Diagnostic and Predictive Values of 18F-FDG PET/CT Metabolic Parameters in EGFR-Mutated Advanced Lung Adenocarcinoma.

PURPOSE: The clinical implications of the metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in epidermal growth factor receptor (EGFR)-mutated lung cancer are not fully understood. The aim of this study was to evaluate the diagnostic and prognostic utility of the parameters in EGFR-mutated lung cancer patients. PATIENTS AND METHODS: We retrospectively enrolled 134 patients with advanced lung adenocarcinoma (72 EGFR-negative and 62 EGFR-positive). We evaluated the correlation between EGFR mutational status and the maximum standardized uptake value (SUVmax), as well as the associations between treatment outcomes in EGFR-mutated patients and various metabolic parameters of primary tumors. For the best predictive parameters, we calculated the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) using two SUV cutoffs: 1.5 (MTV1.5, TLG1.5) and 2.5 (MTV2.5, TLG2.5). RESULTS: Mean SUVmax was lower for EGFR-mutated tumors compared with EGFR wild-type (6.11 vs 10.41, p < 0.001) tumors. Low SUVmax was significantly associated with positive EGFR mutation (odds ratio = 1.74). Multivariate analysis for survival demonstrated that high MTV1.5, TLG1.5, MTV2.5, and TLG2.5 were independently associated with shorter progression-free survival (PFS) and overall survival (OS), and the highest hazard ratios were found in TLG1.5 (3.26 for PFS and 4.62 for OS). CONCLUSION: SUVmax may be predictive for EGFR mutational status, and MTV and TLG of primary tumors may be promising prognostic parameters; 18F-FDG PET/CT has potential utility for the risk stratification of EGFR-mutated patients treated with targeted therapy.

Combination Therapy With Polydeoxyribonucleotide and Pirfenidone Alleviates Symptoms of Acute Respiratory Distress Syndrome in Human Lung Epithelial A549 Cells.

PURPOSE: Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis. METHODS: The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-ß. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed. RESULTS: In this study, 8-µg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1ß. CONCLUSION: The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-ß-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

Impact of Pulmonary Tuberculosis on the EGFR Mutational Status and Clinical Outcome in Patients with Lung Adenocarcinoma.

PURPOSE: Although it has been suggested that pulmonary tuberculosis (TB) is associated with increased risk of lung cancer, the exact mechanism is not clearly identified. We investigated the effect of pulmonary TB on the epidermal growth factor receptor (EGFR) mutational status and clinical outcome in patients with pulmonary adenocarcinoma. MATERIALS AND METHODS: We reviewed data of patients diagnosed with pulmonary adenocarcinoma harboring EGFR mutations and treated at our institution from 2008 to 2015. We divided our population into two groups: patients with pre-existing TB lesions on chest computed tomography scan (TB group) and those without the lesions (non-TB group). We compared the differences in EGFR mutational status, response to tyrosine kinase inhibitors (TKIs) and survival between the two groups. RESULTS: A total of 477 patients with pulmonary adenocarcinoma were analyzed. One hundred eighty-three patients (39%) had EGFR-mutated tumors and 100 (21%) patients had pre-existing TB lesions. The frequency of EGFR mutation was significantly higher in the TB group compared with the non-TB group (56% vs. 34%, p=0.038). Pre-existing TB lesions were independently associated with more frequent EGFR mutations in multivariate analysis (odds ratio, 1.43). In addition, both the progression-free survival (9.1 months vs. 11.6 months, p=0.020) and the overall survival (19.4 months vs. 24.5 months, p=0.014) after first-line EGFR-TKIs were significantly shorter in the TB group than in the non-TB group. CONCLUSION: Previous pulmonary TB may be associated with more frequent EGFR mutations and poorer treatment response to EGFR-TKIs in patients with pulmonary adenocarcinoma.

Pemetrexed Continuation Maintenance versus Conventional Platinum-Based Doublet Chemotherapy in EGFR-Negative Lung Adenocarcinoma: Retrospective Analysis.

BACKGROUND: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor (EGFR)-negative lung adenocarcinoma. METHODS: A total of 114 patients with EGFR-negative lung adenocarcinoma who were treated with platinum doublet were retrospectively enrolled. We compared the survival rates between patients received pemetrexed maintenance after four-cycled pemetrexed/cisplatin and those received at least four-cycled platinum doublet without maintenance chemotherapy as a first-line treatment. RESULTS: Forty-one patients received pemetrexed maintenance and 73 received conventional platinum doublet. Median progression-free survival (PFS), which was defined as the time from the day of response evaluation after four cycles of chemotherapy to disease progression or death, was significantly higher in the pemetrexed maintenance group compared to conventional group (5.8 months vs. 2.2 months, p<0.001). Median overall survival showed an increasing trend in the pemetrexed maintenance group (22.3 months vs. 16.1 months, p=0.098). Multivariate analyses showed that pemetrexed maintenance chemotherapy was associated with better PFS (hazard ratio, 0.73; 95% confidence interval, 0.15-0.87). CONCLUSION: Compared to conventional platinum-based chemotherapy, premetrexed continuation maintenance treatment is associated with better clinical outcome for the patients with EGFR wild-type lung adenocarcinoma.

Arteriovenous fistula patency associated with angiotensin-converting enzyme I/D polymorphism and ACE inhibition or AT1 receptor blockade.

BACKGROUND: Compromise of arteriovenous fistula (AVF) patency is caused by venous intimal hyperplasia. Many studies indicated that the renin-angiotensin-aldosterone system plays an important role in the development of intimal hyperplasia. Here we determined whether angiotensin-converting enzyme (ACE) I/D polymorphism is an independent prognostic factor for AVF patency in hemodialysis (HD) patients. METHODS: One hundred and fifty-five HD patients with native AVF were enrolled and genotyped, retrospectively. The primary end point was unassisted patency of the AVF, which was defined as the time from the first fistula surgery to the AVF failure. RESULTS: The unassisted AVF patency at 58 months was 47.0% in the DD genotype group and 71.8/82.9% in ID/II groups (p < 0.01). ACE inhibitors (ACEI) or angiotensin II receptor blockers (ARB) intake had significant impact on AVF patency in the ACE DD group (p = 0.03). Using a Cox-adjusted model, we observed a significant correlation between the increase in the incidence of AVF failure and diabetic nephropathy, higher mean serum phosphorus level, and the ACE DD genotype. CONCLUSION: The ACE I/D polymorphism was associated with the development of AVF failure, and a preventive role of ACEI or ARB intake on AVF patency in ACE DD patients was observed.