# The Mesothelioma Systemic Inflammation Score Is Independently Associated with Overall Survival and Predicts Benefit of Multimodality Treatment in Pleural Mesothelioma

## TL;DR

A new inflammation-based score helps predict survival and treatment benefits in pleural mesothelioma patients.

## Contribution

The Mesothelioma Systemic Inflammation Score (MSIS) is introduced as a novel prognostic and predictive tool for treatment outcomes.

## Key findings

- MSIS independently predicts overall survival in pleural mesothelioma patients.
- Multimodality treatment benefits are limited to patients with low MSIS.
- MSIS accurately stratifies patient survival outcomes across two independent cohorts.

## Abstract

Few malignancies generate as many controversies about clinical management as pleural mesothelioma. The merits of multimodality treatment protocols have been continuously discussed, often with limited evidence from prospective trials. Given that the first randomized prospective studies investigating the role of surgery in mesothelioma produced debatable results, it may be too soon to retire the concept of multimodality treatment protocols including surgery for selected candidates. Accurate prognostication could improve treatment allocation, offering multimodality therapy pathways or sparing patients from aggressive and potentially morbid treatment strategies. The aim of our study was to validate the prognostic and predictive power of a novel inflammation-based score—the Mesothelioma Systemic Inflammation Score (MSIS)—in a large cohort of pleural mesothelioma patients treated in a high-volume institution. The prognostic impact of MSIS was further validated in an independent cohort. The pretreatment Mesothelioma Systemic Inflammation Score was found to predict treatment benefits of surgery within multimodality treatment by stratifying patient groups with significant survival differences.

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.