, and considerations during treatment. This consensus also emphasizes patient-centered and personalized treatment in the management of LC-COPD. Conclusions: The consensus highlights the need for concurrent treatment for both lung cancer and COPD in LC-COPD patients, while being mindful of the mutual influence of the two conditions on treatment and monitoring for adverse reactions.

Identification and Validation of a GPX4-Related Immune Prognostic Signature for Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is a commonly occurring histological subtype of lung cancer. Glutathione peroxidase 4 (GPX4) is an important regulatory factor of ferroptosis and is involved in the development of many cancers, but its prognostic significance has not been systematically described in LUAD. In this study, we focused on developing a robust GPX4-related prognostic signature (GPS) for LUAD. Data for the training cohort was extracted from The Cancer Genome Atlas, and that for the validation cohort was sourced from the GSE72094 dataset including 863 LUAD patients. GPX4-related genes were screened out by weighted gene coexpression network analysis and Spearman's correlation analysis. Then, Cox regression and least absolute shrinkage and selection operator regression analyses were employed to construct a GPS. The ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and GSEA were utilized to evaluate the relationship between GPS and the tumor microenvironment (TME). We constructed and validated a GPS premised on four GPX4-related genes (KIF14, LATS2, PRKCE, and TM6SF1), which could classify LUAD patients into low- and high-score cohorts. The high-risk cohort presented noticeably poorer overall survival (OS) as opposed to the low-risk cohort, meaning that the GPS may be utilized as an independent predictor of the OS of LUAD. The GPS was also adversely correlated with multiple tumor-infiltrating immune cells and immune-related processes and pathways in TME. Furthermore, greater sensitivity to erlotinib and lapatinib were identified in the low-risk cohort based on the GDSC database. Our findings suggest that the GPS can effectively forecast the prognosis of LUAD patients and may possibly regulate the TME of LUAD.

ZNF143 Expression is Associated with COPD and Tumor Microenvironment in Non-Small Cell Lung Cancer.

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory-related disease highly associated with increased lung cancer risk. Studies have explored the tumor promoting roles for zinc finger protein 143 (ZNF143). However, the role of ZNF143 in COPD and tumor microenvironment of non-small cell lung cancer (NSCLC) has not been fully elucidated. Methods: COPD-related key genes were identified by differential gene expression evaluation, WGCNA and SVM-RFE analysis using mRNA expression data retrieved from public databases. ROC analysis was conducted to evaluate the diagnostic value of ZNF143. Correlation between ZNF143 and clinic-pathological features, associations with tumor-infiltrating immune cells (TICs) and the relationship with predictors of immunotherapy efficacy were explored. ZNF143 gene expression was validated by qRT-PCR using an independent cohort. Results: Bioinformatic and machine learning analysis showed that ZNF143 was a COPD-related gene. ZNF143 expression was significantly upregulated in COPD and is a potential diagnostic biomarker in COPD with AUC > 0.85. ZNF143 expression was significantly upregulated in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). ZNF143 expression levels were significantly higher in LUAD patients with COPD relative to the levels in patients only with LUAD. Upregulation of ZNF143 in patients with comorbidity of NSCLC and COPD was further confirmed by qRT-PCR analysis. High expression of ZNF143 was significantly correlated with advanced TNM stage in LUSC. High ZNF143 expression was associated with activated TICs in both LUAD and LUSC samples. Moreover, ZNF143 expression was significantly correlated with the levels of several known predictors of immunotherapy efficacy, including PD-L1, PD-L2, TMB and TIDE in NSCLC. Conclusion: ZNF143 is a novel COPD biomarker. High expression level of ZNF143 is associated with immune microenvironment and high risk of progression of COPD to NSCLC.

Prognostic and Immunological Role of FAT Family Genes in Non-Small Cell Lung Cancer.

BACKGROUND: The FAT atypical cadherin 1/2/3/4 (FAT1/2/3/4) has been linked to the occurrence and development of various cancers. However, the prognostic and immunological role of FAT1/2/3/4 in non-small cell lung cancer (NSCLC) has not been clarified. METHODS: The association of FAT1/2/3/4 mutations with tumor mutation burden (TMB), tumor immunity in the microenvironment, and response to ICIs in NSCLC was investigated. Whole-exome sequencing data of lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) samples from the Cancer Genome Atlas (TCGA), and an immunotherapy data set comprising mutation and survival data of 75 NSCLC patients were analyzed. Two independent pan-cancer cohorts with large samples were used to validate the prognostic value of FAT1/2/3/4 mutations in immunotherapy. RESULTS: A high mutation rate of FAT1/2/3/4 (57.3%, 603/1052) was observed in NSCLC patients. TMB was significantly higher in samples with mutated FAT1/2/3/4 compared to samples with wildtype FAT1/2/3/4 (P < .05). FAT2 mutation was found to be an independent prognostic biomarker in LUAD. FAT1/2/3/4 were aberrantly expressed in LUAD and LUSC, and high FAT2 expression strongly correlated with high PD-L1 levels in LUAD. Moreover, LUAD patients with FAT1 mutations showed significantly high activated dendritic cells infiltration, whereas those with FAT2/3/4 mutations had high infiltration of CD8+ T-cells, M1 macrophages, activated memory CD4+ T-cells, and helper follicular T-cells. It was also observed that FAT1/2/4 mutations were significantly associated with better enhanced objective response and durable clinical benefit, whereas FAT1/2/3 mutations correlated with longer progression-free survival in ICI-treated NSCLC cohort. FAT1/4 mutations were related to better overall survival in pan-cancer patients treated with ICIs. CONCLUSIONS: FAT family genes are potential prognostic and immunological biomarkers and correlate with response to ICIs in NSCLC.

Identification of Recurrent Insertions and Deletions in Exon 18 and 19 of Human Epidermal Growth Factor Receptor 2 as Potential Drivers in Non-Small-Cell Lung Cancer and Other Cancer Types.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) belongs to the same family as epidermal growth factor receptor (EGFR) and is known as an important cancer driver gene. Insertions and deletions (indels) are frequent driver mutations in both EGFR and HER2. The most common HER2 indels are the exon 20 insertions within the kinase domain, while others are rarely reported. Our study aimed to investigate other indels of HER2 that may act as driver mutations in Chinese patients with different cancer types. METHODS: In this retrospective study, patient samples were subjected to targeted sequencing covering HER2 and other cancer-related genes. Mutation profiles of patients harboring HER2 exon 18/19 indels were described. Identified HER2 exon 18/19 indels in our study were compared with external data from COSMIC. In silico and in vitro analyses were performed on selected indels of HER2 exon 18 and 19, respectively. RESULTS: A total of 25 indels in HER2 exon 18/19, 17 of which being recurrent, were identified in 20 of 53,591 patients with lung cancer (0.037%), two of 5,888 patients with colorectal cancer (0.034%), two of 3,774 patients with breast cancer (0.053%), and one of 14 patients with urothelial carcinoma of the renal pelvis (7.1%). Most patients harboring HER2 exon 18/19 indels were absent of known driver mutations. In lung cancer, mutation profiles were comparable between patients carrying HER2 exon 18/19 indels and the two established HER2 drivers (exon 20 insertions and S310 mutations). The in silico and in vitro analyses suggested an activated state conferred by HER2 exon 18/19 indels, which could be targeted by different tyrosine kinase inhibitors. CONCLUSION: Our study revealed a class of rare but unique indels in HER2 exon 18/19, which may act as driver mutations in several cancer types.

Value and significance of brain radiation therapy during first-line EGFR-TKI treatment in lung adenocarcinoma with EGFR sensitive mutation and synchronous brain metastasis: Appropriate timing and technique.

BACKGROUND: For lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) sensitive mutation and synchronous brain metastasis (syn-BM), when and how to apply radiotherapy (RT) during first-line tyrosine kinase inhibitor (TKI) treatment remains debatable. METHODS: From a real-world multicenter database, EGFR-mutant patients with syn-BM diagnosed between 2010-2020 and treated with first-line TKIs were enrolled and divided into upfront TKI + RT and upfront TKI groups. Median intracranial progression-free survival (mIC-PFS), median overall survival (mOS), and their risk factors were estimated. RESULTS: There were 60 and 186 patients in the upfront TKI + RT group and upfront TKI group, respectively. Their mIC-PFS were 28.9 months (m) and 17.5 m (p = 0.023), and mOS were 42.7 m and 40.1 m (p = 0.51). Upfront brain RT improved mIC-PFS in patients ≤60-year-old (p = 0.035), with symptomatic BM (p = 0.002), and treated with first-generation TKIs (p = 0.012). There was no significant difference in mOS in any subgroup. Upfront brain stereotactic radiosurgery (SRS) showed a trend of better mIC-PFS and mOS. mIC-PFS was independently correlated with symptomatic BM (HR = 1.54, p = 0.030), EGFR L858R mutation (HR = 1.57, p = 0.019), and upfront brain RT (HR = 0.47, p = 0.001). mOS was independently correlated with being female (HR = 0.54, p = 0.007), ECOG 3-4 (HR = 10.47, p < 0.001), BM number>3 (HR = 2.19, p = 0.002), and third-generation TKI (HR = 0.54, p = 0.044) or antiangiogenic drugs (HR = 0.11, p = 0.005) as first/second-line therapy. CONCLUSIONS: Upfront brain RT based on first-line EGFR-TKI might improve IC-PFS but not OS in EGFR-mutant lung adenocarcinoma patients, indicating potential survival benefit from brain SRS and early application of drugs with higher intracranial activity.

The emergence of various genetic alterations mediated the Osimertinib resistance of a patient harboring heterozygous germline EGFR T790M: a case report.

Epidermal growth factor receptor (EGFR) T790M is the major mechanism mediating resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Despite the high frequency of EGFR activating mutations among East Asian lung cancer patients, germline T790M has been the subject of very little research. Questions remain as to whether germline T790M develops resistance to Osimertinib and if so, through which mechanisms. This study examined a patient harboring germline EGFR T790M who acquired resistance to Osimertinib therapy. After the failure of first-line icotinib therapy, which was administered for only 3 months, targeted next-generation sequencing of plasma samples collected at icotinib progression and the re-analysis of the baseline tissue biopsy sample revealed EGFR T790M with allelic frequencies approximating 50%. Lymphocyte genomic deoxyribonucleic acid (DNA) sequencing confirmed the germline heterozygous status of the T790M mutation. In addition to the EGFR T790M, a concurrent EGFR L858R was detected from the baseline tissue sample. Osimertinib therapy was initiated resulting in a partial response within 1 month of the commencement of the therapy. After 15.2 months of Osimertinib therapy, disease progression was evaluated due to the presence of pleural effusion. The targeted sequencing of plasma and pleural effusion samples revealed the emergence of EGFR G719A, tumor protein p53 (TP53) Q136X, and the co-amplification of Cyclin D1, fibroblast growth factor (FGF) 19, FGF3, and FGF4. This case highlights the importance of conducting next-generation sequencing-based molecular testing during both diagnostic and disease progression assessments to reveal sensitizing mutations and mutations that could mediate primary and acquired resistance to targeted therapeutics.

Multi-line treatment with tyrosine kinase inhibitors enabled in 4-year survival for patient with stage IV lung adenocarcinoma: a case report.

The tyrosine kinase inhibitors (TKIs) dramatically improve the clinical outcomes of non-small cell lung cancer (NSCLC) patients. Nevertheless, acquired resistance is practically inescapable in many patients. We recommended a case of lung adenocarcinoma patient, a 59-year-old Chinese woman, who was admitted to hospital with dyspnea after activity for no apparent reason. Computed tomography (CT) scan showed nodules in the anterior segment of the upper lobe of the right lung. This report presented the clinical characteristics, imaging findings, gene mutations, therapeutic regimen and outcome. The patient underwent two biopsies, found both EGFR 19 exon deletion and MET amplification, and EGFR T790M mutation was negative. In addition, ALK was positive according to the Ventana IHC test. She received successively treatment of different EGFR-TKIs and ALK-TKI, namely gefitinib, osimertinib and crizotinib. Although EGFR T790M mutation was negative after blood sample biopsy, but the possibility of tissue positive was not excluded, and the family members refused issue biopsy and chemotherapy, therefore osimertinib was taken as second-line therapy. Although gefitinib has the most lasting effect of 25 months before osimertinib and crizotinib, the disease progressed due to the emergence of acquired resistance. The patient acquired 4-year survival after treated with multi-line TKIs. As far as we know, this was the first reported case that advanced NSCLC patient had achieved such a long survival after multi-line TKIs treatment. Molecular detection and rebiopsy play important roles in the selection of therapeutic regimen for TKIs. The main take-away lesson is that multi-line TKIs treatment was an effective clinical approach for patients with advanced NSCLC.

miR­144­3p regulates the resistance of lung cancer to cisplatin by targeting Nrf2.

Chemotherapeutic drug resistance is correlated with treatment failure and poor prognosis among lung cancer patients. Numerous studies indicate the relevance of miRNAs in inducing certain drug resistance. In the course of the study, we unexpectedly found that miR­144­3p could regulate the cisplatin resistance of lung cancer cells via Nrf2. However, Nrf2 also could reverse activate the expression of miR­144­3p by binding to the ARE box in the miR­144­3p promoter. This may be a self­protection mechanism of the body. In addition, we also found that in other cancer cell lines, such as HepG2, miR­144­3p also had the function of regulating cisplatin resistance. These findings may provide some theoretical reference for the clinical inhibition of cisplatin resistance.

Molecular Conformation-Dependent Mechanoluminescence: Same Mechanical Stimulus but Different Emissive Color over Time.

A phenothiazine derivative of FCO-CzS with changeable mechanoluminescence is reported, which, upon continuous mechanical stimulus, shows mechanoluminescent emission from blue to white and yellow. Careful analysis of the experimental results, coupled with the well-understood photoluminescence theory, show that the molecular conformation transition of the phenothiazine group from quasi-axial to quasi-equatorial is responsible for this dynamic mechanoluminescence effect.

Pyrene-Based Blue AIEgen: Enhanced Hole Mobility and Good EL Performance in Solution-Processed OLEDs.

Organic luminogens with strong solid-state emission have attracted much attention for their widely practical applications. However, the traditional organic luminogens with planar conformations often suffer from the notorious aggregation-caused quenching (ACQ) effect in solid state for the π-π stacking. Here, a highly efficient blue emitter TPE-4Py with an aggregation-induced emission (AIE) effect is achieved by combining twisted tetraphenylethene (TPE) core and planar pyrene peripheries. When the emitter was spin-coated in non-doped OLEDs with or without a hole-transporting layer, comparable EL performance was achieved, showing the bifunctional property as both an emitter and a hole-transporting layer. Furthermore, its EL efficiency was promoted in doped OLED, even at a high doping concentration (50%), because of its novel AIE effect, with a current efficiency up to 4.9 cd/A at 484 nm.

[Advances in the Treatment of Relapsed Small Cell Lung Cancer].

Small cell lung cancer (SCLC) is a highly malignant tumor. The initial treatment of radiotherapy and chemotherapy are more sensitive, high remission rate, but susceptible to drug resistance and relapse after treatment. Although the treatment of lung cancer has undergone enormous changes in recent years, treatment for relapsed SCLC is still a difficult problem in clinical field. In view of the serious resistance of recurrent SCLC to the existing chemotherapeutic drugs, the research on recurrent SCLC around the world is focused on the clinical trial of new drug development, optimization of chemotherapy regimen and target drug development. This paper summarize and estimate studies and literature reports of chemotherapy and precision therapy for relapsed SCLC, hopefully it could help clinicians treat relapsed SCLC and give us clinical research direction for relapsed SCLC in the future.

Characteristics of elderly patients with COPD and newly diagnosed lung cancer, and factors associated with treatment decision.

OBJECTIVE: To investigate the clinical features, diagnosis, and treatment status of elderly patients with chronic obstructive pulmonary disease (COPD) complicated with lung cancer. PATIENTS AND METHODS: This was a retrospective study of 206 patients aged >60 years with COPD and newly diagnosed lung cancer at the Tianjin Chest Hospital Respiratory Centre between September 2008 and September 2013. Lung function, radiology, and clinical data were retrieved. RESULTS: Among all patients, 57% (117/206) were hospitalized due to acute COPD aggravation, 47% (96/206) had COPD grade III or IV, 95% (195/206), showed diffusion dysfunction in pulmonary function examination, 90% (185/206) had a history of smoking, and 26% (54/206) were treated with inhaled corticosteroids for COPD treatment. Ninety-eight patients suffered from squamous carcinoma, 73 from adenocarcinoma, and 35 from small-cell carcinoma. Clinical staging was I in 36 patients, II in 47 patients, III in 78 patients, and IV in 45 patients. Initial treatments were surgery in 59 patients, chemotherapy in 30 patients, and no treatment in 117 patients. Multivariate analysis showed that age (P<0.001), COPD grades (P=0.01), clinical staging (P<0.001), and pulmonary diffusion function (P=0.007) were independent factors associated with patients with COPD being given treatments for lung cancer. CONCLUSION: Younger patients with lower COPD grades, earlier lung cancer stage, and better pulmonary diffusion function are more likely to receive treatments.

[The expression and clinical significance of HIF-1α, COX-2 and E-cadherin in patients with lung adenocarcinoma].

BACKGROUND AND OBJECTIVE: The incidence of lung adenocarcinoma increases rapidly, and hypoxia-inducible factor-1α (HIF-1α), cyclooxygenase-2 (COX-2), E-cadherin play an important role in the proliferation and differentiation of cancer cell. The aim of this study is to investigate the clinical significance of the expression of HIF-1α, COX-2, E-cadherin in patients with lung adenocarcinoma and the internal relationship among them. METHODS: The expression levels of HIF-1α, COX-2 and E-cadherin were determined in 10 cases of normal lung issue and in 45 cases of issue of lung adenocarcinoma by immunohistochemical method. RESULTS: The positive expression rate of HIF-1α and COX-2 was 60% (27/45) and 40% (18/45) respectively in 45 cases of lung adenocarcinoma, was null in 10 cases of normal lung issue. The positive expression rate of E-cadherin was 48.9% (22/45) in 45 cases of lung adenocarcinoma, was 100% in 10 cases of normal lung issue. The expression of HIF-1α was positively correlated with the size of the cancer (P < 0.05), but not with age, smoking, lymphatic metastasis, differentiated degree and surgical-pathologic staging (P > 0.05). The expression of COX-2 was positively correlated with the size of the cancer, lymphatic metastasis, surgical-pathologic and expression of HIF-1α (P < 0.05), but not with age, smoking and differentiated degree (P > 0.05). The expression of E-cadherin was positively correlated with differentiated degree and lymphatic metastasis (P < 0.05), but not with age, smoking, the size of the cancer, surgical-pathologic and expression of HIF-1α (P > 0.05). CONCLUSIONS: The overexpression of HIF-1α and COX-2 and the downregulation of E-cadherin is found in lung adenocarcinoma. The overexpression of HIF-1α may induce the overexpression of COX-2, and is non-correlated with expression of E-cadherin.