Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial

Our plain-English summary of Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial, by S.I. Katz, L. Roshkovan, I. Berger, et al (Lung Cancer, 2021).

The study

• Authors: S.I. Katz, L. Roshkovan, I. Berger, J.S. Friedberg, E.W. Alley, C.B. Simone, A.R. Haas, K.A. Cengel, D.H. Sterman, S.M. Albelda
• Journal: Lung Cancer
• Published: 2021;154:5-12
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Soluble mesothelin-related protein (SMRP) and fibulin-3 serum levels may serve as diagnostic and prognostic biomarkers of malignant pleural mesothelioma (MPM). Here, we evaluate these markers for correlation to tumor volume, prognosis and response assessment in a clinical trial of immunogene therapy in combination with chemotherapy.

Materials And Methods: Serial serum levels of SMRP and fibulin-3 were measured in adult patients with biopsy-proven MPM enrolled in two prospective clinical trials. Pre-therapy computed tomography (CT) measurements of tumor burden were calculated and correlated with pre-therapy serum SMRP and fibulin-3 levels in these two trials. Serological data were also correlated with radiological assessment of response using Modified RECIST criteria over the first 6 months of intrapleural delivery of adenovirus-IFN alpha (Ad.IFN-α) combined with chemotherapy.

Results: A cohort of 58 patients who enrolled in either a photodynamic therapy trial or immunotherapy clinical trial had available imaging and SMRP serological data for analysis of whom 45 patients had serological fibulin-3 data. The cohort mean total tumor volume was 387 cm3 (STD 561 cm3). Serum SMRP was detectable in 57 of 58 patients (mean 3.8 nM, STD 6.0). Serum fibulin-3 was detected in 44 of 45 patients (mean 23 ng/mL, STD 14). At pre-therapy baseline in these two trials, there was a strong correlation between tumor volume and serum SMRP levels (r = 0.61, p < 0.001), and a moderate correlation between tumor volume and serum fibulin-3 levels (r = 0.36, p = 0.014). Twenty-eight patients in the immunotherapy trial had longitudinal serologic and radiographic data. Fold-changes in SMRP and fibulin-3 did not show significant correlations with modified RECIST measurements.

Conclusions: Although our data show correlations of SMRP and fibulin-3 with initial tumor volumes as measured by CT scanning, the use of SMRP and fibulin-3 as serological biomarkers in the immunotherapy trial were not useful in following tumor response longitudinally.

Copyright © 2021. Published by Elsevier B.V.

In plain English

This study looked back at blood-test and CT-scan data from 58 adults with biopsy-proven malignant pleural mesothelioma treated in two clinical trials at one institution. One trial combined surgery with photodynamic therapy. The other gave immunogene therapy (Ad.IFN-α, delivered into the chest lining) followed by chemotherapy. The authors compared two blood markers, SMRP and fibulin-3, with tumor volume measured on CT before treatment. Higher SMRP levels went with larger tumors, a strong and statistically significant correlation (r = 0.61). Fibulin-3, measured in 46 patients, showed a moderate but significant correlation (r = 0.36, p = 0.014). Eleven of the 12 patients with sarcomatoid or mixed tumors had SMRP below 2.0 nM. In 28 immunotherapy-trial patients, changes in neither marker significantly correlated with tumor changes measured by modified RECIST criteria. Response categories matched in 46% of cases for SMRP and in 9 of 22 cases (41%) for fibulin-3. The authors concluded that, at least in this trial, neither marker was useful for following tumor response. They named the modest sample size and the single treatment regimen as limitations. The study did not examine asbestos exposure.

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: Retrospective analysis of data from two prospective clinical trials at a single institution
• Who was studied: 58 adults with biopsy-proven malignant pleural mesothelioma (mean age 67; 46 male, 12 female; 46 epithelial, 12 biphasic or sarcomatoid). 20 came from a surgery/photodynamic therapy trial and 38 from an Ad.IFN-α immunotherapy trial at the University of Pennsylvania. Longitudinal analysis used 28 patients, and 14 for the 6-month trajectory analysis.
• Exposure: Not an asbestos exposure study. The factors studied were blood (serum) levels of SMRP and fibulin-3, measured by ELISA, compared with CT tumor volume and with tumor response to Ad.IFN-α immunogene therapy plus chemotherapy.
• Main results:
  • Before treatment, across all 58 patients, serum SMRP strongly correlated with CT tumor volume (r = 0.61, p < 0.001)
  • Before treatment, serum fibulin-3 (46 patients) showed a moderate but significant correlation with tumor volume (r = 0.36, p = 0.014)
  • Only 19 of the 58 patients (33%) had baseline SMRP above the 2.5 nM threshold
  • 11 of the 12 patients with sarcomatoid or mixed histology had SMRP levels below 2.0 nM
  • In 28 immunotherapy-trial patients, fold-change in modified RECIST measurements did not significantly correlate with fold-change in SMRP (r = 0.28, p = 0.15) or in fibulin-3 (r = 0, p = 0.74)
  • At the first follow-up time point, response categories based on SMRP matched modified RECIST in 46% of patients (13 of 28). Those based on fibulin-3 matched in 9 of 22 cases (41%).
  • Over up to 6 months in 14 patients, the SMRP trajectory matched modified RECIST in 8 of 14 (57%) and fibulin-3 in 6 of 14 (43%). Kappa agreement values were low and not significant.
• The authors' conclusion: The authors concluded that, at least in their immunotherapy trial, neither SMRP nor fibulin-3 was useful for following tumor response, although both correlated with initial tumor volume. They called for further study in other trial settings.
• Limitations the authors state:
  • Modest sample size, especially for the longitudinal analysis, and limitation to a single treatment regimen
  • No control for patient factors that can affect serum measurements, such as age, kidney function (GFR) and BMI
  • Fibulin-3 was measured in serum rather than plasma
  • Effects of prior therapies on marker levels are unknown
  • The study was not designed to assess diagnostic accuracy

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, Soluble Mesothelin-Related Peptides (SMRP), Fibulin-3, Pleural Mesothelioma, Biomarker, Immunotherapy, Prognosis, Clinical Trial.

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