Phase 3 trials of neoadjuvant immunotherapy-based regimens have shown promising outcomes in patients with resectable non-small cell lung cancer (NSCLC). However, real-world data on treatment regimens with combined chemoimmunotherapy, patient profiles, and clinical outcomes in those patients are limited. This dual-center registry-based study describes clinical patterns and outcomes of using neoadjuvant platinum-based chemoimmunotherapy in patients with resectable NSCLC. The main objective was to evaluate the proportion of patients receiving local therapy after chemoimmunotherapy. Further objectives include pathological outcome, disease-free survival (DFS), and overall survival (OS). Histological samples underwent next-generation sequencing (NGS). Seventy-two patients (median age 64.5 years (interquartile range (IQR), 59-69); 40.3 % women) were included. Prior to initiation of therapy, NGS was available in 90.3 %. Median follow-up time from date of diagnosis was 374 days (IQR, 241-605). After neoadjuvant therapy, 46 patients underwent surgery and 23 radiotherapy, resulting in 69 patients receiving local therapy. Out of 46 patients who underwent surgery, 22 had pathological complete remission (PR), 11 major PR, and 12 minor PR. DFS (95 % confidence interval (CI)) in 43 (out of 46) surgical patients with R0 resection was 98 % (93-100), 98 % (93-100) and 81 % (57-100) after 180, 360 and 720 days, respectively. OS (95 % CI) was 97 % (94-100), 90 % (82-99) and 90 % (82-99), after 180, 360 and 720 days, respectively. Following neoadjuvant chemoimmunotherapy, the majority of resectable early-stage NSCLC patients could undergo local therapy in routine clinical practice. This was associated with favorable DFS and OS.

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.

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/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: Disease recurrence is common after surgery for pleural mesothelioma (PM), and the evidence guiding post-recurrence management remains limited. Methods: We conducted a retrospective, single-center cohort study including patients with PM treated within a curative-intent multimodality treatment pathway including surgery aiming for a macroscopic complete resection when feasible between 2001 and 2024. Post-recurrence treatments were categorized as best supportive care only (BSC), systemic therapy alone, or local with or without systemic therapy. Survival and disease-free outcomes were analyzed in relation to treatment patterns and clinical prognostic factors. Results: Among 67 patients with a median follow-up time of 107 months from surgery, 58 (86.6%) developed disease recurrence. At first recurrence, 21 patients (36%) received local with or without systemic therapy, 26 (45%) systemic therapy alone, and 11 (19%) BSC. The median post-recurrence survival was 21.7 months for patients receiving local with or without systemic therapy, 10.8 months for systemic therapy alone, and 1.6 months for BSC. Lung-sparing surgery and a disease-free interval of at least 12 months were associated with improved post-recurrence survival and post-recurrence progression-free survival. Conclusions: In this real-world cohort of patients with PM and extended follow-up, active post-recurrence treatment was associated with longer post-recurrence survival in selected patients. However, conclusions regarding their comparative effectiveness are limited by the retrospective design, incomplete recurrence-related data, and patient selection at recurrence.

Background: Disease recurrence is common after surgery for pleural mesothelioma (PM), and evidence guiding post-recurrence management remains limited. Methods: We conducted a retrospective, single-center cohort study including patients with PM treated within a curative-intent multimodality treatment pathway including surgery aiming for macroscopic complete resection when feasible between 2001 and 2024. Post-recurrence treatments were categorized as best supportive care only (BSC), systemic therapy alone, or local with or without systemic therapy. Survival and disease-free outcomes were analyzed in relation to treatment patterns and clinical prognostic factors. Results: Among 67 patients with a median follow-up time of 107 months from surgery, 58 (86.6%) developed disease recurrence. At first recurrence, 21 patients (36%) received local with or without systemic therapy, 26 (45%) systemic therapy alone, and 11 (19%) BSC. Median post-recurrence survival was 21.7 months for patients receiving local with or without systemic therapy, 10.8 months for systemic therapy alone, and 1.6 months for BSC. Lung-sparing surgery and a disease-free interval of at least 12 months were associated with improved post-recurrence survival and post-recurrence progression-free survival. Conclusion: In this real-world cohort of patients with PM with extended follow-up, active post-recurrence treatment was associated with longer post-recurrence survival in selected patients. However, conclusions regarding comparative effectiveness are limited by the retrospective design, incomplete recurrence-related data, and patient selection at recurrence.