Thoracic SMARCA4-deficient undifferentiated tumor: a systematic review and meta-analysis of individual patient data with cross-cohort survival comparison

Background: -UT) is a rare, highly virulent neoplasm lacking a standardized therapeutic protocol. Because current evidence is scarce, systemic management guidelines are not well-defined. We aimed to address this lack of data by synthesizing individual patient-level data from case reports and retrospective series. Our goal was to characterize treatment patterns and survival, focusing on combination strategies using immune checkpoint inhibitors (ICIs). Methods: A systematic literature search was performed in PubMed, Embase, and Web of Science from database inception to November 30, 2024, in accordance with PRISMA guidelines. Individual patient data were extracted from eligible published case reports and case series and pooled for unified survival analysis. Aggregated survival data from retrospective cohort studies were summarized for cross-study comparison. Overall survival (OS) was analyzed using the Kaplan-Meier method, and treatment-specific outcomes were visualized using swimmer plots and forest plots. Results: -UT were included, consisting of 26 patients with individual-level data and 8 retrospective cohort studies. Patients were mostly male heavy smokers, and most cohort studies consisted of advanced-stage disease. In the pooled individual patient dataset, 46.2% of patients received first-line chemotherapy plus immunotherapy (Chemo-IO). The median OS (mOS) of pooled cases was 15.0 months, exceeding that reported in most retrospective cohorts treated predominantly with chemotherapy or immunotherapy monotherapy (mOS range, 4.0-7.7 months). Long-term survival was observed almost exclusively in patients receiving Chemo-IO or multimodal treatment. Clinical benefit from Chemo-IO was also observed in patients with negative PD-L1 expression. Conclusions: -UT, regardless of PD-L1 expression. Data support using immunotherapy-based regimens early as a first-line treatment for this aggressive disease. These real-world findings offer guidance for clinical decision-making while prospective trials are unavailable.