Potential role of pre-treatment bone marrow SUVmean to liver SUVmean ratio (BM/L) and comparison of primary tumour FDG uptake with brain FDG uptake in predicting survival in limited-stage lung cancers.

INTRODUCTION: The survival rates of patients with limited-stage small-cell lung cancer are low despite curative treatment. Accordingly, we investigated the disease prognosis by comparing the pre-treatment bone marrow mean standardised uptake values (SUVmean) / liver SUVmean ratio (BM/L) and primary tumour FDG uptake and brain FDG uptake to prognosis. MATERIALS AND METHODS: This was an observational, retrospective, single-centre study of patients with limited-stage small-cell lung cancer. Maximum standardised uptake values before treatment SUVmax, mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), liver (KC) SUVmean, bone marrow SUVmean, BM/L ratio (grouped as BM/L <1 and BM/L<1), FDG uptake level of the primary tumour are higher than brain FDG uptake. The association of low prevalence with overall survival (OS) and progression-free survival (PFS) was evaluated. DISCUSSION: A total of 125 patients were included in the study. The risk of death was found to be two times higher in patients with primary tumour FDG uptake higher than brain FDG uptake compared to those with less brain involvement. The risk of death in patients with BM/L>1 was found to be 1.6 times higher than in patients with BM/L<1. CONCLUSION: Comparison of BM/L, FDG uptake of the primary tumour and brain FDG uptake as new prognostic parameters can be guiding in the classification of patients with LD-SCLC with a higher risk of death or progression and in planning new treatment strategies.

Characteristics of our hypoxemic COVID-19 pneumonia patients receiving corticosteroids and mortality-associated factors.

BACKGROUND: COVID-19 is a disease associated with diffuse lung injury that has no proven effective treatment yet. It is thought that glucocorticoids may reduce inflammation-mediated lung injury, disease progression, and mortality. We aimed to evaluate our patient's characteristics and treatment outcomes who received corticosteroids for COVID-19 pneumonia. METHODS: We conducted a multicenter retrospective study and reviewed 517 patients admitted due to COVID-19 pneumonia who were hypoxemic and administered steroids regarding demographic, laboratory, and radiological characteristics, treatment response, and mortality-associated factors. RESULTS: Of our 517 patients with COVID-19 pneumonia who were hypoxemic and received corticosteroids, the mortality rate was 24.4% (n = 126). The evaluation of mortality-associated factors revealed that age, comorbidities, a CURB-65 score of ≥ 2, higher SOFA scores, presence of MAS, high doses of steroids, type of steroids, COVID-19 treatment, stay in the intensive care unit, high levels of d-dimer, CRP, ferritin, and troponin, and renal dysfunction were associated with mortality. CONCLUSION: Due to high starting and average steroid doses are more associated with mortality, high-dose steroid administration should be avoided. We believe that knowing the factors associated with mortality in these cases is essential for close follow-up. The use of CURB-65 and SOFA scores can predict prognosis in COVID-19 pneumonia.

Small cell lung cancer stem cells display mesenchymal properties and exploit immune checkpoint pathways in activated cytotoxic T lymphocytes.

Small cell lung cancer (SCLC) is an aggressive tumor type with early dissemination and distant metastasis capacity. Even though optimal chemotherapy responses are observed initially in many patients, therapy resistance is almost inevitable. Accordingly, SCLC has been regarded as an archetype for cancer stem cell (CSC) dynamics. To determine the immune-modulatory influence of CSC in SCLC, this study focused on the characterization of CD44+CD90+ CSC-like subpopulations in SCLC. These cells displayed mesenchymal properties, differentiated into different lineages and further contributed to CD8+ cytotoxic T lymphocytes (CTL) responses. The interaction between CD44+CD90+ CSC-like cells and T cells led to the upregulation of checkpoint molecules PD-1, CTLA-4, TIM-3, and LAG3. In the patient-derived lymph nodes, CD44+ SCLC metastases were also observed with T cells expressing PD-1, TIM-3, or LAG3. Proliferation and IFN-γ expression capacity of TIM-3 and LAG3 co-expressing CTLs are adversely affected over long-time co-culture with CD44+CD90+ CSC-like cells. Moreover, especially through IFN-γ secreted by the T cells, the CSC-like SCLC cells highly expressed PD-L1 and PD-L2. Upon a second encounter with immune-experienced, IFN-γ-stimulated CSC-like SCLC cells, both cytotoxic and proliferation capacities of T cells were hampered. In conclusion, our data provide evidence for the superior potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade immunotherapy .

Clinical management of lung cancer patients with respiratory symptoms during the COVID-19 pandemic.

OBJECTIVE: There are many clinical conditions, such as lung cancer, that need to be followed up and treated during a pandemic. Providing health care for patients who are immune-suppressive requires extra care. METHOD: Among 108 lung cancer patients who had been hospitalized during the COVID-19 pandemic, 18 with respiratory symptoms were evaluated retrospectively. RESULTS: The patients' median age was 64 ± 9.4 with a male predominance (male n = 16, female n = 2). Thirteen had non-small cell lung cancer (NSCLC), and 5 had small cell lung cancer (SCLC). Nine (50%) patients were receiving chemotherapy. The most common symptom was shortness of breath (n = 14, 77.8%), followed by fever (n = 10, 55.6%). The findings confirmed on computed thorax tomography (CTT) were as follows: consolidation (n = 8, 44.4%), ground glass opacities (n = 8, 44.4%) and thoracic tumour/mediastinal-hilar lymphadenopathy (n = 3, 16.7%). Hypoxia was seen in 11 patients (61.1%), twelve patients had an elevated LDH (median = 302 ± 197) and lymphopenia (median = 1055 ± 648) and 5 (27.7%) were highly suspected of having contracted COVID-19. None of their nasopharyngeal swaps was positive. Two of these 5 patients received COVID-19 specific treatment even though they thrice had negative reverse transcription polymerase chain reaction (RT-PCR) results. The two patients responded well to both clinical and radiological treatments. For one case with SCLC receiving immunotherapy, methylprednisolone was initiated for radiation pneumonitis after excluding COVID-19. CONCLUSION: In line with a country's health policies and the adequacy of its health system, the necessity of a multidisciplinary approach in the management and treatment of complications in patients with lung cancer has become even more important during the COVID-19 pandemic.

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.

Effect of Asbestos Exposure on the Frequency of EGFR Mutations and ALK/ROS1 Rearrangements in Patients With Lung Adenocarcinoma: A Multicentric Study.

OBJECTIVE: The aim of this study is to investigate the effect of asbestos exposure on cancer-driver mutations. METHODS: Between January 2014 and September 2018, epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and c-ros oncogene 1 receptor tyrosine kinase gene (ROS1) alterations, demographic characteristics, asbestos exposure, and asbestos-related radiological findings of 1904 patients with lung adenocarcinoma were recorded. RESULTS: The frequencies of EGFR mutations, ALK, and ROS1 rearrangements were 14.5%, 3.7%, and 0.9%, respectively. The rates of EGFR mutations and ALK rearrangements were more frequent in asbestos exposed non-smokers (48.7% and 9%, respectively). EGFR mutation rate was correlated to female gender and not-smoking, ALK rearrangement rate was correlated to younger age, not-smoking, and a history of asbestos exposure. CONCLUSIONS: The higher rate of ALK rearrangements in asbestos-exposed lung adenocarcinoma cases shows that asbestos exposure may most likely cause genetic alterations that drive pulmonary adenocarcinogenesis.

The Clinical Impact of Re-biopsies in Lung Adenocarcinoma: a Retrospective Multicenter Study.

If a patient's cancer progresses while undergoing targeted therapy, a re-biopsy is not mandatory. But when evaluating the benefits and risks on a case-by-case basis (transformation to small cell, assessing for a clinical trial), physicians should inform patients about the possible need for a re-biopsy (5). This was a retrospective and multicentre study. A total of 644 patients with lung adenocarcinoma were reviewed, 625 of whom were ruled eligible. From them, 399 were found to show disease progression, and 126 re-biopsies were performed. Progression status, re-biopsy sites, success of obtaining adequate tissue, molecular patterns after re-biopsy and subsequent treatments were analysed. Survival differences among patients with disease progression were then examined according to re-biopsy status. Overall, 625 patients with adenocarcinoma and a median age of 61.4 were evaluated. Initial tyrosine kinase inhibitor (TKI) usage numbered 37 patients (5.9%). Progression was diagnosed in 399 (63.8%) patients, out of which 26 (31.6%) underwent re-biopsies. The successful number of re-biopsies was 103 (81.7%). No complications were observed after any of the biopsy procedures. Subsequent treatments were changed in 15 patients (11.9%), who began new TKI treatments. Poor performance status was the most common reason for not performing a biopsy (n = 65; 23.8%), followed by the physician's decision (n = 40; 14.6%). Re-biopsies can demonstrate the new characteristics of a tumour and can detect the activation of pre-existing clones, making possible new treatment opportunities for patients. According to the performance status of the patient and the availability of the progressive lesion, we should increase the rate of re-biopsies before the decision to follow up with the best supportive care.

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.

Complications of silicone Y stents placed due to malignant airway stenosis.

INTRODUCTION: Malignant central airway obstruction around the main carina often requires placement of Y­shaped stents. In this study, we aimed to determine the safety of silicone Y stents placed around the main carina in the malignant airway obstruction by examining the long term complications, emergence times and treatment approaches of complications. MATERIALS AND METHODS: Between May 2012 and July 2015, 47 silicone Y stents were placed in 46 patients with malignant external compression or mixed type stenosis around the main carina. Patient stents were placed via rigid bronchoscopy under total intravenous anesthesia in operating room conditions. RESULT: In the half of the patients (23/46), stents were placed under urgent conditions due to acute respiratory failure. Stents were deployed successfully in all the patients. No procedure related deaths were observed. The median time of survival following stent insertion was 157 days. The total long-term complication rate of silicone Y stents was 28.3%. Mucostasis (8.7%) and migration (2.2%) were observed within the first month after placement of the silicone Y stents (median 18 days), stent-edge granulation tissue development (13.0%) was observed at the earliest one month (median 64, range 34-386 days) and stent-edge tumor tissue development (4.3%) were observed at the earliest 3 months (median 151, range 85-217 days). A total of 7 (15.2%) stents were removed, 2 of which were due to mucostasis and 5 of which were due to granulation tissue development. One patient's stent was replaced with a longer silicone Y stent due to stent-edge tumor tissue development. CONCLUSIONS: The best palliative treatment of malignant tumor stenosis around the main carina is still silicone Y stent placement, but the long-term complication rate can be high. For this group of patients, bronchoscopy to be performed at the first and third months after silicone Y stent placement may provide early detection of stent-edge tissue development.

Comparison of two new techniques for the management of malignant central airway obstruction: argon plasma coagulation with mechanical tumor resection versus cryorecanalization.

BACKGROUND: The development of central airway obstruction during malignant diseases is an important cause of morbidity and mortality. Endobronchial therapies can decrease the patient's symptoms and improve quality of life. Here, we compare airway recanalization methods: argon plasma coagulation with mechanical tumor resection (APC + MTR) and cryorecanalization (CR efficiency, complications, restenosis rate, and time to restenosis) in patients with malignant exophytic endobronchial airway obstruction. METHODS: A total of 89 patients were included who were admitted to our hospital between 2005 and 2012. The data were analyzed retrospectively. Initially, a CR procedure was performed in 52 patients using rigid bronchoscopy under general anesthesia; the APC + MTR procedure was performed in 37 patients with malignant airway obstruction. RESULTS: The airway patency rate with APC + MTR was 97.3% (n = 36) and CR was 80.8% (n = 42). The APC + MTR procedure was more effective than CR for recanalization of malignant endobronchial exophytic airway obstruction. Additionally, the achievement rate of airway patency with APC + MTR was significantly higher in tumors with distal bronchial involvement. There was no statistically significant difference between groups in terms of complications, restenosis rate, and time to restenosis. CONCLUSIONS: The APC + MTR procedure is preferred over CR to introduce and maintain airway patency in patients with malignancy-related endobronchial exophytic airway obstruction.

How many samples would be optimal for endobronchial cryobiopsy?

BACKGROUND: Cryobiopsy, which provides larger specimens without crush artifact, is a good option for the diagnosis of visible endobronchial tumors. While there are several papers on diagnostic performance, application protocols vary between centers. In this study, we aimed to find the optimal number of cryobiopsies in endobronchial tumors. METHODS: We prospectively involved cases with a visible endobronchial tumor in which conventional diagnostic measures failed and/or a therapeutic interventional bronchoscopy was planned. Endobronchial tumor was visualized, and four cryobiopsies were taken with a dedicated flexible probe. The samples were evaluated by a pathologist who was blinded to the order of the biopsies. The cumulative performances of one to four cryobiopsies were compared, and a complication analysis was conducted. RESULTS: A total of 50 patients were involved. Four cryobiopsies were taken from 49 patients, and a single biopsy was taken from one case. The sensitivities of one, two, three and four biopsies were 82, 93.9, 93.9 and 95.9 %, respectively. The difference in performance of one and two biopsies was significant (p = 0.031), but the third and fourth biopsies were found to be unnecessary (p = 1.0 for second versus third and p = 1.0 for second versus fourth). Bleeding risk increased when ≥3 cryobiopsies were taken (Odds Ratio 2.758). CONCLUSIONS: When the diagnostic benefits and complication rates were considered, two cryobiopsies were found to be optimal for endobronchial tumors. In patients with non-diagnostic conventional bronchoscopy, endobronchial tumors may be diagnosed by cryobiopsy.