Comparison of Alectinib/Crizotinib Data in First-Line Therapy in Patients with Anaplastic LymphomakinasePositive Nonsmall Cell Lung Carcinoma with Poor Prognostic Features for Alectinib.

OBJECTIVE: Alectinib has a much better central nervous system transmission than crizotinib in patients diagnosed with anaplastic lymphoma kinase mutation-positive nonsmall cell lung carcinoma. We aimed to investigate alectinib's efficacy in the treatment and its place in the first-line treatment and report our real-life data. MATERIAL AND METHODS: The data of 38 patients who were diagnosed with anaplastic lymphoma kinase-positive nonsmall cell lung carcinoma in our clinic between 2016 and 2021, who did not receive any treatment before were retrospectively analyzed. RESULTS: Of the 19 patients who received alectinib, 14 had multiple, and 6 had pretreatment brain metastases. No newly emerging brain metastases were detected during the treatment period. The progression-free survival of patients was 23.5 ± 4.2 months, and overall survival was 24.6 ± 4.1 months. Progression was observed in 10 (52.6%) patients. Of the 19 patients who received crizotinib, 7 had multiple metastases, and brain metastases were detected in 1 patient before treatment and 6 patients during the treatment period. Progression-free survival of crizotinib patients was 17.1 ± 4.8 months and their overall survival was 26.5 ± 6.1 months. Progression was observed in 17 (89.5%) patients. The second line of alectinib could be given to 8 of these patients. Overall survival after second-line treatment of alectinib was 18.2 ± 7.0 months. Overall survival of the patients who could not receive second-line treatment of alectinib was 4.0 ± 2.0 months. CONCLUSION: The progression rate was lower in alectinib than the crizotinib patients, although there were more patients with multiple metastases and brain metastases in the alectinib arm.

Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study.

OBJECTIVES: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. RESULTS: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323). CONCLUSION: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.

Efficiency and Reliability of Bronchoscopic Lung Volume Reduction Coil Application in Patients with Severe Emphysema.

Objectives: In the past years, surgery has been used for the non-medical treatment of severe emphysema. However, in recent years, bronchoscopic lung volume reduction (LVR) treatment has become more preferred because it is less invasive. Bronchoscopic coil treatment is the most frequently applied technique among these methods. The aim of the investigation was to determine the efficacy and safety of bronchoscopic volume reduction coil treatment for patients with severe emphysema. Methods: The patients who were performed bronchial volume reduction coil treatment between 2015 and 2017 and were followed in our outpatient clinic were retrospectively examined. They were followed for 1 year at quarterly intervals after the procedure. All the safety and efficacy of the patient's records, including the modified Medical Research Council (MRC) dyspnea score, the St. George's Respiratory Questionnaire (SGRQ) quality of life scale, the 6 min walk distance (6-MWT), pulmonary function tests, and adverse events, were evaluated. Results: Sixteen patients were included in the study. The mean of the preoperative mMRC clinic dyspnea score was 3.38, the mean of the 3rd month's mMRC score was 2.62 (p=0.007), and the mean of the 12th month's mMRC was 2.37 (p=0.003). The preoperative SGRQ quality of life parameter was 71.95±15.7, the 3rd month was 66.7±16.2 (p=0.007), and the 12th month was 62.9±16.4 (p=0.003). Preoperative mean of 6-MWT was 247.25±112.36 m, 3rd month 264.25±95 m (p=0.148), and 12th month 317±122.9 m (p=0.034). Patients' preoperative residual volume was 5.28±1.96 L, 3rd month 4.52±1.35 L (p=0.023), and 12th month 4.545±1.83 L (p=0.163). Patients' preoperative forced expiratory volume in one second, respectively, was 0.79±0.29 L, 3rd month 0.79±0.3 L (p=0.917), and 12th month 0.86±0.3 L (p=0.756). Conclusion: It seems that bronchoscopic LVR coil treatment, which is an effective and reliable procedure that reduces shortness of breath rather than respiratory function test parameters and improves the quality of daily life, will become even more widespread.

IMPORTANCE of PRETREATMENT 18F-FDG PET/CT TEXTURE ANALYSIS in PREDICTING EGFR and ALK MUTATION in PATIENTS with NON-SMALL CELL LUNG CANCER.

OBJECTIVE: Identification of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutation types is of great importance before treatment with tyrosine kinase inhibitors (TKIs). Radiomics is a new strategy for noninvasively predicting the genetic status of cancer. We aimed to evaluate the predictive power of 18F-FDG PET/CT-based radiomic features for mutational status before treatment in non-small cell lung cancer (NSCLC) and to develop a predictive model based on radiomic features. METHODS: Images of patients who underwent 18F-FDG PET/CT for initial staging with the diagnosis of NSCLC between January 2015 and July 2020 were evaluated using LIFEx software. The region of interest (ROI) of the primary tumor was established and volumetric and textural features were obtained. Clinical data and radiomic data were evaluated with machine learning (ML) algorithms to create a model. RESULTS: For EGFR mutation prediction, the most successful machine learning algorithm obtained with GLZLM_GLNU and clinical data was Naive Bayes (AUC: 0.751, MCC: 0.347, acc: 71.4%). For ALK rearrangement prediction, the most successful machine learning algorithm obtained with GLCM_correlation, GLZLM_LZHGE and clinical data was evaluated as Naive Bayes (AUC: 0.682, MCC: 0.221, acc: 77.4%). CONCLUSIONS: In our study, we created prediction models based on radiomic analysis of 18F-FDG PET/CT images. Tissue analysis with ML algorithms are non-invasive methods for predicting ALK rearrangement and EGFR mutation status in NSCLC, which may be useful for targeted therapy selection in a clinical setting.

The Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Predicting Treatment Response Before EGFR TKI Treatment in Patients with Advanced Lung Adenocarcinoma.

Objectives: This study makes a retrospective examination of exploring the prognostic value of 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) related metabolic-volumetric variables, nutritional status, and immune and inflammatory markers on progression-free survival (PFS) and overall survival (OS) in advanced adenocarcinoma patients with positive epidermal growth factor receptor (EGFR) mutations undergoing EGFR tyrosine kinase inhibitor (TKI) therapy. Methods: A retrospective examination was made of patients diagnosed with lung adenocarcinoma who underwent 18F-FDG PET/CT imaging for staging maximum four weeks before starting treatment, between January 2015 and July 2020. Included in the study were 68 patients identified histopathologically to have locally advanced/metastatic EGFR mutation-positive adenocarcinoma, and who underwent EGFR TKI therapy. The laboratory data of the patients, obtained 15 days before imaging performed for PET/CT staging, were evaluated. Results: Metabolic tumor volume, modified Glasgow prognostic score and locally advanced disease were identified as independent prognostic parameters for PFS (p=0.004, p=0.029, p=0.016, respectively). A univariate Cox regression analysis revealed albumin/alkaline phosphatase and tumor size to be significant parameters for prognosis (p=0.033, p=0.043, respectively). A multivariate Cox regression analysis revealed that none of the parameters were predictive or OS. Conclusion: The parameters of 18F-FDG PET/CT, especially the volumetric parameters, were found to be strong prognostic factors with statistical significance for predicting PFS. We believe that these parameters are important prognostic markers that should be evaluated together in the management and follow-up of patients with EGFR mutation-positive adenocarcinoma.

Complication and cost analysis of transbronchial lung cryobiopsy and awake video-assisted thoracic surgery in diagnosis of interstitial lung disease.

Aim and introduction: Diagnosing of interstitial lung disease (ILD) is difficult and expensive. The standard diagnostical approaches to ILD are bronchoalveolar lavage, transbronchial lung biopsy, transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB). SLB is gold standard for the confident diagnosis of ILD but because of the poor performance of the patients it's use is limited. We conducted a retrospective study to point out that TBLC plays an important role in diagnosis of ILD and has fewer complications and lower cost than awake video-assisted thoracic surgery (AVATS). Material and methods: 132 patients who underwent TBLC and AVATS with a pre-diagnosis of ILD in our hospital between 2015 and 2020 were evaluated retrospectively. Diagnosis rates, complications and costs were recorded. Results: There were no non-diagnostic materials in 44 patients in AVATS arm. Prolonged air leak was observed in 11(25.0%) of the patients, and six of them (13.6%) were discharged with Heimlich Valve (HV). Median length of stay in the hospital was 8 days, while average patient cost was $515.9 (415.2-2662.9) in the AVATS arm. Non-diagnostic material was obtained from 10 (11.3%) of 88 patients in TBLC arm. Six (6.8%) of them had pneumothorax, only one of them required a chest tube. No patient was discharged with HV (p=0.001). Median cost for each patient with a median hospital stay of 2.0 (1.0-21.0) (p<0.001) days was $171.9 (80.8-1493.3) (p<0.001). Discussion: Although TBLC is behind AVATS in terms of diagnostic accuracy, it may be an alternative diagnostic tool in the diagnosis of interstitial lung disease due to its acceptable safety profile and cost-effectiveness.

PDL-1 Expression and Survival in Metastatic Non-small Cell Lung Cancer Patients Who Received Chemotherapy as First-Line Treatment.

OBJECTIVE: To show the effect of programmed cell death protein-1ligand (PDL-1) level on survival times in patients with metastatic non-small cell lung cancer (mNSCLC) receiving chemotherapy, to determine the relationship between PDL-1 level, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). MATERIAL AND METHODS: The data of 158 patients who received chemotherapy for mNSCLC were evaluated retrospectively. Clinical and demographic data, PDL-1 expression levels and follow-up periods of the patients were recorded. The patients were divided into 2 groups according to PDL-1 levels. RESULTS: In all patients, progression free survival (PFS) was 5.6 months and overall survival (OS) was 18.8 months. Patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.038). In the gemcitabine and taxane groups, patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.047). There was a significant correlation between NLR and PDL-1 levels. In the groups with high PDL-1, patients with low NLR levels had higher OS than patients with high NLR level (p:0.043). Also, there was a significant difference between the OS patients with low and high PLR levels (p:0.520). CONCLUSION: In patients with mNSCLC whose PDL-1 levels and NLR levels are low, immunogenic chemotherapies such as gemcitabine and taxane can be tried as an alternative treatment.

Efficacy, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar) versus Reference Bevacizumab in Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study (STELLA).

BACKGROUND: MB02 (bevacizumab biosimilar) showed similar structural, functional, and pharmacokinetic properties to reference bevacizumab (Avastin®; EU-bevacizumab). OBJECTIVES: To confirm clinical similarity between MB02 and EU-bevacizumab, a comparability study was undertaken in the first-line treatment of stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This multinational, double-blind, randomized, phase III study (STELLA) compared MB02 or EU-bevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18), followed by MB02/EU-bevacizumab in blinded monotherapy until disease progression, unacceptable toxicity, death, withdrawal of consent or end of study (Week 52). The primary efficacy endpoint was objective response rate (ORR) evaluated by an independent radiological review committee (IRC) at Week 18 (intent-to-treat population). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and immunogenicity. RESULTS: A total of 627 subjects were randomized 1:1 to MB02 (n = 315) or EU-bevacizumab (n = 312). ORR, assessed by the IRC at Week 18, was comparable in MB02 (40.3%) and EU-bevacizumab (44.6%) groups. ORR risk ratio of 0.910 (90% CI 0.780 to 1.060; 95% CI 0.758 to 1.092) and ORR risk difference of -4.02 (90% CI -10.51 to 2.47; 95% CI -11.76 to 3.71) were within the similarity predefined margins. There were no significant differences between MB02 and EU-bevacizumab groups in median PFS (36.0 vs 37.3 weeks, respectively; HR 1.187; 95% CI 0.98 to 1.44) and median OS (not achieved; HR 1.108; 95% CI: 0.83 to 1.49) at the end of study. The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable. The most frequent grade ≥3 investigational-product-related AEs were hypertension and anemia, with a difference between treatment groups of <5%. Anti-drug antibodies (ADA) and neutralizing ADA (NAb) incidence were similar in both treatment groups. CONCLUSION: MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles. CLINICAL TRIAL REGISTRATION: EudraCT No. 2017-001769-26; ClinicalTrials.gov: NCT03296163.

Diagnostic efficacy of EBUS-TBNA in benign diseases in a population with a high prevalence of tuberculosis.

SETTING: Although endobronchial ultrasonography-transbronchial needle aspiration (EBUS-TBNA) has a well-known place in the staging and diagnosis of lung cancer, the place of EBUS is not clear in the diagnosis of benign diseases, especially in countries with a high prevalence of tuberculosis. AIM: The aim of this study is to investigate the diagnostic efficacy of EBUS-TBNA in benign diseases in a population with a high prevalence of tuberculosis. MATERIAL AND METHODS: Between October 2011 and March 2018, 1077 EBUS-TBNA was applied. RESULTS: The diagnosis was reached with mediastinoscopy or video assisted thoracic surgery (VATS) in 41 (74.5%) and with the second EBUS-TBNA performed in 14 (25.5%) of 55 EBUS practices in 41 patients with malignancy diagnosis. The final diagnosis was achieved with clinical/radiological features in 7 (77.7%) cases of sarcoidosis, with VATS/mediastinoscopy in 2 (22.2%) cases, with EBUS-TBNA performed for the second time in 6 (54.5%) tuberculosis cases and with acid-resistance bacilli reproduction in Lowenstein-Jensen culture in 5 (45.4%) cases. Two hundred and ninety-five (79.7%) patients were accepted as "benign disease" due to the absence of radiological and clinical progression of lesions in the follow-up. CONCLUSION: The diagnostic accuracy of EBUS-TBNA is high in benign diseases such as sarcoidosis and tuberculosis.

Diagnostic approach in parenchymal lung diseases: transbronchial lung biopsy or cryobiopsy?

Background/aim: Diagnosis of interstitial lung diseases requires a multidisciplinary approach, and a gold standard for histological diagnosis is open lung biopsy. Transbronchial lung biopsy (TBLB) and in recent years an alternative method, cryobiopsy (TBLC), are used for the diagnosis of parenchymal lung lesions. The aim of this study is to compare the efficacy of concomitant conventional TBLB and TBLC. Materials and methods: A total of 82 patients who underwent TBLC for diagnosis of diffuse parenchymal lung diseases at Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital between 2015 and 2018 were screened retrospectively and included in the study. Of the patients, 53.7% (n: 44) were male, and 46.4% (n:38) of them were female. The mean age was 58.37 (±9.33) years. First TBLB and then TBLC were performed to all patients in the same session and their diagnostic performances were compared. Results: Although both procedures were done in the same session, 45 patients (54.9%) were diagnosed with TBLB and 75 patients (91.5%) were diagnosed with TBLC (P ˂ 0.001). Hemorrhage was observed in 39 patients (47.6%), but only one had a massive hemorrhage. Pneumothorax was observed in 6 patients (7.3%) and none of them required tube drainage. Conclusion: Transbronchial lung cryobiopsy is a promising technique for the diagnosis of parenchymal lung diseases compared to transbronchial lung biopsy.

Pseudomesotheliomatous Primary Squamous Cell Lung Carcinoma: The First Case Reported in Turkey and a Review of the Literature.

In rare cases, pseudomesotheliomatous tumors spread diffusely within the pleura to form an encasing mass, which may be confused with diffuse malignant mesothelioma (DMM). A 73-year-old male presented with chest pain, dyspnea and a significant loss of weight and appetite. His radiological and clinical features suggested DMM. However, immunohistochemical studies revealed a primary squamous cell cancer of the lung. To the best of our knowledge, this is the first case report of pseudomesotheliomatous primary squamous cell lung cancer in Turkey, and also the seventh case worldwide. The present report aims to present this case, along with a review of the medical literature.

Four cases of pulmonary thromboembolism diagnosed by endobronchial ultrasound.

Endobronchial ultrasound (EBUS) is a technique for the detection of mediastinal abnormalities. A total of 548 EBUS procedures were performed for various indications, and in four cases (0.7%), filling defects in central pulmonary arteries were demonstrated fortuitously during the procedure. Subsequently, all patients underwent contrast-enhanced CT of the thorax to confirm the diagnosis of pulmonary thromboembolism (PTE). In three of the four cases, there was a concomitant lung cancer. PTE can be incidentally detected during EBUS; therefore, pulmonary arteries should be examined carefully during EBUS in all patients, particularly in patients with suspected or proven malignancy. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:441-444, 2017.

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.

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.