The use of a next-generation sequencing-derived machine-learning risk-prediction model (OncoCast-MPM) for malignant pleural mesothelioma: a retrospective study.BACKGROUND
 Therefore, we aimed to develop and validate a machine-learning tool-known as OncoCast-MPM-that could create a model for patient prognosis.


 Using OncoCast-MPM, an open-source, web-accessible, machine-learning risk-prediction model, we integrated available data to create risk scores that stratified patients into low-risk and high-risk groups.  The median overall survival was higher in the low-risk group than in the high-risk group as determined by OncoCast-MPM (30·8 months [95% CI 22·7-36·2] vs 13·9 months [10·7-18·0]; hazard ratio [HR] 3·0 [95% CI 2·0-4·5]; p<0·0001).  OncoCast-MPM was validated against the TCGA cohort, which consisted of 74 patients.  Although stage-based risk stratification was unable to differentiate survival among risk groups at 3 years in the MSK-IMPACT cohort (31% for early-stage disease vs 30% for advanced-stage disease; p=0·90), the OncoCast-MPM-derived 3-year survival was significantly higher in the low-risk group than in the high-risk group (40% vs 7%; p=0·0052).


 OncoCast-MPM generated accurate, individual patient-level risk assessment scores.  After prospective validation with the TCGA cohort, OncoCast-MPM might offer new opportunities for enhanced risk stratification of patients with malignant pleural mesothelioma in clinical trials and drug development.



OncoCast-MPM
We did a retrospective study looking at malignant pleural mesothelioma tumours using next-generation sequencing from the Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT).  We collected clinical, pathological, and routine next-generation sequencing data from consecutive patients with malignant pleural mesothelioma treated at the Memorial Sloan Kettering Cancer Center (New York, NY, USA), as well as the MSK-IMPACT data.  Together, these data comprised the MSK-IMPACT cohort.  Risk stratification of the MSK-IMPACT cohort was then validated using publicly available malignant pleural mesothelioma data from The Cancer Genome Atlas (ie, the TCGA cohort).


 Between Feb 15, 2014, and Jan 28, 2019, we collected MSK-IMPACT data from the tumour tissue of 194 patients in the MSK-IMPACT cohort.  Although stage-based risk stratification was unable to differentiate survival among risk groups at 3 years in the MSK-IMPACT cohort (31% for early-stage disease vs 30% for advanced-stage disease; p=0·90), the OncoCast-MPM-derived 3-year survival was significantly higher in the low-risk group than in the high-risk group (40% vs 7%; p=0·0052).



MSK-IMPACT