Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in malignant pleural mesothelioma.

Abstract

7086 Background: Radiological response evaluation is notoriously difficult in patients with malignant pleural mesothelioma, an asbestos-related malignancy. Soluble mesothelin (SM), megakaryocyte potentiating factor (MPF), and osteopontin (OPN) are blood biomarkers of mesothelioma. This study evaluates their use as markers of response to therapy and outcome. Methods: 62 patients with malignant pleural mesothelioma were surveilled in a Belgian observational multicenter study. Blood samples and CTs were collected at diagnosis and, when possible, during and after therapy, until disease progression or death. SM and MPF levels were measured in serum with the Mesomark ELISA and the non-commercial Human MPF ELISA, respectively. OPN levels were measured in plasma with the Human Osteopontin ELISA. For each patient, the best overall radiological response was compared with the change in serum SM, MPF and plasma OPN levels across the corresponding time points. Survival analysis was performed with Cox proportional hazard regression and log-rank statistics. Results: In five patients who underwent extrapleural pneumonectomy, SM and MPF markedly decreased after surgery, whereas OPN showed a median increase. Of the 57 patients who received chemotherapy, 27 (47%) had radiological stable disease (SD), 14 (25%) partial response (PR), and 16 (28%) progressive disease (PD). In patients with SD, biomarker levels did not change significantly (SM and MPF), or decreased (OPN). For PR and PD, biomarker levels typically decreased and increased, respectively. A change ≥15% in all three biomarkers significantly correlated with patient response, whereas SM and MPF appeared more accurate than OPN. Low baseline OPN levels were independently associated with favorable overall and progression free survival. Neither SM nor MPF were informative for patient outcome. Conclusions: Relative changes in SM, MPF and OPN all three correlated with disease course, whereas SM and MPF appeared most suitable for monitoring of patients with mesothelioma. Baseline OPN levels were an independent negative predictor of survival. Further validation of these promising results remains mandatory.