A prospective study to investigate the role of serial serum mesothelin in monitoring mesothelioma

Our plain-English summary of A prospective study to investigate the role of serial serum mesothelin in monitoring mesothelioma, by D. de Fonseka, D.T. Arnold, L. Stadon, et al (BMC Cancer, 2018).

The study

• Authors: D. de Fonseka, D.T. Arnold, L. Stadon, A. Morley, E. Keenan, M. Darby, L. Armstrong, P. Virgo, N.A. Maskell
• Journal: BMC Cancer
• Published: 2018;18(1):199
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Radiological monitoring of malignant pleural mesothelioma (MPM) using modified RECIST criteria is limited by low sensitivity and inter-observer variability. Serial serum mesothelin measurement has shown utility in the assessment of treatment response during chemotherapy but has never been assessed in the longer term follow up of patients.

Methods: This is a single centre study of consecutive patients diagnosed with MPM who received chemotherapy or best supportive care (BSC). Serum mesothelin measurements with paired 6 monthly CT scans were performed following the completion of chemotherapy, or from baseline in the BSC group. Changes in mesothelin were correlated with radiological progression and overall survival.

Results: Forty-one patients with MPM were recruited and followed up for a minimum of 12 months (range 12-21 months). The majority of patients (n = 23) received chemotherapy with pemetrexed and cisplatin. Across the cohort a 10% rise in serum mesothelin could predict radiological progression with a sensitivity of 96% (IQR; 79-100) and specificity of 74% (IQR; 50-91). Sensitivity fell to 80% in sarcomatoid only disease. Patients with a rising mesothelin at 6 months had significantly worse overall survival (175 days) compared to stable/falling levels (448 days) (p = 0.003).

Conclusions: This is the first study to assess serum mesothelin's ability to detect progression of MPM following chemotherapy or during BSC. A 10% rise in serum mesothelin level showed excellent sensitivity at predicting progressive disease. Mesothelin measurement has several advantages over serial CT imaging including reducing hospital visits and cost.

In plain English

This single-centre prospective study followed 41 patients with malignant pleural mesothelioma, recruited 2014 to 2016; 23 had pemetrexed and cisplatin chemotherapy and 18 had none. It asked whether repeated mesothelin blood tests could track disease after chemotherapy or during best supportive care. Mesothelin results were paired with CT scans taken within 31 days, giving 43 comparisons. With a 10% rise as cut-off, sensitivity for progression on clinically reported CT was 95.8% (reported range 78.8 to 99.8) and specificity 73.7% (48.8 to 90.8). Sensitivity was 100% (75.3 to 100) with baseline levels of 2 nmol/L or more (19 comparisons) and 80.0% (28.4 to 99.5) in non-epithelioid disease (9 comparisons, 5 progressing). Patients whose mesothelin rose at least 10% at 6 months had median survival from sampling of 175 days, versus 448 for stable or falling levels (p = 0.003). Allowing for age, tumour type and treatment, this difference was no longer statistically significant. The authors concluded that rising mesothelin is a sensitive progression marker that could be a cost-effective addition or alternative to repeated CT scans; they noted the small cohort.

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 cohort study at a single centre, run alongside normal clinical care (longitudinal biomarker study)
• Who was studied: 41 consecutive adults with histocytologically confirmed malignant pleural mesothelioma, recruited February 2014 to October 2016 (UK, South West research ethics committee). 35 were men and 6 women, with a median age of 72 (range 58–83). 23 received pemetrexed and cisplatin chemotherapy and 18 received no chemotherapy.
• Exposure: Not an asbestos-exposure study; no fiber types or asbestos exposure are reported. The factor studied was serum mesothelin, measured with the commercial Mesomark ELISA test and compared with CT scans read clinically and by modified RECIST criteria. Rises of 10%, 15% and 25% were tested as cut-offs.
• Main results:
  • There were 43 paired mesothelin–CT comparisons: 25 in the post-chemotherapy group and 18 in the non-chemotherapy group.
  • Across all 43 comparisons, a 10% rise in mesothelin predicted progression on the clinically reported CT with a sensitivity of 95.8 (78.8–99.8) and a specificity of 73.7 (48.8–90.8). The table does not label what the ranges are.
  • Using the 10% cut-off, the authors report an accuracy of 86% for detecting progression.
  • Median mesothelin did not change (0.0 nmol/l) in comparisons without progression on clinically reported CT. It rose by 1.8 nmol/l (IQR 0.7–1.8) in comparisons with radiological progression (p < 0.001).
  • Mesothelin changes matched the clinically reported CT better than modified RECIST (mRECIST) reporting, whichever cut-off was used.
  • There were 19 comparisons with a baseline mesothelin of 2 nmol/L or more, 13 of them showing progression. In this group, sensitivity was 100 (75.3–100).
  • There were 24 comparisons with a baseline mesothelin below 2 nmol/L. In this group, sensitivity was 90.9 (58.7–99.7) and specificity 69.2 (38.5–90.9).
  • There were 9 comparisons in the non-epithelioid subgroup, 5 of them showing progression. In this group, sensitivity was 80.0 (28.4–99.5) and specificity 75.0 (19.4–99.4).
  • At 6 months, patients with a rising mesothelin (10% cut-off) had shorter survival measured from the date of sampling. Their median was 175 days (IQR 80–211), compared with 448 days (IQR 321 to 554) for falling or stable levels (p = 0.003).
  • In a multivariate analysis including age, histological subtype and treatment, neither change in mesothelin nor clinically reported CT remained statistically significant.
  • Baseline mesothelin level did not predict survival. Median survival was 329 days for a low level (under 2 nmol/L) versus 452 days for a high level, p = 0.191.
• The authors' conclusion: The authors concluded that a rising serum mesothelin is a sensitive marker of progression in the follow-up of patients with malignant pleural mesothelioma. They also concluded that regular mesothelin tests could be a cost-effective adjunct or alternative to serial CT scanning.
• Limitations the authors state:
  • The cohort was small, which affects the multivariate analyses.
  • Because the study was observational, some mesothelin samples were not matched by a scan within one month.
  • Because patients were not on treatment, there were few instances of falling mesothelin.
  • Renal function, which can falsely raise mesothelin, was not reassessed during follow-up.
  • The reference standard (mRECIST CT) is insensitive at detecting early progression, and many scans were non-measurable by mRECIST.
  • The low-baseline subgroup was small, so no firm recommendations can be made about retesting when the baseline level is low.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma, Pleural Mesothelioma, Modified RECIST (mRECIST), Chemotherapy, CT Scan, Overall Survival, Pemetrexed (Alimta).

Related studies

• Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study — K. Hollevoet, J. Van Cleemput, et al. (2011)
• The Correlation of Serum Mesothelin Level With Pleural Thickness in Malignant Pleural Mesothelioma Makes it a Valuable Tool for Monitoring Tumor Progression — V. Fontana, A. Vigani, et al. (2019)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• A prospective trial evaluating the role of mesothelin in undiagnosed pleural effusions — C.E. Hooper, A.J. Morley, et al. (2013)
• Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos — R. Filiberti, P. Marroni, et al. (2014)

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