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

Our plain-English summary of Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma, by K. Hollevoet, K. Nackaerts, R. Gosselin, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: K. Hollevoet, K. Nackaerts, R. Gosselin, W. De Wever, L. Bosquée, P. De Vuyst, P. Germonpré, E. Kellen, C. Legrand, Y. Kishi, J.R. Delanghe, J.P. van Meerbeeck
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(11):1930-7
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: 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: Sixty-two patients with malignant pleural mesothelioma were included in an observational multicenter study. Blood samples and matched computed tomography scans were collected at diagnosis and, when possible, during and after therapy. For each patient, the best overall radiological response was compared with the changes in serum SM, MPF, and plasma OPN levels across corresponding time points.

Results: In five patients, blood sampling was done shortly before and after extrapleural pneumonectomy. SM and MPF levels markedly decreased after surgery, whereas OPN levels showed a median increase. Fifty-seven patients were surveilled during (and after) chemotherapy, of whom 27 (47%) had stable disease, 14 (25%) partial response, and 16 (28%) progressive disease. In patients with stable disease, SM and MPF levels did not change significantly across the corresponding time points, whereas OPN levels significantly decreased. In those with partial response, SM and MPF levels significantly decreased, whereas OPN levels showed no significant change. In patients with progressive disease, all three biomarker levels significantly increased. Patient responses correlated with a 15% change in all three biomarkers, although SM and MPF appeared more accurate than OPN. Low baseline OPN levels were independently associated with favorable progression-free survival and overall survival. Neither SM nor MPF showed prognostic value.

Conclusions: SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response in mesothelioma. Baseline OPN levels were an independent negative predictor of survival. These promising results require further validation.

In plain English

This observational study at Belgian hospitals enrolled 62 patients with malignant pleural mesothelioma (53 men, 9 women) between January 2007 and December 2010. Using blood samples matched with CT scans, it tested whether three markers tracked treatment response and predicted survival: soluble mesothelin (SM), megakaryocyte potentiating factor (MPF) and osteopontin (OPN). In five patients sampled before and after extrapleural pneumonectomy, SM and MPF fell in all five, while OPN rose in four. Among 57 patients followed during chemotherapy, SM and MPF fell significantly in patients with partial response, and all three rose significantly in those with progressive disease. SM and MPF matched scans more closely than OPN. Among 48 patients given chemotherapy only, those with baseline OPN below 862.78 ng/ml had median progression-free survival of 14.3 months (95% CI 8.5 to 20.1), versus 5.6 months (95% CI 4.4 to 6.8) for the others. SM and MPF showed no prognostic value, though the authors said these analyses lacked power. The authors concluded that SM and MPF might prove useful in monitoring response but need further validation. Asbestos exposure was not reported.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective, observational multicenter study of blood biomarkers, compared with CT-scan response and survival
• Who was studied: 62 patients with malignant pleural mesothelioma (53 males, 9 females; median age 64 years), included at diagnosis at Belgian hospitals between January 2007 and December 2010. Overall-survival follow-up ran to February 1, 2011. 48 patients received chemotherapy only and 14 received multimodality therapy.
• Exposure: Not asbestos exposure. The study measured serum SM and MPF and plasma OPN at diagnosis and during and after treatment (pemetrexed plus a platinum agent, and in some patients extrapleural pneumonectomy). Patients' asbestos exposure was not reported.
• Main results:
  • In the 5 patients sampled before and after extrapleural pneumonectomy, SM and MPF fell in all five (median fall 78% and 76%), while OPN rose in four (median rise 20%)
  • Of the 57 patients followed during chemotherapy, 27 (47%) had stable disease, 14 (25%) partial response and 16 (28%) progressive disease as best overall response
  • In patients with stable disease, SM and MPF did not change significantly while OPN decreased significantly. In partial response, SM and MPF decreased significantly while OPN did not change significantly. In progressive disease, all three increased significantly.
  • Relative changes in SM and MPF matched radiological response more accurately than OPN. For progressive disease, sensitivity was 81% (13/16) for SM, 81% (13/16) for MPF and 38% (6/16) for OPN.
  • In 48 chemotherapy-only patients, those with baseline OPN below 862.78 ng/ml had median progression-free survival of 14.3 months (95% CI 8.5–20.1), versus 5.6 months (95% CI 4.4–6.8) for the others. In the multivariate model this threshold had HR 2.912 (95% CI 1.286–6.596).
  • In the same 48 patients, those with baseline OPN below 1141.11 ng/ml had median overall survival of 18.9 months (95% CI 14.6–23.1), versus 10.1 months (95% CI 5.5–14.7) for the others. In the multivariate model this threshold had HR 2.216 (95% CI 1.050–4.678). Baseline CRP was also associated with both outcomes.
  • Neither SM nor MPF predicted progression-free or overall survival
• The authors' conclusion: The authors concluded that SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response. They also concluded that low baseline OPN was independently associated with better progression-free and overall survival, and that further validation in larger prospective trials is necessary.
• Limitations the authors state:
  • Because the study was observational and exploratory, blood sampling and CTs were not mandatory, so follow-up and time between samples were not uniform across patients
  • Only a limited number of patients were followed up after completing therapy
  • The number of patients was relatively small, so the findings need further validation
  • The survival analyses rested on a relatively low number of events and lacked power, so the negative findings for SM and MPF should be interpreted with caution
  • Only five patients had samples before and after surgery, too few for robust statistical analysis

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelin, Osteopontin, Mesothelioma, Biomarker, Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Chemotherapy, Progression-Free Survival.

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• Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2010)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study — F. Bruno, D. Baratti, et al. (2018)
• Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: evaluation in comparison with mesothelin — K. Iwahori, T. Osaki, et al. (2008)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)

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