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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.

Publication ,  Journal Article
Katz, SI; Roshkovan, L; Berger, I; Friedberg, JS; Alley, EW; Simone, CB; Haas, AR; Cengel, KA; Sterman, DH; Albelda, SM
Published in: Lung cancer (Amsterdam, Netherlands)
April 2021

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.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.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.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.

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Published In

Lung cancer (Amsterdam, Netherlands)

DOI

EISSN

1872-8332

ISSN

0169-5002

Publication Date

April 2021

Volume

154

Start / End Page

5 / 12

Related Subject Headings

  • Tumor Burden
  • Prospective Studies
  • Pleural Neoplasms
  • Oncology & Carcinogenesis
  • Mesothelioma, Malignant
  • Mesothelioma
  • Mesothelin
  • Lung Neoplasms
  • Immunotherapy
  • Humans
 

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Katz, S. I., Roshkovan, L., Berger, I., Friedberg, J. S., Alley, E. W., Simone, C. B., … Albelda, S. M. (2021). 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. Lung Cancer (Amsterdam, Netherlands), 154, 5–12. https://doi.org/10.1016/j.lungcan.2021.01.011
Katz, Sharyn I., Leonid Roshkovan, Ian Berger, Joseph S. Friedberg, Evan W. Alley, Charles B. Simone, Andrew R. Haas, Keith A. Cengel, Daniel H. Sterman, and Steven M. Albelda. “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.Lung Cancer (Amsterdam, Netherlands) 154 (April 2021): 5–12. https://doi.org/10.1016/j.lungcan.2021.01.011.
Katz SI, Roshkovan L, Berger I, Friedberg JS, Alley EW, Simone CB, Haas AR, Cengel KA, Sterman DH, Albelda SM. 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. Lung cancer (Amsterdam, Netherlands). 2021 Apr;154:5–12.
Journal cover image

Published In

Lung cancer (Amsterdam, Netherlands)

DOI

EISSN

1872-8332

ISSN

0169-5002

Publication Date

April 2021

Volume

154

Start / End Page

5 / 12

Related Subject Headings

  • Tumor Burden
  • Prospective Studies
  • Pleural Neoplasms
  • Oncology & Carcinogenesis
  • Mesothelioma, Malignant
  • Mesothelioma
  • Mesothelin
  • Lung Neoplasms
  • Immunotherapy
  • Humans