Plasma Biomarker Enrichment of Clinical Prognostic Indices in Malignant Pleural Mesothelioma
Journal of Thoracic Oncology 2016 February 19 [Epub ahead of print] [Link]
Pass HI, Goparaju C, Espin-Garcia O, Donington J, Carbone M, Patel D, Chen Z, Feld R, Cho J, Gadgeel S, Wozniak A, Chachoua A, Leighl N, Tsao MS, de Perrot M, Xu W, Liu G.
Prognostic models for pleural mesothelioma (MPM) are needed to prevent potentially futile outcomes. We combined MPM plasma biomarkers with validated clinical prognostic indices to determine whether stratification of risk for death in 194 MPM patients improved.
Patients and Methods
Individuals were recruited from three different centers: a discovery cohort (83 MPM) created by combining patients from two US centers and a separate, independent cohort from Canada (111 MPM). Univariable/multivariable analyses were performed on the initial discovery and independent cohorts separately. In multivariable analyses, prognostic factors were adjusted for the Mesothelioma EORTC Prognostic Index (PI). The prognostic significance of adding plasma biomarker data to the PI was determined using the likelihood ratio test, comparing models with and without the addition of biomarker to the clinical PI. The predictive ability of the biomarker was then assessed formally using Harrell’s c-index by applying the fitted model variables of the discovery cohort to the second, independent cohort, including and not including the biomarker with the PI.
Higher levels of osteopontin and mesothelin were individually associated with worse prognosis after adjusting for the PI. In the independent cohort, incorporating either plasma osteopontin or mesothelin into the baseline predictive PI model substantively and statistically significantly improved Harrell’s c-statistic. In the final prognostic model, log-osteopontin, EORTC CPI, and hemoglobin remained as independently significant predictors, and the entire prognostic model improved the optimism-corrected Harrell’s c-index significantly from 0.718 (0.67-0.77) to 0.801 (0.77-0.84).
These data suggest a possible role for preoperative plasma biomarkers to improve prognostic capability of the MPM EORTC PI.