Objectives: The ratio of positive and resected lymph nodes (LN ratio) has been shown to be prognostic in non-small cell lung cancer (NSCLC). Contrary to the LN ratio, calculating the LN log-odds ratio (LN-LOR) additionally considers the total number of resected lymph nodes. We aim to evaluate LN-LOR between positive and resected lymph nodes as a prognostic factor in operable NSCLC. Methods: Patients with NSCLC who underwent curative intent lobectomy treated at two high-volume centers were retrospectively studied. LN-LOR was dichotomized according to impact on OS and further combined with N descriptors and correlated with clinical variables and survival. Results: 944 patients were included. Cut-off analysis revealed that an LN-LOR of −0.34 significantly discriminated patients according to OS (p < 0.001, chi-squared test 41.26). When combined with N1 and N2 descriptors, LN-LOR low risk (median OS not reached and 83 months) and LN-LOR high-risk patients (median OS 50 and 59 months) had similar survival irrespective of the anatomical location of the positive lymph nodes. Multivariable Cox regression analysis revealed that age (HR 1.02, 95% CI 1.001–1.032), sex (male, HR 1.65, 95% CI 1.25–2.19), histological subtype (HR 2.11, 95% CI 1.35–3.29), pathological stage (HR 1.23, 95% CI 1.01–1.45) and LN-LOR risk groups (low risk, HR 0.48, 95% CI 0.32–0.72) were independent prognostic factors for OS. Conclusions: This retrospective two-center analysis shows that LN-LOR is significantly associated with OS in resectable NSCLC and might better reflect the biological behavior of the disease, regardless of anatomical lymph node locations. This finding may additionally support the value of extensive LN dissection.

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

Background: Few malignancies provoke as many controversies about treatment as pleural mesothelioma. There is limited experience with novel radiotherapy techniques worldwide in adjuvant and particularly in neoadjuvant settings within multimodality treatment. The objective of the current study was to investigate the long‐term outcome of neoadjuvant and adjuvant pleural intensity‐modulated radiotherapy (IMRT) combined with macroscopic complete resection with or without chemotherapy.Methods: We retrospectively analyzed a consecutive cohort of 59 patients who were diagnosed with pleural mesothelioma and underwent multimodality treatment including macroscopic complete resection and neoadjuvant or adjuvant IMRT between 2005 and 2019 at the Department of Thoracic Surgery, Medical University of Vienna, Austria.Results: In total, 59 patients (median age 59 years; IQR 54–66, male, n = 48; 81%) were included. Forty‐seven patients underwent trimodality treatment consisting of induction chemotherapy, extrapleural pneumonectomy, and adjuvant IMRT. Novel neoadjuvant IMRT with (n = 9) or without (n = 3) chemotherapy followed by extrapleural pneumonectomy was performed in 12 patients. Median overall survival (OS) of all patients was 23.2 months (95% CI; 18.1–28.2) and 3‐ and 5‐year survival rates were 33% and 28%, respectively. Survival was comparable between therapies including neoadjuvant versus adjuvant IMRT (median OS 17.5 vs. 24.0 months, p = 0.39).Conclusions: Neoadjuvant pleural IMRT has been investigated as a novel treatment option for highly selected cases in pleural mesothelioma. Neoadjuvant IMRT was effective and safe in patients treated in a high‐volume institution but showed no relevant survival benefit compared to adjuvant IMRT within multimodality treatment.

Background/Objectives: Malignant pleural mesothelioma (MPM) remains challenging to treat, with a poor prognosis. As controversy about clinical management continues, predictive biomarkers for patient selection to indicate the benefit of treatment modalities are urgently needed. Methods: In a retrospective analysis of 195 patients between 1994 and 2020 at the Department of Thoracic Surgery, Medical University of Vienna, Austria, the Mesothelioma Systemic Inflammation Score (MSIS)—consisting of pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), and fibrinogen—was tested for its prognostic and predictive significance. The prognostic impact of MSIS was subsequently validated in an independent cohort of 80 patients treated at the Department of Thoracic Surgery, Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, Vienna, Austria. Results: Median overall survival (OS) was 14 months for the entire cohort (95% CI: 11.4–16.6). Patients undergoing multimodality treatment including macroscopic complete resection had a longer OS (22.3 months, 95% CI: 18.6–26.0; p < 0.001). In multivariable analysis, MSIS (p < 0.001), disease stage (p = 0.001), and the type of treatment (p = 0.004) were confirmed as independent predictors for OS. Higher MSIS was associated with shorter OS (p < 0.001). Significant survival benefit of multimodality regimens including surgery was limited to patients with low MSIS. Among patients with low (≤ 2) MSIS, multimodality therapy was associated with significantly prolonged OS when compared with chemo- and/or radiotherapy alone (25.8 months [95% CI: 16.4–35.3] vs. 14.4 months [95% CI: 10.4–18.4], p < 0.001). In contrast, among patients with elevated MSIS, no survival benefit was achieved by surgery over conservative treatment (11.8 months [95% CI: 8.3–15.3] vs. 8.2 months [95% CI: 5.2–11.3], p = 0.233). The ability of MSIS to predict survival was equivalent between the baseline and the independent validation cohort (p < 0.001). Conclusions: The Mesothelioma Systemic Inflammation Score was found to be an independent prognostic score in pleural mesothelioma, predicting benefit from macroscopic complete resection as part of multimodality treatment in distinct patients.

Background and Objective: Due to the increasing use of imaging and lung cancer screening programs, the rate of detected pulmonary nodules has steadily increased over the past decade. Overall, the diagnosis and management of pulmonary nodules remain challenging. Moreover, no specific guidelines exist for the management of pulmonary nodules in patients with a history of previous malignancy. This study reflects the current management in a real-world setting in a specialized European center. Methods: In this retrospective single-center study, patients with a pulmonary nodule <3 cm referred to the Division of Pulmonology or the Department of Thoracic Surgery at the Medical University of Vienna, Austria, from November 2022 to July 2024, were analyzed. A subgroup analysis of patients with a history of previous malignancy was performed and compared to patients without previous malignancies. Results: In total, 356 patients (48.5% male, median age 67 years [IQR 61–74], 53.7% with a history of previous cancer) with a pulmonary nodule (mean size of 14.8 mm) were enrolled. Bronchoscopy, computed tomography (CT)-guided biopsy, or surgery was performed in 13.2%, 7.3%, and 65.2% of the cases, respectively. The overall malignancy rate was 70.5%. Pulmonary nodules in patients with a prior malignancy were significantly larger (p < 0.001), showed a progression in size (p < 0.001), and were found to be malignant more frequently when compared to patients without previous cancer (p = 0.032). Conclusions: As most patients referred to a specialized center represent a selected group of high-risk patients, the majority of pulmonary nodules were found to be malignant. In patients with a history of previous malignancy, tissue sampling is warranted as the rate of malignancy is high.

Reactive oxygen species (ROS)-induced aberrant oncogenic signaling has been proposed to mediate the progression and development of pleural mesothelioma (PM). Here we demonstrate how ROS initiates oncogenic signaling especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X) and xanthine oxidase (XO)-generated ROS exposure led to increased migration and more elongated cell shape in mesothelial and PM cells in live cell videomicroscopy analyses. These effects were associated with enhanced phosphorylation of ERK, AKT and YB-1, alongside elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. Pharmacological inhibition of AKT (ipatasertib), MEK (trametinib) or RSK (BI-D1870) resulted in reversal of ROS-induced effects, with the strongest effects observed upon inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune evasive effects in PM.