Exploration on the first-line treatment of ERBB2-altered advanced non-small cell lung cancer: A multicenter retrospective study.

BACKGROUND: Although the treatment of ERBB2-altered non-small cell lung cancer (NSCLC) has been studied for many years, there are no comprehensive studies to evaluate the benefits of various therapies as first-line treatment. Through the development of immunotherapy, more and more different combination treatments were applicated in clinical practice, therefore, we conducted a multicenter retrospective study to evaluate the efficacy of different treatments. METHODS: We enrolled patients with ERBB2-altered NSCLC who had undergone at least one-line systemic anticancer treatment to evaluate the efficacy of first-line chemotherapy alone (Chemo), anti-ERBB2 tyrosine kinase inhibitor (TKI), chemotherapy plus immunotherapy (Chemo + Immuno), chemotherapy plus anti-angiogenesis therapy (Chemo + Antiangio) and chemotherapy combined with immunotherapy and anti-angiogenesis therapy (Chemo + Immuno + Antiangio). The clinical outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), one-year and three-year survival rate. RESULTS: We enroll 36 patients harboring ERBB2 mutation and 29 with ERBB2 amplification. The overall ORR was 30.8%, DCR was 69.2% and mPFS was 5.7 months. Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (7.8 vs 3.6 months, HR: 0.24, 95 %CI: 0.09-0.64, P = 0.002; 5.9 vs 3.6 months, HR: 0.36, 95 %CI: 0.15-0.88, P = 0.019; respectively), while there was no significant difference in mPFS between Chemo + Immuno or Chemo + Antiangio and Chemo (both P > 0.05), the mPFS of the first two was longer. For ERBB2-mutant patients, the mPFS was 5.9 months, and Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (12.9 vs 2.9 months, HR: 0.15, 95 %CI: 0.03-0.68, P = 0.005; 7.1 vs 2.9 months, HR: 0.50, 95 %CI: 0.29-0.88, P = 0.009, respectively). In the same therapies, patients with ERBB2 mutation or ERBB2 amplification showed no statistical significance in PFS (both P > 0.05). CONCLUSIONS: In the first-line treatment of ERBB2-altered NSCLC, chemotherapy combined with immunotherapy or anti-angiogenesis therapy may have greater survival benefits than ERBB2-target therapy, but the efficacy may not be better than that of chemotherapy.

[Effect of Different Antitumor Regimens on Incidence and Severity of Corona Virus 
Disease 2019 Pneumonia in Lung Cancer Patients: 
A Single-center Retrospective Study].

BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS: Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.

Ultrasound-Guided Dynamic Needle-Tip Positioning Method Is Superior to Conventional Palpation and Ultrasound Method in Arterial Catheterization.

Background: Dynamic needle-tip positioning (DNTP) was shown to improve arterial cannulation efficiency with fewer complications than conventional palpation and ultrasound methods by some studies. However, this is still controversial, and we performed this meta-analysis to comprehensively assess its value in arterial cannulation. Methods: A literature search of randomized controlled trials was conducted, and 11 studies were finally included. Efficiency outcomes (first-attempt success, overall success, and total cannulation time) and complications (hematoma, thrombosis, posterior wall puncture, and vasospasm) were separately analyzed. Subgroup analyses in different populations under cannulation were also performed. Results: DNTP was associated with increased first-attempt success (pooled RR = 1.792, p < 0.001), overall success (pooled RR = 1.368, p = 0.001), and decreased cannulation time (pooled SMD = −1.758, p = 0.001) than palpation. DNTP gained even more advantage in small children and infants. No significant difference in these outcomes between DNTP and conventional ultrasound method was detected. Fewer hematoma occurred in DNTP than palpation (pooled RR = 0.265, p < 0.001) or traditional ultrasound (pooled RR = 0.348, p < 0.001). DNPT was also associated with fewer posterior wall punctures (pooled RR = 0.495, p = 0.001) and vasospasm (pooled RR = 0.267, p = 0.007) than traditional ultrasound. Conclusions: DNTP was a better choice in artery cannulation than conventional palpation and ultrasound method, especially in small children and infants.

Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer.

Currently, in clinical settings, all TP53 mutations have been considered equally. However, numerous studies have demonstrated that the position and type of mutation have differential effects on prognosis. Such discrepancy can be partially due to the lack of unifying classification system for TP53 mutations. In the present study, two of the most frequently used systems were compared, according to the location of the mutation or its functional effects on p53 protein and the impact of TP53 mutations on the overall survival (OS) time of 379 Chinese patients with advanced lung cancer was analyzed. Capture-based ultra-deep targeted sequencing on plasma samples of 379 patients with advanced lung cancer was performed. The present results suggested that mutations occurring in exon 8 may be associated with shorter OS in tyrosine kinase inhibitor-naïve patients (P=0.013) and in patients previously treated with one line of treatment (P=0.032). The results of the present study provided solid evidence that not all TP53 mutations were associated with a similar prognosis. Mutations in exon 8 were found in a subgroup of patients with unfavorable prognosis across various treatment histories. To the best of our knowledge, the present study is the first to compare different TP53 mutation classification systems in a large cohort of patients with advanced lung cancer.

Diagnosis status and pathological diagnosis derived treatment of elderly lung cancer patients over 75 years old.

BACKGROUND: The number of lung cancer in the elderly is increasing. However, a disturbing number of elderly patients failed to get pathological diagnosis and therapeutic outcomes are worse than the young. This study is conducted to explore the diagnosis and treatment status of lung cancer in patients over 75 years old. METHODS: Patients diagnosed with lung cancer between September 1, 2010 and October 30, 2017 were continuously screened. The pathological diagnosis must be based on the cytology or histology diagnosis. The clinical diagnosis must be built on both typical imaging features and increased tumor markers. Clinical features and survival information were obtained and analyzed. RESULTS: A total of 338 primary lung cancer inpatients were finally included with an age of 78.02±2.94 years. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease (COPD) and cardiovascular disease; 290 of all these patients were pathologically diagnosed while the other 48 patients only got a clinical diagnosis. Among the pathological diagnosis, adenocarcinoma, squamous carcinoma and small cell lung cancer counted for 91.72%. Epidermal growth factor receptor (EGFR) detection was performed in 126 patients and 41 of them were sensitive mutated. Among all included patients, 150 were treated by the best supportive treatment (BST). Anti-cancer treatment is significantly associated with better survival than BST (P<0.001). Definite sensitive mutation is associated with improved survival than undetected patients in EGFR-tyrosine kinase inhibitors (TKIs) treatment patients (P=0.039). CONCLUSIONS: Pathological diagnosis of lung cancer in elderly patients is relatively deficient. Pathologic and molecular pathological diagnosis derived anti-cancer treatment is effective in improving survival.

Predictive and prognostic value of serum periostin in advanced non-small cell lung cancer patients receiving chemotherapy.

Periostin is an extracellular matrix protein involved in tumorigenesis and metastasis. However, the role of serum periostin as a surrogate marker for treatment efficacy is still unknown. In 122 advanced non-small cell lung cancer cases, 37 patients with benign lung disease and 40 healthy controls, serum periostin was measured by enzyme-linked immunosorbent assays. The associations of serum periostin levels with the clinic-pathological parameters, chemotherapy response, and clinical outcomes of non-small cell lung cancer patients were analyzed. Serum periostin levels were significantly higher in non-small cell lung cancer patients, and it was related significantly to bone metastasis ( p = 0.021). Serum periostin of 65 non-small cell lung cancer patients were detected before and after two cycles of chemotherapy. The patients with and without periostin response had significant difference in objective response to chemotherapy ( p = 0.001). For the 122 non-small cell lung cancer patients, the median progression-free survival was 5 months. In a multivariate analysis, performance status (hazard ratio, 1.71; 95% confidence interval, 1.10-2.67), baseline periostin (hazard ratio, 1.01; 95% confidence interval, 1.00-1.01), and periostin response (hazard ratio, 0.50; 95% confidence interval, 0.29-0.86) were significantly correlated with prognosis. In conclusion, serum periostin was elevated in advanced non-small cell lung cancer patients. Baseline periostin and periostin responses appeared to be reliable surrogate markers to predict chemotherapy response and survival in patients with advanced non-small cell lung cancer.

Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5.

Metastasis of cancer cells is a key impediment to favorable outcomes of cancer treatment. Functional roles of long noncoding RNAs in several biological processes, including metastasis, have recently been discovered. In our previous work, we reported a positive correlation of increased expression of linc00673 in NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we demonstrate that ectopic expression of linc00673 promotes migration and invasion of NSCLC cells. Furthermore, our results indicate that linc00673 could silence HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the first time identified the role of lin00673 in promoting invasion and migration of NSCLC cells. Insights from this study may help to identify novel therapeutic targets for NSCLC.

The pulmonary nodule "discovered" by pneumonia: a case report.

The number of patients diagnosed with pulmonary nodules increased as more patients with high risk of lung cancer choose low-dose computed tomography (CT) scans for the screening of cancer. Clinicians might get two questions from the patients: what is the definite diagnosis of the nodule? What should we do? We have already got many guidelines trying to solve these problems. There are also several prediction models for pulmonary nodules. However, guidelines are not suitable for all types of patients, and the reality of patients is more complicated. Here we reported a 58-year-old man with a lung nodule in the right upper lobe, which was occasionally found during a period of pneumonia. We suggested two periods of follow-up, and the patient was also admitted to a clinical trial about circulating tumor cells (CTCs). He finally accepted surgical excision with a pathologic diagnosis of adenocarcinoma. This case suggests that: we might suggest CT surveillance for patients with solid nodules about 8 mm maximum diameter; three-dimensional reconstruction of CT scans could provide more information about the details of nodules; CTCs counts of peripheral blood could be considered as a potential clue for malignancy.

Recurrent "pneumonia" in left lower lobe lasting for 8 years: a case report.

Bronchioloalveolar carcinoma (BAC) is a unique lung neoplasm with variable forms, such as single nodular, multifocal and lobar pneumonic types. The pneumonic type BAC is often difficult to differentiate from pneumonia. Here we present a case of 63-year-old Chinese male, who had recurrent cough, white sputum with pneumonic lesions in left lower lobe. He suffered from lung biopsies for three times, and finally diagnosed as high differentiated adenocarcinoma 8 years later. He was treated with four cycles of pemetrexed and cisplatin, and four cycles of docetaxel and nedaplatin. However, he did not achieve disease stabilization and is still under follow up. This case suggests that, pneumonic type adenocarcinoma may radiographically and clinically resemble infectious pneumonia. Lack of fever and leukocytosis, no response to antibiotics, air bronchogram, and accompanied nodules or patches in computed tomography (CT) scans should raise suspicion about the diagnosis of pneumonia. Lung biopsy might be the only means of ruling in a diagnosis of BAC.

Efficacy and Safety of Neurokinin-1 Receptor Antagonists for Prevention of Chemotherapy-Induced Nausea and Vomiting: Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. MATERIALS AND METHODS: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. RESULTS: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, <0.001), acute phase (85.1% vs 79.6%, <0.001), and delayed phase (71.4% vs 58.2%, <0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, <0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, <0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, <0.001; occurrence of vomiting: 22.6% vs 38.9%, <0.001; usage of rescue drugs: 23.5% vs 34.1%, <0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. CONCLUSIONS: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.

The growth arrest-specific transcript 5 (GAS5): a pivotal tumor suppressor long noncoding RNA in human cancers.

Long noncoding RNAs (lncRNAs), which refer to a group of RNAs with length more than 200 nucleotides and limited protein-coding potential, play a widespread role in regulating biological processes, such as cell differentiation, proliferation, apoptosis, and migration. LncRNAs are dysregulated in multiple cancers, playing an either oncogenic or tumor-suppressive role. LncRNA GAS5 is a recently identified tumor suppressor involved in several cancers, like breast cancer, prostate cancer, lung cancer, and colorectal cancer. The low-expression pattern confers tumor cells elevated capacity of proliferation and predicts poorer prognosis. Existing studies mirror that lncRNA GAS5 promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. In this review, we will summarize the current knowledge about this vital lncRNA, from its discovery, characteristics, and biological function to molecular mechanism in various neoplasms.

Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) was recently shown to be a remarkable prognostic factor in tumors. Moreover, some studies have indicated that the combination of NLR and platelet to lymphocyte ratio (PLR) could be a better prognostic factor. As the combined prognostic value of NLR and PLR in non-small cell lung cancer (NSCLC) is not clear, we conducted this study to explore this further. METHODS: A total of 366 primary NSCLC patients with stage III or IV were finally included. The neutrophil, platelet, and lymphocyte counts were recorded before treatment was initiated. NLR and PLR were calculated and NLR > 2.68 or PLR > 119.50 was defined as elevated. Univariate and multivariate survival analyses were conducted to test their prognostic value. RESULTS: The median of NLR and PLR were 3.14 and 152.63, respectively, in all patients. It was indicated that PLR is linearly associated with NLR. PLR is associated with survival, but is not an independent prognostic factor. Removing NLR, PLR is an independent prognostic factor (overall survival [OS]: hazard ratio [HR] = 1.918, P = 0.003; progression-free survival [PFS]: HR = 1.822, P = 0.007 in condition of NLR ≤ 2.68). It was also indicated that elevated NLR is an independent prognostic factor (OS: HR = 1.778, P = 0.009; PFS: HR = 1.535, P = 0.022) in all patients. CONCLUSIONS: PLR is a useful complement of NLR, thus, advanced NSCLC patients could be divided into three prognostic groups prior to treatment: poor: NLR > 2.68; moderate: NLR ≤ 2.68 and PLR > 119.50; and good: NLR ≤ 2.68 and PLR ≤ 119.50.

A significant cathodic shift in the onset potential and enhanced photoelectrochemical water splitting using Au nanoparticles decorated WO3 nanorod array.

Au nanoparticles decorated WO3 nanorod array was prepared and applied for solar water oxidation. Scanning electron microscopy and transmission electron microscop images showed that Au distributed on the surface of WO3 nanorod array. The surface plasmon resonance effect of Au nanoparticles contributed to the enhancement of photoelectrochemical performance of Au-WO3 photoanode, such as enhanced photocurrent density of 1.17mA/cm(2) at 1.0V vs Ag/AgCl, a cathodic shift of onset of ∼0.2V and higher stability. UV-vis absorption, electrochemical impedance and Mott-Schottky measurements proved that Au-WO3 photoanode has enhanced light absorption, lower transfer resistance, increased photogenerated carriers density and higher hole injection yield. Therefore, Au-WO3 photoanode exhibited higher photoelectrochemical performance than WO3 photoanode.

Diagnostic Accuracy of CT-Guided Transthoracic Needle Biopsy for Solitary Pulmonary Nodules.

To evaluate the diagnostic accuracy of computed tomography (CT)-guided percutaneous lung biopsy for solitary pulmonary nodules. Three hundred and eleven patients (211 males and 100 females), with a mean age of 59.6 years (range, 19-87 years), who were diagnosed with solitary pulmonary nodules and underwent CT-guided percutaneous transthoracic needle biopsy between January 2008 and January 2014 were reviewed. All patients were confirmed by surgery or the clinical course. The overall diagnostic accuracy and incidence of complications were calculated, and the factors influencing these were statistically evaluated and compared. Specimens were successfully obtained from all 311 patients. A total of 217 and 94 cases were found to be malignant and benign lesions, respectively, by biopsy. Two hundred and twenty-five (72.3%) carcinomas, 78 (25.1%) benign lesions, and 8 (2.6%) inconclusive lesions were confirmed by surgery and the clinical course. The diagnostic accuracy, sensitivity, and specificity of CT-guided percutaneous transthoracic needle biopsy were 92.9%, 95.3%, and 95.7%, respectively. The incidences of pneumothorax and self-limiting bleeding were 17.7% and 11.6%, respectively. Taking account of all evidence, CT-guided percutaneous lung biopsy for solitary pulmonary nodules is an efficient, and safe diagnostic method associated with few complications.

A serum vitamin D level <25nmol/l pose high tuberculosis risk: a meta-analysis.

BACKGROUND: Low serum Vitamin D is considered to be associated with tuberculosis while the "dangerous" level was not clear. The aim of this study was to identify the association between tuberculosis and serum Vitamin D levels via synthesis of available evidence. METHODS: A search of EMBASE, Medline, ISI Web of knowledge, and Pubmed was conducted. The number of subjects of tuberculosis and no-tuberculosis groups in four Vitamin D range. Meta-analyses were performed and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: A total of 15 studies involving 1440 cases and 2558 controls were included. A significantly increased risk of tuberculosis was found in two ranges: ≤ 12.5 nmol/L: pooled OR = 4.556, 95% CI = 2.200-9.435; 13-25 nmol/L: pooled OR = 3.797, 95% CI = 1.935-7.405. No statistically significant risk of tuberculosis was found in the range of 26-50 nmol/L (pooled OR = 1.561, 95% CI =0.997-2.442). In range 51-75 nmol/L, no positive association was found (pooled OR =1.160, 95% CI = 0.708-1.900). CONCLUSIONS: This study found that a serum Vitamin D level ≤ 25 nmol/L was significantly associated with an increased risk of tuberculosis while the range of 51-75 nmol/L was not. The range 26-50nmol/L posed potential high tuberculosis risk. Future large-scale, well-designed studies are needed to verify these results.

The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma.

Long noncoding RNAs (lncRNAs) have emerged as key regulators of tumor development and progression. The lncRNA HNF1A-antisense 1 (HNF1A-AS1) is a 2455-bp transcript on chromosome 12 with a potential oncogenic role in esophageal adenocarcinoma. Nevertheless, current understanding of the involvement of HNF1A-AS1 in lung adenocarcinoma tumorigenesis remains limited. In this study, we analyzed the roles of HNF1A-AS1 in 40 lung adenocarcinoma tissues and five lung cancer cell lines. Our results showed that HNF1A-AS1 was significantly up-regulated in lung adenocarcinoma tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with TNM stage, tumor size, and lymph node metastasis. The UCSC Cancer Genomics Browser's Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup. Moreover, HNF1A-AS1 was determined to promote tumor proliferation and metastasis, both in vitro and in vivo, by regulating cyclin D1, E-cadherin, N-cadherin and ß-catenin expression. In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin. In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma.

Ratio of maximum standardized uptake value to primary tumor size is a prognostic factor in patients with advanced non-small cell lung cancer.

PURPOSE: Ratio of maximum standardized uptake value to primary tumor size (SUVmax/tumor size) was previously demonstrated to be a more important indicator of prognosis than primary tumor SUVmax alone in surgically resected non-small cell lung cancer (NSCLC). The aim of this study was to investigate whether SUVmax/tumor size was associated with response to first-line therapy and prognosis in patients with advanced NSCLC. PATIENTS AND METHODS: A retrospective review of patients who had a pretreatment (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) before receiving first-line therapy for advanced (III & IV) NSCLC was performed. Survival curves were stratified by median SUVmax and SUVmax/tumor size by the Kaplan-Meier method and statistical differences were assessed using the log-rank test. Multivariate proportional hazards (Cox) regression analyses were applied to test the SUVmax's and SUVmax/tumor size's independency of other prognostic factors for the prediction of survival. RESULTS: In total 181 patients were enrolled into the current study. Median overall survival (OS) was 15.4 months (range, 3.1-64.0 months), progression-free survival (PFS) was 5.6 months (range, 0.8-29.1 months), and post-progression survival (PPS) was 8.2 months (range, 0-51.3 months). The statistical analysis data indicated that only clinical response to first-line therapy (P=0.000, OR =6.555) was independent prognostic factors for PFS, stage (P=0.028, OR =1.673) was associated with PPS independently, and for OS, SUVmax/tumor size (P=0.050, OR =1.656) and clinical response (P=0.002, OR =2.803) were all independent prognostic factors. CONCLUSIONS: SUVmax/tumor size may be an important indicator of prognosis in patients with advanced NSCLC.

Itraconazole can inhibit malignant pleural effusion by suppressing lymphangiogenesis in mice.

BACKGROUND: The presence of malignant pleural effusion (MPE) indicates a poor prognosis in patients with non-small cell lung cancer (NSCLC). Itraconazole has been identified as a potent inhibitor of endothelial cell proliferation that suppresses angiogenesis; however, its role in the suppression of lymphangiogenesis is still unclear. The aim of this study was to investigate the efficacy of itraconazole for MPE and the mechanism of lymphangiogenesis suppression. METHODS: Lewis lung carcinoma (LLC) cells were injected into the mouse pleural cavity to establish the MPE mouse model, followed by randomization of the mice into three groups. Each mice was injected with either a high dose of itraconazole (25 mg/kg, H-ITCZ), a low dose of itraconazole (8 mg/kg, L-ITCZ), or 50 µL of hydroxypropyl-ß-cyclodextrin (130 mg/mL, H-ß-C) into the pleural cavity four times every 3 days. The MPE of the mice was collected and measured with a 1 mL syringe. The vascular endothelial growth factor-C (VEGF-C) expression level in the MPE was detected by enzyme-linked immunosorbent assay (ELISA), while the VEGF-C expression and lymphatic micro vessel density (LMVD) in the tumor tissue was observed by immunohistochemistry (IHC) staining. RESULTS: The number of pleural tumor foci, the volume of pleural effusion, the LMVD and the VEGF-C expression levels in the tumor tissue were significantly reduced in the H-ITCZ-treated group. CONCLUSIONS: Our results revealed that itraconazole may play an important role in the MPE mice by suppressing lymphangiogenesis, which demonstrated the usefulness of itraconazole in the treatment of MPE.

A 61-year-old man with cough and white sputum.

A 61-year-old man with cough and white sputum had an abnormal pulmonary mass in the left lower lobe in the computed tomography (CT) imaging. According to the lung cancer multidisciplinary team (MDT) discussion, the patient took the left lower lobe resection and lymphadenectomy and finally diagnosed as left lung adenocarcinoma with TNM stage IIIA (pT3N2M0). After four cycles of postoperative chemotherapy with pemetrexed and nedaplatin and 10-month release, a solitary pulmonary nodule (SPN) appeared in the middle lobe of right lung in CT scanning. The patient took a second operation "the right middle lobe resection" and was diagnosed as left lung adenocarcinoma at TNM stage IV (pT3N2M1a, two lungs) with neither EGFR mutation nor ALK-EML4 fusion gene. After operation, the patient took another four cycles of postoperative chemotherapy with Docetaxel and Nedaplatin. During the follow-up, another PET/CT scanning reported that several enlarged mediastinal lymph nodes, a SPN in left upper lobe and lesion in cerebellum and the brain metastasis was also proved in MRI. The patient was now diagnosed as left lung adenocarcinoma at TNM stage IV (pT3N2M1b, brain). In the third-line therapy, the patient took the stereotactic radiotherapy for metastatic mediastinal lymph nodes and took erlotinib once a day after the radiotherapy. However, the number of small lesions on lungs was increased and the brain metastasis was enlarged. The stereotactic radiotherapy for the single brain metastasis and single agent chemotherapy of abraxane were taken. The whole body examination suggested that there was progression-free after two cycles of chemo. The patient is now took five cycles of single agent chemotherapy of abraxane. The latest whole body examination showed disease was stable with no new lesions and metastasis, performance status (PS) score is 0 and the overall survival (OS) time is 34 months.