Could PD-L1 positivity be associated with venous thrombosis in patients with non-small cell lung cancer?

The risk of venous thromboembolism (VTE) is increased in non-small cell lung cancer (NSCLC), and defining at-risk patients is important. Thus, we aimed to assess the association between programmed cell death ligand 1 (PD-L1) expression and VTE [pulmonary embolism (PE), deep venous thrombosis (DVT)] in NSCLC. In this retrospective, observational multicentre study, 369 patients with NSCLC who had PD-L1 immunohistochemistry based on biopsies taken between January 2017 and December 2019, were divided as PD-L1-positive (n = 181) and -negative (n = 188) groups, and low-positive (n = 99) and high-positive (n = 82) PD-L1 groups. Among all population, 12.5% of them developed a VTE during a median follow-up of 474 days. The rates of DVT, PE, and PE + DVT were 5.7%, 6% and 0.8%, respectively. VTE (15.5% vs. 9.5%) and DVT (3.8% vs. 7.4%) were similar between two groups, while PE was significantly higher in PD­L1-positive group than those in PD-L1-negative group (11.1% vs 1%, p < 0.001). There were no significant differences between low- and high-positive groups in terms of VTE (14.1% vs. 17%), PE (12.1% vs. 9.8%), and DVT (2% vs. 6.1%). In the multivariate analysis, multiple metastases (Hazard ratio [HR] 4.02; 95% confidence interval [Cl] 1.18-13.63; p = 0.07) and PD-L1 positivity was associated with an increased PE risk (HR 8.39; 95% Cl 2.07-34.07; p = 0.003). In conclusion, PD-L1 positivity may be of important role in predicting the increased risk of PE in patients with NSCLC and thereby may be used to define patients likely to benefit from thromboprophylaxis.

Evaluation of Exudative Pleural Effusions: A Multicenter, Prospective, Observational Study.

PURPOSE: The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers. METHODS: This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy. RESULTS: The mean age ± SD of the 777 patients was 62.0 ± 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%). CONCLUSION: The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.

The success of non-invasive mechanical ventilation in lung cancer patients with respiratory failure.

INTRODUCTION AND AIM: Despite the improvement in survival among patients with lung cancer as a result of the development of novel treatment options, acute respiratory failure (ARF), which may occur because of the disease itself, comorbidities or complications in treatment may be life threatening. The most commonly utilised treatment option in cancer patients with ARF is invasive mechanical ventilation (IMV). The prognosis of lung cancer patients admitted to the intensive care unit is poor. The use of non-invasive mechanical ventilation (NIMV) in the setting of ARF not only supports the respiratory muscles and facilitates alveolar ventilation and airway patency, but also reduces the risk of serious complications of IMV, such as ventilator-associated pneumonia. NIMV treatment in the event of respiratory failure has been associated with a high rate of mortality in recently diagnosed or progressive lung cancer with organ failure. However, studies in this regard are limited, and the role of NIMV has yet to be investigated in patients in hospital wards. Accordingly, the present study investigates retrospectively the success of NIMV among patients with lung cancer (including all stages and histopathological types) in a hospital ward setting and the influential factors. MATERIAL AND METHOD: The data of 42 patients with lung cancer and respiratory failure who were admitted to the palliative care service and received NIMV between 2014 and 2018 were reviewed retrospectively. Demographic features, comorbidities, respiratory failure types, rate of withdrawal from NIMV, frequencies of tracheostomy and intubation, bacteriologic examination of the airway samples, rate of discharge from hospital and any history of NIMV/USOT use at home were recorded. NIMV success was defined as the discharge of the patient from the hospital, with or without a respiratory support device. The primary end-point of the study was NIMV success, while the secondary end-point was NIMV success with respect to the underlying diagnosis and respiratory failure type. RESULTS: A total of 42 patients (38 males and 4 females) were included in the study, with a mean age of 67.4 ± 9.5 years. The rate of discharge from hospital was 71% across the entire study population, among which, 13 (31%) were discharged with USOT and 16 (38.1%) with NIMV. Among the 12 patients under palliative supportive treatment, 8 were discharged from the hospital. The success rates of NIMV in the respiratory failure aetiological subgroups were: 66% (12 patients) in the pneumonia subgroup and 71.4% (15 patients) in the COPD subgroup. The difference between these subgroups was not significant (P = .841). The success rate of NIMV in the hypercapnic and hypoxaemic respiratory failure subgroups was 72.7% (24 patients) and 66.6% (6 patients), respectively. There were no significant differences between the type of respiratory failure subgroups (P = .667). The success rate of NIMV was similar in patients with a positive airway sample microbiology (71.4%, n = 14) and those with no growth identified in the culture (70.3%, n = 28) (P = .834). CONCLUSION: In lung cancer patients with no contraindication, NIMV can be used to reduce or postpone the need for ICU admission, independent of disease stage, cellular type and underlying cause.

Comparing effectiveness of intelligent volume-assured pressure support (iVAPS) vs bi-level positive airway pressure spontaneous/timed (BPAP S/T) for hypercapnic respiratory failure in chronic obstructive pulmonary disease.

BACKGROUND AND AIM: Intelligent volume-assured pressure support (iVAPS) is a relatively new hybrid mode of non-invasive ventilation (NIV). There is still limited evidence for iVAPS. The aim of this study was to compare the effectiveness of iVAPS to that of bi-level positive airway pressure spontaneous/timed (BPAP S/T) in patients with acute hypercapnic respiratory failure or acute-on-chronic hypercapnic respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the emergency department. MATERIAL AND METHODS: This was an observational, retrospective study. Eighty-two patients with hypercapnic respiratory failure caused by AECOPD, who were admitted to our emergency department, were analysed. Arterial blood gas (ABG) parameters, length of hospital stay and rate of intensive care unit (ICU) admission were compared between iVAPS and BPAP S/T. RESULTS: A total of 82 patients (26 females, 56 males, mean age 68.26 ± 11.63 years) who were treated with iVAPS (N = 26) or BPAP S/T (N = 56) were enrolled. There were no significant differences between two modes with respect to demographics such as age, gender, presence of comorbidity, usage of long-term oxygen therapy or NIV, and the baseline ABG parameters. The presence of pneumonia was significantly higher in BPAP S/T (P = .01). The rate of ICU admission was 26.9% in iVAPS vs 25% in BPAP S/T. The mean length of hospital stay was 11.5 ± 12.3 days in iVAPS and 9.7 ± 7.4 days in BPAP S/T (P = .53). The mean values of ABG parameters at the 1st and 24th hours of NIV therapy did not differ in both groups. CONCLUSION: Both modes were similarly effective in the management of appropriately selected patients with hypercapnic respiratory failure caused by AECOPD. Hence, we underline that NIV mode selection in the emergency department should be performed in line with experiences of clinicians/institutions and accessibility of ventilator devices/modes.

Association of depression with improper use of inhaler devices by patients with obstructive disease.

INTRODUCTION: Obstructive pulmonary disease may cause some psychiatric disorders such as depression, similar to other chronic diseases. Patients with chronic obstructive pulmonary disease or asthma are especially susceptible to inhaler technique errors. The aim of this study was to evaluate the depression that can affect improper use of inhaler devices and to show the contribution of age, sex, and education to correct usage. MATERIALS AND METHODS: In this study, trained health care workers in the presence of Chest specialist requested patients to demonstrate their inhaler technique and assessed it according to the checklist. If any of the steps were missing or done incorrectly, it was marked as an incorrect technique. RESULTS: We included 188 participants, mean age of 58.3 ± 12.7 years. Significant variables of individual risk were having comorbidities, age, sex, smoking status, and educational level. There was an inverse relationship between education level and incorrect inhaler technique. Even after controlling for age, gender, and education, depressive symptoms were a significant and independent predictor of improper use of inhaler devices. High levels of depressive symptoms were associated with a 22-fold increase (95% confidence interval, 8.9 to 53.5) in the odds of improper use of inhaler devices after adjustment for potential confounders. CONCLUSIONS: As a result, the presence of depression symptoms may increase the improper use of inhaler devices. Further research is needed to determine if screening for and treating depression improves improper use of inhaler devices and obstructive disease outcomes in this population.

Treatment outcomes in oligometastatic non-small-cell lung cancer: A single-centre experience.

BACKGROUND: Even in oligometastatic stage 4 disease, survival rates are higher when curative approaches focus on both the primary tumour and metastasis. So, we aim to analyse our results of oligometastatic disease retrospectively. METHODS: In total, data on 52 non-small-cell lung cancer (NSCLC) patients with limited metastasis (one to three synchronous/metachronous) were retrospectively analysed. All treatment modalities associated with various treatment modalities [surgery, chemoradiotherapy (CRT), supportive care and palliative chemotherapy] were compared in terms of survival. Curative treatment consisted of surgery or CRT (concurrent or sequential). RESULTS: The median overall survival (OS) time was 35.2 ± 4.1 months. Surgery was superior to CRT in terms of OS (36.7 months vs 27.4 months, P > 0.05). Progression-free survival was 29.4 ± 3.9 months, and survival after first progression (SAFP) was 15.6 ± 2.8 months. Patients in whom a metastasectomy was performed had significantly higher rate of SAFP as compared with those who did not have a metastasectomy (20.07 ± 3.8 months vs 7.9 ± 1.7 months P = 0.046). According to pathological type, an adenocarcinoma was associated with better SAFP than a non-adenocarcinoma (23 ± 4.1 vs 6.4 ± 1.5, P = 0.002). The 1- and 2-years OS rates were 67% and 50.4%, respectively. Among the curative treatment group, the OS of patients younger than 65 years (n = 25) was 31 months, whereas that of patients older than 65 years (n = 13) was 22 months (P = 0.88). CONCLUSION: In well-selected NSCLC patients with limited metastasis, survival rates can reach up to 3 years, even in a geriatric population. Clinical N staging and co-morbidity are important prognostic factors.

Prognostic significance of preoperative consolidation to maximum tumour diameter ratio and SUVmax in pathological stage I lung adenocarcinoma.

OBJECTIVES: Consolidation/tumour (C/T) ratio means the maximum diameter of the consolidation is divided by the maximum diameter of the tumour and it is predictive for pathologic subtypes and prognosis after resection of the tumour. The purpose of this study is to clarify impact of C/T ratio along with maximum standardized uptake value (SUV) in pathological stage I lung adenocarcinoma. METHODS: Only patients with pathological stage I lung adenocarcinoma diagnosed by resection were included. Prognostic impact of C/T ratio and SUVmax were analysed by using regression analyses. RESULTS: Totally 156 patients (121 males, 35 females) were evaluated retrospectively. Overall survival (OS) and progression free survival (PFS) were higher in patients with C/T ratio ≥0.5 (OS: 46.3 ± 23.7 vs 30.4 ± 14.6, P = 0.002 and PFS: 43.0 ± 25.4 vs 27.8 ± 15.8, P = 0.005). But PFS and OS curves did not reveal any significant differences with Kaplan-Meier method (P = 0.45 and P = 0.055 respectively). Resection type (limited vs anatomic) and C/T ratio were predictors for OS in multivariate analyses (resection type: HR: 2.21 (1.01-4.83), P = 0.045 and C/T ratio: HR: 0.44 (0.20-0.98), P = 0.045). For PFS, resection type and SUVmax had prognostic significance (resection type: HR: 3.56 (1.64-7.74), P = 0.001 and SUVmax: HR: 1.31 (0.82-2.99), P = .002). CONCLUSION: In pathological stage 1 lung adenocarcinomas, SUVmax and surgery type are important predictors for recurrence rates. For early stage, adenocarcinoma patients with high SUVmax value, tumour size ≥3 cm and high grade subtype, C/T ratio should not be considered significant alone on survival and recurrence.

High serum YKL-40 level is associated with poor prognosis in patients with lung cancer.

INTRODUCTION: YKL-40 is a glycoprotein that plays role in inflammation and malignant processes. High serum YKL-40 levels are associated with short survive in cancer and chronic obstructive pulmonary disease (COPD) is another reason to increase its' level. However, limited knowledges are known in YKL-40 along with lung cancer and COPD. MATERIALS AND METHODS: One hundred patients were involved to study with lung cancer (84 men, 16 women, and median age 62). Results were compared with 30 healthy volunteers. Thirteen patients were small cell lung cancer (SCLC), 87 patients were non-small cell lung cancer (NSCLC). 62% of patients were inoperable. RESULT: Median YKL-40 level was 222.7 ± 114.1 ng/mL in patients and was 144.5 ± 105.7 ng/mL in controls (p< 0.001). Stage, tumour size, lymph node involvement and distant metastasis weren't associated with serum YKL-40 level. Above all cut-off values (133.159 and 162 ng/mL) survival was shorter (p> 0.05). Patients with COPD had worse survive above all cut-off values (p< 0.05), especially according to 133 ng/mL (p= 0.01). CONCLUSIONS: YKL-40 level is useful in lung cancer however it's not related to cell type and prognosis. It is associated with poor prognosis in lung cancer patients with COPD.

Prognostic significance of serum vascular endothelial growth factor and Angiopoietin-2 in patients with lung cancer.

INTRODUCTION: Vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) are major angiogenic mediators in neovascularization process. In current literature both biomarkers are discussed separately and only for non-small cell lung cancer (NSCLC). So in this study we aimed to examine them together for both cell types NSCLC and small cell lung cancer (SCLC). PATIENTS AND METHODS: 100 patients with lung cancer were enrolled to this single center study. 87 of patients were diagnosed with NSCLC including 28 adenocarcinomas and 59 squamous cell cancers and 13 were SCLC. Results were compared with 30 healthy volunteers. Pre-treatment serum VEGF and Ang-2 levels were measured by using ELISA method. RESULTS: While serum Ang-2 levels were higher in patients than healthy controls (23395 pg/mL vs. 4025 pg/mL, p< 0.001), VEGF levels didn't differ (2308 pg/mL vs. 2433 pg/mL, p> 0.05). There was no difference between cases with SCLC and NSCLC in terms of Ang-2. But serum VEGF values were significantly lower in SCLC than NSCLC and control groups. None of these mediators were correlated with cell type, tumor size, TNM staging, performance status and operability. VEGF levels were higher in patients with chronic obstructive pulmonary disease (COPD), but it was not significant. Three cut of values were determined according to sensitivity and specificity by using youden index. They were 8515.73 pg/mL (sensitivity 78%, specificity 76%), 7097 pg/mL (sensitivity 80%, specificity 70%) and 11063.48 pg/mL (sensitivity 76%, specificity 70%). Patients with SCLC had shorter survival time above cut-off values (p> 0.05). VEGF and Ang-2 showed a weak positive correlation (p= 0.1 and r= 0.638). CONCLUSION: In conclusion, serum VEGF wasn't useful to predict lung cancer, prognosis or cell type. Albeit Ang-2 was higher in patients with lung cancer without any effect on survival. Due to the heterogeneity of the studies done with serum measurement Ang-2 on tumor tissue should be more meaningful.