The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne^®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne^® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne^®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice.

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.

Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence of EGFR mutations was 11% (145 out of 1267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4–24.9) and 14.2 months (95% CI: 7.4–20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, the EGFR common mutation subtype (HR = 3.71 95%CI: 1.23–11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18–21. Conclusions: The results underscore the prognostic role of distinct EGFR genotypes and the urgency of determining the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mutations and the resulting need for further research to investigate alternative treatment options.

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.