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. 2021 Apr:154:5-12. doi: 10.1016/j.lungcan.2021.01.011. Epub 2021 Jan 14.

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.

Keywords: Ad.IFN; Biomarkers; Computed tomography; Fibulin; Mesothelin; Mesothelioma; Volumes.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • GPI-Linked Proteins
  • Humans
  • Immunotherapy
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / therapy
  • Mesothelin
  • Mesothelioma* / diagnosis
  • Mesothelioma* / therapy
  • Mesothelioma, Malignant*
  • Pleural Neoplasms* / therapy
  • Prospective Studies
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • GPI-Linked Proteins
  • fibulin
  • Mesothelin