Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial.

BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. FINDINGS: 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1-10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9-2·9] vs 1·9 months [1·9-2·2]; hazard ratio [HR] 0·82 [95% CI 0·68-1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8-22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2-8·7] vs 6·8 months [5·9-7·8]; HR 0·81 [95% CI 0·69-0·95], p=0·0077), as were progression-free survival (median 2·6 months [95% CI 2·0-2·9] vs 1·9 months [1·9-2·1]; HR 0·81 [95% CI 0·69-0·96], p=0·0103) and disease control (201 [51%] of 398 patients vs 157 [40%] of 397; p=0·0020). The proportion of patients with an objective response did not differ significantly between groups (22 [6%] vs 11 [3%]; p=0·0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 [10%] vs nine [2%]), of grade 3 stomatitis with afatinib (16 [4%] vs none), and of grade 3 rash or acne with erlotinib (23 [6%] vs 41 [10%]). INTERPRETATION: The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim.

The impact of active and former smoking on the severity of obstructive sleep apnea.

PURPOSE: Although obstructive sleep apnea (OSA) syndrome is a common disorder; the connection between OSA and smoking habits is still controversial. In this study, we investigated whether active smoking and pack × years of smoking have an impact on the severity of the disease regarding the patients with OSA. METHODS: This study included 964 patients referred to the Sleep Disorders Clinic between 01.01.2007 and 01.03.2013 with an overnight polysomnographic diagnosis of OSA. The correlation between smoking habits and polysomnographic parameters has been studied in detail. RESULTS: There were 684 male (79 %) and 280 female (21 %) patients, 367 (50.6 %) of whom never smoked. Of all, 20.7 % of the smokers were current smokers (n = 150) while 28.2 % were former smokers (n = 208). Active smokers had a mean age of 49.53 (SD 10.17) while former smokers and never smokers had a mean age of 51.37 (SD 10.62), 54.2 (SD 11.56), respectively, which was statistically significant (p < 0.0001). There was a significant male predominance in smoking (p < 0.0001). In addition, male patients displayed more severe OSA than female patients. (p = 0.001). Desaturation time during sleep was found to be significantly longer in the group of former smokers in comparison to never smokers (73.84 SD 97.1-52 SD 85.8) (p = 0.005). Besides, as the apnea hypopnea index increased, the mean pack × years rose significantly (p = 0.01). Severe smokers compared to mild smokers had higher AHI, lower NREM 3, higher NREM1-2 stages (p = 0. 017, p = 0.007, p < 0.001). CONCLUSION: In this study, we found that cigarette smoking was associated with early age disease; heavy smokers had more severe OSA.

The incidence of chronic thromboembolic pulmonary hypertension secondary to acute pulmonary thromboembolism.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a curable and partially preventable complication, with a substantial incidence, leading to severe morbidity and mortality. The aim of the present study was to find out the incidence of CTEPH secondary to acute pulmonary thromboembolism (PTE) using non-invasive procedures such as ventilation/perfusion (V/Q) scintigraphy and pulmonary multidetector CT (MDCT) angiography in determining the diagnosis of CTEPH. MATERIALS AND METHODS: The study included a total of 99 patients diagnosed with initial PTE between January 2010 and December 2012. The patients who received anticoagulant therapy at least for three months underwent transthoracic echocardiography (TTE) (n= 85). Thirty one patients with a SPAP value > 30 mmHg and/or an evidence of right ventricular dysfunction in TTE underwent MDCT pulmonary angiography and V/Q scintigraphy. The patients with an evidence of residual chronic thromboembolic signs in MDCT pulmonary angiography and/or segmental perfusion defect(s) in V/Q scintigraphy underwent right heart catheterization (RHC) (n= 7). The mean PAP was measured, and a vasoreactivity test was performed. During RHC, a non-contrast medium was delivered to the pulmonary arteries for pulmonary arteriography imaging. RESULTS: Among patients diagnosed with PTE, 44 were male and 55 were female. The mean age was 60 ± 17 years. Of these patients, 63.6% had history of at least one additional disease and at least one risk factor for PTE. During diagnosis, 24 subjects were considered having massive, 61 submassive and 14 non-massive PTE. Nineteen (19.1%) patients received thrombolythic therapy. Other 80 (80.8%) patients received standard anticoagulant therapy with an INR value within the therapeutic range. In 79.8% of patients, thromboembolism was bilateral, and it was unilateral in 21.8%. After a minimum of 1 year, and maximum of 2 years follow up five subjects (5.5%) were diagnosed with CTEPH. The univariate analysis showed no association between the development of CTEPH and factors like; age, etiologic risk factors for PTE, receiving thrombolytic treatment, prevalence and type of PTE. CONCLUSION: Potentially preventabl complication of pulmonary embolism; CTEPH, had a substantial incidence during follow-up.

Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non-squamous non-small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis. MATERIALS AND METHODS: Adult current or former smokers with advanced non-squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators' choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis of the LP52 signature was conducted using a clinical Qiagen/HTG assay. The primary endpoint was overall survival (OS) in LP52+ patients. RESULTS: Overall, 595 patients received veliparib + carboplatin/paclitaxel (n = 298) or chemotherapy alone (n = 297); 13% (n = 40) in each arm were LP52+. The primary endpoint was not met; median OS was 11.2 months with veliparib + carboplatin/paclitaxel versus 9.2 months with chemotherapy alone in the LP52+ subgroup (hazard ratio [HR] 0.644, 95% confidence interval [CI]: 0.396-1.048; P = .113). In the overall population, median OS was 12.1 months in both arms (HR 0.986, 95% CI: 0.827-1.176; P = .846). No new safety signals were observed. CONCLUSION: In patients with non-squamous NSCLC, there was no significant improvement in OS with veliparib + carboplatin/paclitaxel versus chemotherapy alone, although a trend toward improved OS in the LP52+ population suggests this subgroup may benefit from veliparib. Statistical power was limited due to the small sample size.

A cross-sectional observational study to investigate daily symptom variability, effects of symptom on morning activities and therapeutic expectations of patients and physicians in COPD-SUNRISE study.

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized with limitation of airflow that is not completely reversible, progressive deterioration of airways and systemic inflammation. This study has been planned to determine daily symptom variability of patients, expectations of patient and physicians from treatment and patient profiles. A total of 514 patients with COPD from 25 centers were included in this national, multicenter, cross-sectional observational study. Data regarding demographic features, concomitant diseases, history and treatment of COPD and expectations of patients and physicians were all obtained in a single visit. Mean [standard deviation (SD)] age of the patients was 64.1 (9.5) years; age range was 41-92 years, 50% of the patients were younger than 65 years and 91% were males. Educational level of the patients was at least primary school in 80.2%; and 54.3% (30.4%) of the patients had at least one concomitant disease, particularly a cardiovascular disease. Mean (SD) duration of having COPD was 5.4 (4.6) years. The majority of patients were at moderate (43.2%) and severe (35.0%) COPD stages and one or more exacerbations per year was determined in 71%. Inhaled beta-2 agonists (84.2%), inhaled steroids (76.3%) and inhaled long-acting anti-cholinergics (70.0%) were the most commonly used medications. Dyspnea (99.0%), sputum production (92.8%) and wheezing (90.5%) were the most common symptoms, and symptom variability for dyspnea (41.1%), sputum production (61.0%) and cough (53.5%) were seen the most in the morning hours (p< 0.001). Most commonly affected morning activity was climbing up/down the stairs (point of effect: 6.7), followed by wearing socks/shoes (point of effect: 4.3) and showering/bathing (point of effect: 4.2) by COPD. Major treatment expectations of patients were greater symptomatic relief (82.3%) and greater mobility (70.0%), faster symptomatic relief (61.1%) and improvement in morning activities (59.3%); while major treatment expectations of physicians included increased quality of life (100.0%) and decreased morbidity (96.0%). Quitting smoking was the most commonly recommended (88.3%) and implemented (67.9%) non-drug protective approach aimed at decreasing the frequency of exacerbations. Consequently, our results demonstrate that COPD is not a disease of only the elderly, is an important healthcare issue that often disrupt daily living of the patients due to inadequate disease awareness leading to overlooking of the symptoms by patient and physicians, and that a patient-centered approach based on the living standards, life expectancies and preferences of patients was crucial in patient management.

Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.

PURPOSE: Squamous non-small-cell lung cancer (sqNSCLC) is genetically complex with evidence of DNA damage. This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546). PATIENTS AND METHODS: Patients age ≥ 18 years with untreated, advanced sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with veliparib 120 mg twice daily (twice a day) or placebo twice a day for up to six cycles. The primary end point was overall survival (OS) in the veliparib arm versus the control arm in current smokers, based on phase II findings. Archival tumor samples were provided for biomarker analysis using a 52-gene expression histology classifier (LP52). RESULTS: Overall, 970 patients were randomly assigned to carboplatin and paclitaxel plus either veliparib (n = 486) or placebo (n = 484); 57% were current smokers. There was no significant OS benefit with veliparib in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio [HR], 0.905; 95% CI, 0.744 to 1.101; P = .266). In the overall population, OS favored veliparib; median OS was 12.2 versus 11.2 months (HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in progression-free survival (median 5.6 months per arm). In patients with biomarker-evaluable tumor samples (n = 360), OS favored veliparib in the LP52-positive population (median 14.0 v 9.6 months; HR, 0.66; 95% CI, 0.49 to 0.89), but favored placebo in the LP52-negative population (median 11.0 v 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new safety signals were observed in the experimental arm. CONCLUSION: In current smokers with advanced sqNSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy.

[Fahr's disease accompanying to lung cancer]. / Akciger kanserine eslik eden Fahr hastaligi.

Fahr's disease occurs in relation with many metabolic disorders especially with hypoparathyroidism. Imbalance of the coordination system and dysarthria were seen at the end of the treatment in a lung cancer patient treated with radiotherapy and chemotherapy. Fahr's disease was diagnosed by diffuse symmetric calcifications at white matter and basal ganglia of cerebrum and cerebellum in cranial computed tomography. Disease was thought to be caused by hypoparathyroidism with lower calcium and parathyroid hormone levels. Possible factor that caused hipoparathyroidism and also of Fahr's disease was radiotherapy performed to a wide area because of lung cancer. This case is the first Fahr's disease that was diagnosed concurrently with lung cancer.

Nocturnal hypoxia and arterial lactate levels in sleep-related breathing disorders.

BACKGROUND: Lactate may be useful in pointing out the higher risk subgroups in sleep-related breathing disorders (SRBD) with various patterns of hypoxemia. We aimed to search whether morning and night lactate levels are related to apnea-hypopnea, hypoventilation, and hypoxemia in patients with SRBD and to compare it with patients without SRBD (No-SRBD). METHODS: Eighty patients with suspected SRBD underwent polysomnography (PSG) testing. SRBD patients had obstructive sleep apnea syndrome with or without sleep-related hypoventilation/hypoxemic conditions. Patients without SRBD were in the control group. Measurements included pulmonary function testing, PSG, analysis of arterial blood gases, and arterial lactate before and after PSG. Arterial lactate was compared with SRBD and No-SRBD patients. RESULTS: Morning lactate was significantly higher in the SRBD group than the No-SRBD group (1.65 +/- 0.48 and 1.35 +/- 0.57 mmol/L, respectively) (P = 0.003). Lactate levels at night and the change overnight in lactate levels were not significantly different between groups. After an adjustment for age, gender, and body mass index, lactate levels before PSG were related to the apnea-hypopnea index (beta: 0.004, 95% CI: 0.000-0.008) and the rate of sleep-time spent under 90% oxygen saturation (T90%). The following morning lactate level was correlated with the T90% (beta: 0.005, 95% CI: 0.000-0.010). After an adjustment for lactate levels before PSG, lactate in the morning was correlated with T90% (beta: 0.004, 95% CI: 0.000-0.008). CONCLUSION: As a marker of tissue hypoxia, arterial lactate may be used to assess the severity of SRBD.

[The therapeutic effect of normobaric oxygen in experimental peritonitis and the efficiency of rectal fever, WBC, CRP and procalcitonin in monitoring response of the therapy]. / Normobarik oksijenin deneysel peritonitin tedavisindeki yeri ve tedavinin izlenmesinde rektal ates, lökosit, CRP ve prokalsitoninin etkinligi.

BACKGROUND: It was investigated the effect of using normobaric oxygen (NO) in addition to antibiotherapy in experimental peritonitis and the changes of rectal fever (RF), WBC, CRP and procalcitonin levels were evaluated. METHODS: After the preliminary research of the normal values, rats were infected by E. coli intraperitoneally. Four groups were assigned into "no therapy", "given NO", "given antibiotic", "given antibiotic + NO" groups. RESULTS: The decline of RF and WBC levels on 3rd and 5th days was recorded in antibiotic + NO group versus the other groups. It was observed that group 4 was superior to the others. The positivity of periton cultures and the inflammation in the muscle were found to be less in antibiotic + NO group. No correlation was found between pathological and microbiological recovery and blood CRP level in all groups. But a significant decrease in blood procalcitonin level was determined in group 4 compared to the other groups. On day 3, procalcitonin and CRP levels increased with increasing WBC levels. On day 5, procalcitonin levels also decreased in groups with decreased WBC levels, but no significant correlation was found between CRP and WBC levels. CONCLUSION: It was concluded that using of NO in addition to antibiotherapy could increase the success rate of experimental intraabdominal sepsis therapy and blood procalcitonin and WBC levels could be more beneficial than CRP levels in monitoring of the severity of the sepsis.

Association of ERBB Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma: Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial.

Importance: Treatment choice for lung squamous cell carcinoma could be aided by identifying predictive biomarkers. Objective: To assess whether patient outcomes in the LUX-Lung 8 trial were associated with ERBB gene family member aberrations in tumor specimens. Design, Setting, and Participants: Ad hoc secondary analysis of the LUX-Lung 8 trial conducted at 183 centers in 23 countries from March 30, 2012, to January 30, 2014. Eligible patients had stage IIIB or IV lung squamous cell carcinoma with progressive disease after 4 or more cycles of platinum-based chemotherapy. Tumor genetic analysis (TGA) was performed using next-generation sequencing in a cohort enriched for patients with progression-free survival (PFS) of more than 2 months. Epidermal growth factor receptor (EGFR) expression levels were assessed by immunohistochemistry in a separate cohort of patients from the LUX-Lung 8 population. Associations of PFS and overall survival (OS) with ERBB gene alterations and EGFR expression levels were assessed. This analysis was conducted from February 26, 2015, to June 12, 2017. Interventions: Patients were randomized 1:1 to treatment with afatinib dimaleate (40 mg/d; n = 398) or erlotinib hydrochloride (150 mg/d; n = 397). Main Outcomes and Measures: Overall survival, PFS, pooled and individual ERBB gene mutations, ERBB copy number alterations, and EGFR expression. Results: Tumor specimens from 245 patients were eligible for next-generation sequencing (TGA subset: 132 patients treated with afatinib; 113 patients treated with erlotinib). In this population, outcomes were improved with afatinib vs erlotinib treatment (PFS: median, 3.5 vs 2.5 months; hazard ratio [HR], 0.69; 95% CI, 0.51-0.92; P = .01; OS: median, 8.4 vs 6.6 months; HR, 0.81; 95% CI, 0.62-1.05; P = .12). Of 245 patients in the TGA subset, 53 (21.6%) had tumors with 1 or more ERBB mutations. Among afatinib-treated patients, PFS (median, 4.9 vs 3.0 months; HR, 0.62; 95% CI, 0.37-1.02; P = .06) and OS (median, 10.6 vs 8.1 months; HR, 0.75; 95% CI, 0.47-1.17; P = .21) were longer among those with ERBB mutation-positive disease than among those without. The presence of HER2 mutations was associated with favorable PFS and OS following afatinib vs erlotinib treatment. There was no apparent association between copy number alteration or EGFR expression level and outcome. Conclusions and Relevance: Next-generation sequencing may help identify patients with lung squamous cell carcinoma who would derive additional benefit from treatment with afatinib. The role of ERBB mutations, particularly HER2 mutations, as predictive biomarkers for afatinib treatment in this setting warrants further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT01523587.

Sex-related differences in COPD Assessment Test scores of COPD populationswith or without significant anxiety and/or depression.

BACKGROUND/AIM: Sex-related differences have not been thoroughly explored in chronic obstructive pulmonary disease (COPD). We aimed to evaluate possible sex-related differences in COPD Assessment Test (CAT) scores of COPD patients with or without significant anxiety and/or depression. MATERIALS AND METHODS: Stable COPD patients were prospectively enrolled in the study between July 2013 and April 2014. Levels of anxiety, depression, dyspnea, and health-related quality of life parameters were assessed using specific questionnaires, including the CAT and others. Demographic and clinical data were recorded and physiological tests were performed. All the data were compared to determine any sex-related differences. RESULTS: A total of 128 COPD patients (86 men, 42 women, mean age: 60.5 ± 9.3 years) were included. The women were significantly younger and had lower pack-years of cigarette smoking, and higher biomass smoke exposure, but displayed similarly severe COPD as compared to men. Beck anxiety (13.5-11) and Beck depression (15-11) inventory results were significantly higher in women than men (P = 0.04, P = 0.01). No statistically significant difference was found between the sexes in terms of CAT score, Modified Medical Research Council score, or COPD stage parameters (P > 0.05). CONCLUSION: Female patients have higher levels of depression and anxiety scores but present the same CAT scores related to COPD severity as compared to men.

Evaluation of the VeriStrat® serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study.

OBJECTIVES: Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial. MATERIALS AND METHODS: Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Spectra were evaluated to assign a VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) classification. Overall survival (OS), progression-free survival, and other endpoints were assessed with respect to pretreatment VeriStrat status; OS was the primary efficacy variable. Outcomes with other efficacy endpoints were similar. RESULTS: Of 795 patients randomized in LUX-Lung 8, 675 were classified (VS-G: 412; VS-P: 263). In the VS-G group, OS was significantly longer with afatinib versus erlotinib (HR 0.79 [95% CI: 0.63-0.98]). In the VS-P group, there was no significant difference in OS between afatinib and erlotinib (HR 0.90 [0.70-1.16]). However, there was no interaction between VeriStrat classification and treatment group for OS (pinteraction=0.5303). OS was significantly longer in VS-G versus VS-P patients, both in the overall VeriStrat-classified population (HR 0.41 [0.35-0.49]) and afatinib-treated patients (HR 0.40 [0.31-0.51]). Multivariate analysis showed that VeriStrat was an independent predictor of OS in afatinib-treated patients, regardless of ECOG PS or best response to first-line chemotherapy. CONCLUSION: VS-G classification is strongly associated with favorable survival outcomes with either afatinib or erlotinib compared with VS-P classification. In VS-G patients, survival outcomes with afatinib are superior to those with erlotinib. VeriStrat classification may guide treatment decisions in patients with SCC of the lung. ClinicalTrials.gov registration number: NCT01523587.

A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS).

OBJECTIVES: Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150). MATERIALS AND METHODS: Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity. PRIMARY ENDPOINT: progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety. RESULTS: A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR]=1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P=0.671). Median OS was 6.8 months in both arms (unstratified HR=1.03, 95% CI: 0.80-1.32; unstratified log-rank P=0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced ≥1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade ≥3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy. CONCLUSIONS: Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers.

Effectiveness of transbronchial needle aspiration in the diagnosis of exophytic endobronchial lesions and submucosal/peribronchial diseases of the lung.

The role of transbronchial needle aspiration (TBNA) in diagnosing endobronchial lung cancers has not been elucidated. The definitive combination of procedures that offers the best diagnostic yield following fiberoptic bronchoscopy remains controversial. This study was designed to investigate the diagnostic yield of transbronchial needle aspiration and other cytologic and histologic diagnostic procedures (i.e., forceps biopsy, brushing, and washing) and to assess the optimal combination for diagnosing endobronchial lung cancers. This prospective study included 95 patients presenting with visible tumors detected during bronchoscopic procedure as either an exophytic endobronchial lesion (EEL) or submucosal-peribronchial disease (SPD). Transbronchial needle aspiration, forceps biopsy, brushing, and washing were performed in all patients, and 91 patients were diagnosed. Rates of positive results were 75.8% for needle aspiration, 71.6% for forceps biopsy, 61.1% for brushing, and 32.6% for washing. Needle aspiration was used as the sole diagnostic method in 11, forceps biopsy was the sole diagnostic method in 5, and brushing was the sole diagnostic method in 4 patients. Washing was not used as the sole diagnostic method in any case. Forceps biopsy yielded the highest diagnostic rate for an EEL (86.4%); however, when compared with needle aspiration (77.9%), no significant difference was observed between these two procedures (P = 0.302). In patients with a diagnosis of SPD, needle aspiration was determined to be the sole diagnostic method in eight patients. In this group of patients, the highest rate of diagnosis was achieved with needle aspiration (72.2%), and when compared with forceps biopsy (47.2%), a significant difference between the two procedures (forceps biopsy versus needle aspiration) was observed (P = 0.049). By adding transbronchial needle aspiration to the conventional diagnostic methods (forceps biopsy, brushing, and washing), the rate of diagnosis increased from 82.1% to 95.8% (P = 0.001), and in patients with a diagnosis of SPD, this rate increased from 69.4% to 94.4% (P = 0.008). In patients with a diagnosis of an EEL, addition of needle aspiration led to an increase in diagnostic yield but this difference was not statistically significant (89.8% versus 96.6%, P = 0.250). In endobronchial lung cancers, transbronchial needle aspiration is a safe method that can be used together with conventional diagnostic procedures to increase the diagnostic yield and should be considered a valuable diagnostic tool, particularly in cases of SPD. The highest rate of diagnostic yield in this study was obtained using a combination of forceps biopsy, transbronchial needle aspiration, and brushing; washing did not contribute to this high rate.

Should Patients With COPD Be Vaccinated?

BACKGROUND: Exacerbations of COPD are a major component of the socioeconomic burden related to COPD, and frequent exacerbations are associated with greater decline in health status. Tracheobronchial infections are involved in 50-70% of exacerbations, so influenza and pneumococcal vaccines are recommended for prevention. The aim of this study was to determine the level of knowledge among COPD patients about the vaccines, find the rate of patients inoculated with both influenza and pneumococcal vaccines, and assess the effectiveness of vaccination status. METHODS: Patients with COPD were recruited from the out-patient clinic of our hospital between September and October 2012. Subject demographic data such as age, gender, level of education, and smoking status were recorded. Vaccination status, number of subjects who were informed by a health-care professional about immunization, and COPD-related emergency or hospital admissions triggered by tracheobronchial infections over 1 y after administration of both influenza and pneumococcal vaccines were noted. RESULTS: Eighty-eight subjects were enrolled during the study period. Eighty-two subjects were male (93.2%), 6 subjects were female (6.8%), and the median age was 61.5 y. According to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006 classification, 5 subjects were in stage 1 (5.7%), 22 subjects were in stage 2 (25%), 34 subjects were in stage 3 (38.6%), and 27 subjects were in stage 4 (30.7%). Sixty-two subjects had graduated from primary school (70.5%), 21 subjects had graduated from high school (23.9%), one subject had graduated from university (1.1%), and 4 subjects had no education (4.5%). Forty-five subjects (51%) were vaccinated. There was no significant correlation between level of education and vaccination status (P=.37). Both COPD-related emergency department and hospital visits were significantly decreased in vaccinated patients with COPD (P<.001 and P=.02, respectively). Of all the subjects, 39.7% (35 of 88 subjects) mentioned that no health-care professional recommended vaccination. CONCLUSIONS: Physicians should be more aware of vaccination and recommend both influenza and pneumococcal vaccines to all patients with COPD to reduce exacerbations.

Adherence to GOLD guideline treatment recommendations among pulmonologists in Turkey.

BACKGROUND: Low adherence to Global initiative for chronic Obstructive Lung Disease (GOLD) guideline recommendations has been reported worldwide. There has been no study on the adherence to GOLD guidelines for COPD treatment in Turkey. OBJECTIVES: To investigate the rates of adherence to GOLD 2010 guidelines for COPD treatment among pulmonologists. DESIGN: A multi-center, cross-sectional, observational study was carried out in eleven pulmonary outpatient clinics across Turkey. Adherence to GOLD was evaluated through hospital records. Demographic and clinical data were recorded. RESULTS: Study included 719 patients (mean age: 62.9±9.7 years; males 85.4%) of whom 16 was classified as GOLD Stage I, 238 as II, 346 as III, and 119 as IV, and only 59.5% received appropriate treatment. Rates of guideline adherence varied across GOLD stages (I, 6.3%; II, 14.7%; III, 84.4%; and IV, 84%). Causes of inappropriate therapies were overtreatment (Stage I, 100% and Stage II, 91.1%), undertreatment (Stage III, 3.3% and Stage IV, 10.9%) and lack of treatment (Stage II, 3.8%; Stage III, 2.3%; and Stage IV, 5.9%). The most preferred regimen (43.4%) was long-acting ß2-agonist-inhaled corticosteroid-long-acting muscarinic antagonist. Overall, 614 patients (89%) received treatment containing inhaled corticosteroid. CONCLUSION: Pulmonologists in Turkey have low rates of adherence to GOLD guidelines in COPD treatment. Inappropriateness of therapies was due to overtreatment in early stages and excessive use of inhaled corticosteroid (ICS) in all disease stages.

Prognostic factors affecting survival in malignant pleural mesothelioma: analysis of 125 subjects.

AIM OF THE STUDY: Determining the pre-treatment prognostic factors in malignant pleural mesothelioma is important in terms of estimating the course of the disease and selecting patients who are candidate for multimodal therapy. The aim of the study was to determine the prognostic factors affecting survival in patients with malignant pleural mesothelioma. STUDY DESIGN: One hundred and twenty-five patients who had been diagnosed histologically as having malignant pleural mesothelioma over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC) and serum LDH values, histology, performance score and stage of disease were examined. RESULTS: Advanced clinical stage, N2 nodal involvement and the presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be a poor prognostic factor independently of other factors. CONCLUSIONS: We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate for multimodal treatment and in estimating the prognosis.

Smoking and prognostic factors in an observational setting in patients with advanced non-small cell lung carcinoma.

BACKGROUND: This prospective observational study estimated the effect of prognostic factors, particularly continued smoking during therapy, on survival in advanced non-small cell lung cancer (NSCLC) patients receiving gemcitabine-platinum. Further, prognostic factors were used to build a survival model to improve prognosis prediction in naturalistic clinical settings. METHODS: Eligibility criteria included: Stage IIIB/IV NSCLC, no prior chemotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. A Cox regression model was constructed and validated by randomizing patients into two datasets (Construction [C]:Validation [V]; 3:1 ratio). Country, disease stage, hypercalcemia, "N" factor, weight reduction, performance status, and superior vena cava obstruction were pre-defined variables forced into the model. Continued smoking was tested with adjustment for these variables. RESULTS: One thousand two hundred and fourteen patients (C=891 and V=323) were enrolled. The final predictive model, established in the Construction dataset, identified four significant (p≤0.05) and independent predictors of survival, which were disease stage, performance status, gemcitabine-platinum regimen, and T-stage. Smoking during therapy was not significantly associated with survival (Hazard Ratio [95% CI]: 0.955 [0.572, 1.596], p=0.8618; versus never smokers). CONCLUSIONS: Although continued smoking during therapy was not significantly associated with shorter survival, the model developed in this study forms an evidence-based approach to assessing prognosis in advanced stage NSCLC.

[Pre-treatment and treatment-induced neuron-specific enolase in patients with small-cell lung cancer: an open prospective study]. / Valores pretratamiento e inducidos por el tratamiento de enolasa específica de neurona en pacientes con cáncer de pulmón microcítico: estudio prospectivo, abierto.

BACKGROUND: Neuron-specific enolase (NSE) is the most sensitive tumor marker for small-cell lung carcinoma (SCLC) at the time of diagnosis. The main purpose of this study was to review the usefulness of serum NSE level as a prognostic factor in patients with SCLC and to determine the correlation between the NSE level and the stage of disease and response to chemotherapy. METHODS: In this prospective study, patients with SCLC were evaluated for response to chemotherapy, survival without disease progression, and overall survival. The end point was designated at patient death due to SCLC. NSE assays were performed before and after completion of chemotherapy. RESULTS: Sixty-five patients were included in study. NSE levels were significantly higher in patients who died of SCLC. The pre-treatment NSE levels in patients who responded to treatment were significantly lower. The post-treatment NSE levels were not significantly correlated with response to chemotherapy, progression-free survival, overall survival, and prognosis of patients. Change in the NSE level between the pre- and post-treatment periods was not significantly correlated with response to treatment, progression-free survival, and overall survival. CONCLUSIONS: NSE levels might not be related with the stage of the disease. However, a low pre-treatment NSE level might be used in predicting good response to chemotherapy in patients with SCLC. The post-treatment serum NSE levels and the rate of change between pre- and post-treatment serum levels of NSE were not related with response to chemotherapy, progression-free survival, and overall survival.