Summary: Background: Lung cancer is a major health burden in Austria; however, limited real-world data exist on the diagnostic and treatment reality of lung cancer patients in Austria. The collection of high-quality data in a clinical setting is needed to gain insights into the real-world diagnostic and therapeutic management of lung cancer patients. Methods: The Karl Landsteiner Institute for Lung Research and Pulmonary Oncology implemented the Landsteiner lung cancer research platform (LALUCA), recruiting unselected lung cancer patients from two high volume centers in Vienna. This article describes the objectives, design, methodology of the registry and the process of implementation. Results: A multidisciplinary team of lung cancer specialists created a custom designed variable catalogue for the LALUCA platform consisting of 17 categories with 180 variables. Detailed information on clinical characteristics, diagnostic interventions, molecular pathology as well as curative and palliative treatment modalities are collected. During an implementation phase in 2020, the platform was optimized using the data of 50 patients. Since then a total of 1200 patients have been enrolled. Recruitment for the registry is ongoing with a recruitment rate of approximately 400 patients per year. Conclusion: The LALUCA registry is a web-based platform for the collection of real-world clinical data of lung cancer patients. Combining a large number of patients with a focus on gathering comprehensive data on diagnosis and treatment, the LALUCA registry provides a tool for investigation, evaluation, and improvement of the clinical management, survival and quality of care of Austrian lung cancer patients.

Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1–25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13–0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64–15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1–25.4) vs. 31.3 (17.4–95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.

Background: Impairment in autonomic activity is a prognostic marker in patients with heart failure (HF), and its involvement has been suggested in cardiovascular complications of obstructive sleep apnea syndrome (OSAS) and Cheyne–Stokes respiration (CSR). This prospective observational study aims to investigate the implications of sleep-disordered breathing (SDB) on hemodynamic regulation and autonomic activity in chronic HF patients. Methods: Chronic HF patients, providing confirmation of reduced ejection fraction (≤35%), underwent polysomnography, real-time hemodynamic, heart rate variability (HRV), and baroreceptor reflex sensitivity (BRS) assessments using the Task Force Monitor. BRS was assessed using the sequencing method during resting conditions and stress testing. Results: Our study population (n = 58) was predominantly male (41 vs. 17), with a median age of 61 (±11) yrs and a median BMI of 30 (±5) kg/m². Patients diagnosed with CSR were 13.8% (8/58) and 50.0% (29/58) with OSAS. No differences in the real-time assessment of hemodynamic regulation, heart rate variability, or baroreceptor reflex function were found between patients with OSAS, CSR, and patients without SDB. A subgroup analysis of BRS and HRV in patients with severe SDB (AHI > 30/h) and without SDB (AHI < 5) revealed numerically reduced BRS and increased LF/HF-RRI values under resting conditions, as well as during mental testing in patients with severe SDB. Patients with moderate-to-severe SDB had a shorter overall survival, which was, however, dependent upon age. Conclusions: Chronic HF patients with severe SDB may exhibit lower baroreceptor function and impaired cardiovascular autonomic function in comparison with HF patients without SDB.

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) often shows incomplete responses and progression despite tyrosine kinase inhibitor (TKI) therapy. Preliminary data suggest that combining brigatinib, an ALK-selective TKI, with surgery or radiotherapy may improve outcomes. We retrospectively analyzed patients with advanced ALK-positive NSCLC who received brigatinib as first-line treatment combined with local therapy to assess safety and efficacy of this approach in a real-world setting. Among 9 patients, 6 (67%) had stage III and 3 (33%) had stage IV adenocarcinoma. Five patients received surgery, 3 received radiotherapy, and 1 received both. Brigatinib-related adverse events (AEs) occurred in 78% of patients, primarily mild (grade ≤ 2). Severe AEs (grade ≥ 3) were seen in 22% of patients and included dyspnea and hypertension. Brigatinib was discontinued in 22% of patients due to toxicity. Local therapy-related AEs were mostly grade 1. The objective response rate was 89%, with 2 complete and 6 partial responses. At data cutoff, brigatinib was ongoing in 55% of patients, with a median treatment duration of 14 months and a 2-year progression-free survival rate of 100%. Combining brigatinib with local therapy appears safe and potentially more effective for advanced ALK-positive NSCLC. Further studies are warranted.

Background: Adenosquamous carcinoma of the lung (ASC) is a rare non-small-cell lung cancer (NSCLC) subtype combining components of squamous cell carcinoma (SCC) and adenocarcinoma (AC). Data on ASC, particularly in Caucasian populations, are limited. Methods: We reviewed clinicopathological and radiological characteristics of ASC patients diagnosed between 1996 and 2023. Patients were classified into AC-predominant ASC (AC-ASC) and SCC-predominant ASC (SCC-ASC) groups for analysis. Results: Among the 66 patients included, the median overall survival was 41.7 (95% CI, 25.0–54.4), while it was 48.1 (95% CI, 27.3–88.0) in patients treated with curative surgery (n = 44) and 15.3 (95% CI, 6.5–42.6) months for palliative patients (n = 22). The five-year survival rates were 39% and 26%, respectively. Recurrence occurred in 43% of stage I patients and was associated with worse survival (HR 3.303 (95% CI, 1.10–9.89) p = 0.033). AC-ASCs (n = 17) more frequently showed air-bronchogram (p = 0.002) and pleural effusions (p = 0.054) compared to SCC-ASCs (n = 26). SCC-ASCs exhibited more vascular invasion (p = 0.006) and PD-L1 values between 1 and 49% (TPS) (p = 0.032). The subtype did not influence survival. EGFR and ALK alterations were found in 17% and 2% of patients, respectively. Conclusions: Despite early-stage disease, ASC patients had a high recurrence rate, associated with worse survival. Clinicopathologic differences between AC-ASCs and SCC-ASCs did not influence survival.

Background Extensive-stage small cell lung cancer (ES-SCLC) has a dismal prognosis as patients progress within months after first-line systemic treatment. Topotecan is currently the approved second-line treatment in Europe. However, due to its limited efficacy, various treatment strategies are being employed. This study aimed to depict the therapeutic landscape of second-line treatment in ES-SCLC and to evaluate survival outcomes in a real-world setting. Methods Data from the Austrian LALUCA registry, a prospective, multicenter clinical lung cancer registry, were reviewed for all patients diagnosed with ES-SCLC between November 2020 and October 2025. Clinical and treatment characteristics were assessed with special emphasis to second-line treatment. The primary outcomes were overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT). Results Among 231 patients with histologically confirmed ES-SCLC included in this study, 75 patients (32.5%) received second-line therapy. The main reason for no second-line treatment at data cut-off was death in 40.7%, followed by ongoing first-line treatment in 22.8% and switch to best supportive care only in 15.2%. Second-line treatment consisted of anthracycline-based treatment regimen in 57.3%, topotecan in 26.7% and re-challenge of platinum-based chemo- or chemoimmunotherapy in 16.0% of patients. The median duration of second-line treatment was 2 months (range: 0.03-8.2) with a median PFS of 4.7 months (95% CI; 3.9, 5.8), and median OS of 7.1 months (95% CI; 5.1, 9.3). The median TTNT between first- and second-line treatment was 0.97 months (range: 0.10 – 36.5). The main reasons for treatment discontinuation were disease progression in 29.3%, followed by completed regimen in 25.3% and death in 13.3%. Conclusion This real-world analysis shows poor outcomes in patients with progressing ES-SCLC, reflected by both short median PFS and duration of second-line treatment, along with high rates of treatment discontinuation, highlighting the urgent need for more effective and tolerable treatment options.