A binary survival model, incorporating Fibulin-3, predicts survival in pleural mesothelioma

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Introduction: The Brims model classifies patients with pleural mesothelioma into 4 prognostic groups. However at diagnosis, clinicians and patients face a binary choice between immediate treatment or ‘watch-and-wait’, with the latter being high-risk if patients rapidly progress. We devised a new binary model aiming for similar performance to Brims, using the previously published DIAPHRAGM study dataset (Tsim et al, JTO 2021), including novel biomarker data. Methods: A 3-group model for 1-yr survival was derived from multivariable Cox regression hazard ratios in the DIAPHRAGM dataset (n=100). Performance was measured by C-statistic (C), compared to Brims and then validated externally in the Scottish national MDT dataset (n=203). Fibulin-3 (F3) was then used to stratify intermediate-risk DIAPHRAGM cases to create the binary Glasgow Mesothelioma Score (GMS). Results: 6 independent features contributed to the 3-group DIAPHRAGM model (Fig 1a), which delivered superior performance to Brims (C=0.72 v 0.66). This model retained performance in the validation cohort (C=0.60, 1-yr survival 38%, 56%, 75% in high/intermediate/low-risk; Fig1b). Stratification of intermediate-risk cases by F3 (≥16 µg/mL), creating GMS, significantly improved performance (C=0.73, 1-yr survival 70% v 9% in high/low risk, see Fig 1c-d). Conclusion: GMS combines F3 with an externally validated 3-group model to create a powerful binary classifier. This may be useful in identifying patients unsuitable for ‘watch-and-wait’ due to rapid progression risk. erj;66/suppl_69/OA5514/F1 F1 F1

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