e20620 Background: Immune check-point inhibitors improved survival in patients with NSCLC and no driver mutations. Pembrolizumab, PD-1 inhibitor, compared to standard chemotherapy resulted in higher response rate and significantly longer progression free survival and overall survival in patients with high PD-L1 expression. Methods: Study was conducted at the University Hospital Center Zagreb, Croatia and assessed the real-world efficacy of pembrolizumab in 246 patients with PD-L1-high (PD-L1 expression ≥ 50%) metastatic non-small cell lung cancer (NSCLC). Patients were treated between March 2018 and April 2020, with exclusion criteria of positive EGFR mutations, ALK rearangements and ROS1 fusions. Results: The mean age of patients was 65 years, 69.5% were male and most patients (92.9%) had a history of smoking (52.7% were current smokers, 40.2% were former smokers). The most common histology was adenocarcinoma (67.5%). Brain metastases were present at diagnosis in 21% patients. Efficacy was assesed with median progression-free survival (PFS) of 22 months and a median overall survival (OS) of 32 months. At 12 months, 60.6% of patients were alive without disease progression. The objective response rate (ORR) was 48.1%, with a disease control rate of 75.8%. There was no significant difference in PFS and OS based on tumor type, smoking status, or PD-L1 assessment method. The only statistical significance was observed in mOS between patients with CNS metastases and those without (p = 0.013; HR = 1.80 (1.04-3.15). In 44 patients (18.1%), adverse event led to treatment discontinuation, and in 7 patients (2.9%) led to death. Among these leading to discontinuation, 50% were grade 1 and 2. The most common treatment-related adverse events of any grade causing treatment discontinuation were pneumonitis in 21/44 patients (47.2%) and, dermatitis in 9/44 (20.4%). Among serious adverse events, grade 3-5, pneumonitis was the most common in 6/44 patients (13.6%). Conclusions: Our study showed that pembrolizumab is effective and safe in a real-world setting, with comparable outcomes from clinical trials.

e21188 Background: Inflammatory cells have important effects on tumor development. Systemicinflammation markers can be used as prognostic factors. Numerous studiesshown that high pretreatment neutrophil-to-lymphocyte ratio (NLR) and/or platelet-to-lymphocyte ratio (PLR) levels are potential prognostic predictors for poor progression-free survival (PFS) and overall survival (OS) in NSCLC patients receiving immunotherapy. Methods: We performed a cohort study of patients with metastatic or recurrent NSCLC treated with nivolumab monotherapy in second‐line or further‐line treatment in Clinical hospital centre Zagreb. Pre-treatment NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood. Patients were categorized in two sub-groups according to their NLR and PLR values. In previous meta-analyses it was suggested that significant cut-off value of NLR is NLR < 5 and ≥5 and PLR < 160 and ≥160. We analysed PFS and OS. Results: Overall 105 patients diagnosed with NSCLC were treated with nivolumab. The patients were enrolled from March 2017 until October 2017 and were observed them for disease progression and death until June 1st 2020. Most of the patients were male (71; 67.6%) with median age 60.3 years (36-77). Our patients were selected on the basis of good performance status, so most of them had ECOG PS 0 and 1 (103; 98.1%). Therapy was applied mostly in the second and third line (67; 64%), but even up to seventh line (2; 1.9%). Median duration of therapy was 34.5 weeks (2-149), while median number of doses was 17 (1-69).The median PFS was 7.2 months (95% CI 4.53-9.86). Regardless of previous treatment the mOS was 16.1 months (95% CI 11.26-20.93).We observed median value of NLR 4.08 (IQR 2.44-5.84) and PLR 200 (IQR 127.49-284.72). Patients with low PLR had better overall survival compared to patients with low PLR (mOS 20.5 months vs 11.9 months; 95%CI 14.07-26.92 vs 7.35-16.44; p = 0.039). The same was not as clear in mPFS, tendency of better mPFS was toward low PLR, but it did not reach statistical difference (low PLR mPFS 9.1 months vs high PLR mPFS 6.1 months; p = 0.49).Patients with low NLR had significantly better overall survival compared to patients with high NLR (mOS low NLR 18.2 vs high NLR 10.1 months; 95%CI 13.07-23.32 vs 6.04-14.15; p = 0.014). Again, the statistical significance was not reached for progression-free survival (mPFS low NLR 8.3 months vs high NLR 5.8 months; 95%CI 4.81-11.78 vs 2.91-8.68; p = 0.214). Conclusions: Here, we demonstrated that the presence of indicators of systemic inflammation suchas high NLR and high PLR are associated with poor overall survival, but not withprogression-free survival in pre‐treated NSCLC patients who received nivolumabtreatment. The limitation of our study is the lack of a randomizedcontrol and small sample size. The main strength of our study is that it is real-worldeveryday clinical setting.

Introduction: HFNC is currently used in various settings and could provide optimal respiratory support for most bronchoscopic procedures including EBUS TBNA. Primary objective: to describe the efficacy, complication rate and risk factors for desaturation when using HFNC during EBUS TBNA. Methods: prospective, observational, single center study. All patients eligible for EBUS TBNA in deep sedation (RASS -4) during the 2 year study period were supported by HFNC (FiO2 0.5, flow rate 60L/min). Desaturation was defined as a persistent drop of SpO2 <88% requiring further intervention. Results: A total of 362 patients underwent EBUS TBNA, 41.4% female and 58.6% male, with a mean age of 63.5 years. HFNC provided effective respiratory support in 343 (95.7%) cases. Desaturation occurred in 5.3% (19/362) of cases requiring laryngeal mask insertion in 12 and endotracheal intubation in 7 patients. The average BMI in the whole cohort, stable (SG) and desaturation group (DG) were 27.0, 26.8 and 29.7 with 63.5%, 57.4% and 84.2% of patients having above normal BMI, respectively. There were 21.3% (73/343) obese patients in the SG, and 47.4% (9/19) in the DG (p=0.02). Respiratory insufficiency (RI) prior to EBUS was noted in 29.6% (107/362) of total cases, 28.6% (98/343) in the SD and 47.7% (9/19) in the DG (p=0.12). Serious adverse events included 1 cardiac arrest with successful resuscitation, transient hemodynamic instability in 7, vomiting in 3 and bronchospasm in 1 case. Unexpected ICU admission was required for 3 patients. Conclusion: HFNC provides adequate respiratory support during EBUS for most patients. However, desaturation was significantly more frequent among obese patients.

BACKGROUND: The most commonly used topical hemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on use of other agents such as tranexamic acid (TXA) for this purpose are limited. RESEARCH QUESTION: Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline? STUDY DESIGN AND METHODS: We conducted a cluster-randomized, double-blind, single-center trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to three applications of TXA (100 mg, 2 mL) or adrenaline (0.2 mg, 2 mL, 1:10000) after hemostasis failure after three applications of cold saline (4 degrees C, 5mL). Crossover was allowed (for up to three further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analog scale (VAS; 1 = very mild, 10 = severe). RESULTS: Atotal of 2,033 FBswere performed and 130 patients were randomized successfully to adrenaline (n = 65) or TXA (n = 65), whereas 12 patients had to be excluded for protocol violations (two patients from the adrenaline armand 10 patients from TXA arm). Bleeding was stopped in 83.1% of patients (54/65) in both groups (P = 1). The severity of bleeding and number of applications needed for bleeding control were similar in both groups (adrenaline: mean VAS score, 4.9 +/- 1.3 [n = 1.8 +/- 0.8]; TXA: mean VAS score, 5.3 +/- 1.4 [n = 1.8 +/- 0.8]). Both adrenaline and TXA were more successful in controlling moderate bleeding (86.7% and 88.7%, respectively) than severe bleeding (40% and 58.3%, respectively; P =.008 and P =.012, respectively) and required more applications for severe bleeding (3.0 +/- 0 and 2.4 +/- 0.5, respectively) than moderate bleeding (1.7 +/- 0.8 and 1.7 +/- 0.8, respectively) control (P =.006 and P =.002, respectively). We observed no drug-related adverse events in either group. INTERPRETATION: We found no significant difference between adrenaline and TXA for controlling noncatastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB.

Tumour development is affected by immune system. Inflammation markers can be used sometimes as prognostic factors. Numerous studies shown that high pretreatment neutrophil-to-lymphocyte ratio (NLR) levels are potential prognostic predictors for poor progression-free survival (PFS) and overall survival (OS) in NSCLC patients receiving immunotherapy.

Tracheal complications should be suspected in mechanically ventilated COVID-19 survivors with respiratory symptoms. Treatment requires a multimodal approach of interventional bronchoscopy and surgery with tight follow-up due to a high rate of restenosis. https://bit.ly/3iw05xQ.

The PACIFIC trial demonstrated significant improvement in progression-free survival and overall survival of patients with unresectable locally advanced NSCLC treated with durvalumab consolidation after concurrent chemoradiotherapy and changed the standard of care of this subset of NSCLC patients. We here present the real world data and outcomes of our patients diagnosed with unresectable locally advanced NSCLC and treated with concurrent or sequential chemoradiotherapy, followed by consolidation durvalumab.

Introduction: The most commonly used topical haemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on usage of other agents such as tranexamic acid (TXA) for this purpose are limited. Aims and objectives: to compare the efficacy of topical TXA versus adrenaline in controlling iatrogenic bleeding during FB. Methods: we conducted a cluster-randomized, double blind, single centre trial in a tertiary teaching hospital. Following haemostasis failure after 3 applications of cold saline (4°C, 5ml), patients were randomized to receive up to 3 applications of TXA (100mg, 2ml) or adrenaline (0.2mg, 2ml). If bleeding persisted, crossover was allowed (for up to 3 further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analogue scale (VAS; 1 - very mild, 10 - severe). Results: 2033 FB were performed during the study period with 563 bleeding episodes (mean VAS 2,82 ± 1,4). Bleeding was stopped with cold saline in 432 patients (76.7%). 130 patients were randomized to adrenaline (N=65) or TXA (N= 65). There were no differences in bleeding control rate between the groups - bleeding was stopped in 83.1% (54/65) and 83.1% (54/65) patients receiving adrenaline or TXA, respectively (p=1). The severity of bleeding and number of applications needed for bleeding control (N) were similar in both groups (adrenaline mean VAS = 4,94 ± 1,31, N=1.78 ± 0.79; TA mean VAS = 5,25 ± 1,44, N= 1.78 ± 0.79). Conclusion: The majority of bleeding during FB was successfully stopped with cold saline. TXA was not inferior to adrenaline in controlling moderately severe endobronchial bleeding.

Introduction: Postintubation tracheal stenosis (PITS) is a rare complication of mechanical ventilation (MV). Risk factors for PITS include prolonged MV, reintubation and poor endotracheal tube cuff management, all of which are common in severe COVID19 patients during pandemic surges. Aims and objectives: to describe the patient characteristics and outcomes of PITS after MV for COVID19. Methods: we conducted a retrospective review of all patients referred to our tertiary teaching hospital for endoscopic PITS treatment after COVID19 during 2021. Results: 60% of the 15 referred patients were female with a mean age of 60.1 years. Median duration of MV was 11.5 (8.5 – 16) days. 13.3% of patients were reintubated and 26.7% required tracheostomy during their ICU stay. 86.7% presented with stridor after a median of 32 (16.5-60) days after extubation with a further delay of 14 (2-42) days until the diagnosis of PITS. 73.3% had simple PITS with a mean diameter of 5.73±1.53 mm. 12 patients were successfully treated endoscopically with serial dilatation and electrocautery. Restenosis after treatment was observed in 66.7% of patients after a median of 30 (22.5-35) days. 5 patients required surgery while 2 patients required further endoscopic dilatation after surgery. Interestingly, 13 of the 15 patients were referred from a single tertiary hospital, after treatment in the same ICU. Conclusions: We observed an increase in referrals for PITS treatment during the study period with a cluster of patients from a single ICU. The high restenosis rate emphasizes the importance of multidisciplinary management as well as the prevention of PITS with high quality ICU care during the COVID19 pandemic.

Anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers (approximately 5%) what gives patients better survival outcomes. We analyzed the data of the patients diagnosed with advanced stage ALK positive NSCLC in University hospital center Zagreb, Department for pulmonary diseases from January 2018 until December 2020. In observed period of time 64 patients were treated with ALK TKIs. 29 patients were treated with crizotinib in the first line and 27 of them progressed at the time of data cut off and 25 received alectinib in the second line, while one patient was treated with brigatinib. 35 patients were treated with alectinib in the first line. In the third line setting 10 patients were treated with brigatinib or lorlatinib. ALK TKIs were administered in the first line setting in 44 patients, in the second line setting in 14 patients and some patients were treated in the third, fourth and even fifth line (2, 3 and 1, respectively). There were 35 (55%) females with median age of 65 years (36-82). Almost half of them (43%) were current or ex-smokers with median pack/years 26.9 (2-75). Diagnosis was established by cytology specimens in 18 (27%) and by histology specimens in 46 (73%) patients. We observed median overall survival for all treated patients (mOS) of 47 months (95%CI 21.6-72.3), while mOS for patients treated with alectinib in the first line was not reached. Median progression-free survival (mPFS) was 12 months (95%CI 6,2 -14,7), but divided by TKIs - for crizotinib was 8 months (95% CI 5,1 – 10,8) and for alectinib it was not reached. mPFS2 for alectinib is 12 months (95%CI 2,3 – 21,6). We present real-life data of survival outcomes associated with sequencing of different ALK TKIs. Our data suggest that treatment with alectinib in the first line gives better survival benefit than earlier generation ALK TKIs.

Introduction: Only 5% of lung adenocarcinomas have the anaplastic lymphoma kinase (ALK) gene rearranged. It gives patients the opportunity to be treated with targeted ALK tyrosine kinase inhibitors (ALK TKI). Methods: We analyzed data of the patients diagnosed with advanced stage ALK positive lung adenocarcinoma in University hospital center Zagreb, Department for pulmonary diseases from January 2018 until December 2020. Results: During this period 64 patients were treated with ALK TKIs, 29 with crizotinib and 35 with alectinib. Out of 29 patients that were treated with crizotinib in the first line, 27 progressed at the time of data cut off and 25 received alectinib in the second line, while one patient was treated with brigatinib. In the third line setting 10 patients were treated with brigatinib or lorlatinib. There were 35 (55%) females with median age 65 years (36-82). Almost half of them (43%) had smoking history with median pack/years 26.9 (2-75). We observed median overall survival (mOS) of 47 months (95%CI 21.6-72.3), while mOS for patients treated with alectinib in the first line was not reached. Median progression-free survival (mPFS) was 12 months (95%CI 6,2 -14,7), but for crizotinib was 8 months (95% CI 5,1 – 10,8) and for alectinib it was not reached. mPFS2 for alectinib is 12 months (95%CI 2,3 – 21,6). Conclusion: We present real-life data on outcomes associated with sequencing of different ALK TKIs. Our data suggest that treatment with alectinib in the first line gives better survival benefit compared to first generation TKIs. To date, no evidence was found directly comparing different ALK inhibitor sequences so real life data are very important in future treatment strategies.

First-line pembrolizumab monotherapy in patients with PDL1-high non-small cell lung cancer significantly improves progression-free survival and overall survival continuing to demonstrate benefit with prolonged follow-up. The aim of present study is to compare outcomes in real-world oncology practice with pivotal clinical trials.

Lung cancer death rate in women rose in the past years surpassing breast cancer as the main cause of cancer mortality. The rise in lung cancer mortality in women appears to corelate with the increased prevalence of smoking. Adenocarcinoma has become the most frequent histologic subtype in both genders, and women present with adenocarcinoma in a higher proportion than men do. Medical records of the patients diagnosed with lung cancer in Clinical hospital center Zagreb, Department for respiratory diseases Jordanovac during the year 2012 were retrospectively collected and reviewed. Baseline data were reported using descriptive statistics. Survival analysis was measured and analyzed using the Kaplan-Meier and log-rank test. During the year 2012 there were 661 patients diagnosed with lung cancer in our Department. 482 (73%) were men and 179 (27%) were women. Median age at diagnosis was 64 (37-90). Total lifetime amount smoked varied from 2 to 200 pack/years in the smokers, with median 41 pack/years. The most predominant histological type was adenocarcinoma (287 patients, 43%), followed by squamous cell carcinoma (185; 28%) and microcellular carcinoma (79; 12%). Women had proportionally more adenocarcinoma and less squamous cell carcinoma than men. Cumulative exposure of smoking (as measured by pack-years of cigarettes) is significantly different with 33,6% of men smoking more than 50 pack years compared to 11,7% of women (p < 0.01). No significant difference in stage was observed across genders (p = 0.40). There were no significant differences in treatment between genders. Median overall survival (mOS) for all diagnosed lung cancer patients was 9 months. 1-year survival for all lung cancer patients is 39%, and 5-year survival is 8.1%. Female patients had significantly better survival rates. 1-year survival for female patients is 46% versus male patients 37%. 5-year survival rate for female patients is 11% versus male patients 7%. Male gender has been reported as a significant independent negative prognostic factor for patients with lung cancer in previous studies. Our results are similar to these findings. Over the last 20 years there were changes in the epidemiology of lung cancer between men and women. Characteristics of our patient population reflect the current trends of lung cancer epidemiology. Female patients smoke less but seem more susceptible to develop lung cancer. Although adenocarcinoma is the most common subtype in both genders, women have proportionally more adenocarcinomas than men do. Women have better survival than men.