Pilot Study to Evaluate Serum Soluble Mesothelin-Related Peptide (SMRP) as Marker for Clinical Monitoring of Pleural Mesothelioma (PM): Correlation with Modified RECIST Score

Our plain-English summary of Pilot Study to Evaluate Serum Soluble Mesothelin-Related Peptide (SMRP) as Marker for Clinical Monitoring of Pleural Mesothelioma (PM): Correlation with Modified RECIST Score, by F. Grosso, M. Mannucci, F. Ugo, et al (Diagnostics, 2021).

The study

• Authors: F. Grosso, M. Mannucci, F. Ugo, P. Ferro, M. Cassinari, A. Vigani, A.M. De Angelis, S. Delfanti, M. Lia, R. Guaschino, S. Barbero, S. Roncella, U. Giannoni, M. Bertolotti, M.P. Pistillo, V. Fontana
• Journal: Diagnostics
• Published: 2021;11(11)
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker for diagnosis of pleural mesothelioma (PM) and the most used for monitoring treatment. Radiological assessment of PM, based on modified RECIST (mRECIST) criteria, is challenging. This pilot study was designed to evaluate whether SMRP levels correlated over time with mRECIST score. Serial serum samples from PM patients were collected and SMRP levels were measured and compared with the mRECIST score obtained through centralized CT scans by blinded review. The within-patient SMRP-mRECIST relationship over time was estimated through a normal random-effects regression approach applied to the log-transformed mRECIST score. Overall, 58 PM patients were included (46 males and 12 females) with a median age at diagnosis of 67 years (min-max = 48-79), 44 (76%) with epithelioid and 14 (24%) with non-epithelioid histology. The total number of SMRP measurements and CT scans considered for analysis was 183. There was a statistically significant correlation between SMRP and mRECIST score in the 2 cohorts considered both separately and jointly. These results, although exploratory, suggest that SMRP measurement might be considered as an adjunct to monitor PM patients in order to delay CT scans time interval, thus warranting further investigation.

In plain English

This retrospective, observational pilot study from two hospitals in northern Italy (Alessandria and La Spezia) examined whether blood levels of soluble mesothelin-related peptide (SMRP), a protein released by mesothelioma cells, changed over time along with tumor extent on CT scans in people with pleural mesothelioma. It included 58 patients: 40 from Alessandria and 18 from La Spezia. One expert radiologist, who did not know the clinical data or SMRP results, scored the CT scans using modified RECIST (mRECIST) criteria. Each scan was paired with the closest SMRP measurement, giving 183 measurements in total. The article did not report on asbestos exposure. Within patients, each doubling of SMRP went with an mRECIST score about 16% higher in the Alessandria cohort (GMR 1.16, 95% CL 1.11–1.22) and about 18% higher in the La Spezia cohort (GMR 1.18, 95% CL 1.06–1.31). In both cohorts combined, the GMR was 1.19 (95% CL 1.13–1.25). Results were similar for epithelioid and non-epithelioid tumors. The authors concluded that SMRP could be a reliable biomarker for monitoring progression. They cautioned that the study was small, lacked a set sampling schedule, and needs confirmation.

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, observational pilot study using repeated (longitudinal) measurements analyzed with random-effects regression
• Who was studied: 58 patients with pleural mesothelioma in two Italian cohorts. The Alessandria cohort (40 patients) was recruited from June 2014 to April 2020. The La Spezia cohort (18 patients) was recruited from March 2010 to May 2015, with follow-up ending September 2017. The patients were 46 males and 12 females, median age 67; 44 had epithelioid and 14 had non-epithelioid histology.
• Exposure: Asbestos exposure was not reported. The factor studied was serum SMRP level, measured with a CLEIA kit (Lumipulse G Mesothelin) for Alessandria samples and an ELISA kit (MesoMark) for La Spezia samples, compared with mRECIST scores from centrally reviewed CT scans.
• Main results:
  • Alessandria patients had 141 mRECIST measurements and La Spezia patients had 42 (183 in total), each paired with the closest SMRP measurement.
  • Alessandria cohort: each doubling of SMRP was associated with an mRECIST score about 16% higher (GMR = 1.16, 95% CL = 1.11–1.22; p less than 0.001).
  • La Spezia cohort: each doubling of SMRP was associated with an mRECIST score about 18% higher (GMR = 1.18, 95% CL = 1.06–1.31; p-value printed as less than 0.003 in the text, 0.003 in Table 3).
  • Both cohorts combined: GMR = 1.19 (95% CL = 1.13–1.25; p less than 0.001) per doubling of SMRP.
  • By histology: epithelioid GMR = 1.20 (95% CL = 1.13–1.27); non-epithelioid GMR = 1.17 (95% CL = 1.10–1.25).
  • When SMRP was grouped into quartiles, mean mRECIST scores rose by about 15–20% from each SMRP category to the next.
• The authors' conclusion: The authors concluded that their exploratory proof-of-concept study confirmed that SMRP could be a reliable biomarker for monitoring pleural mesothelioma progression. They also said the data must be taken with caution and need confirmatory cohort studies.
• Limitations the authors state:
  • Small sample size and no specific timeline for collecting samples.
  • The two cohorts differed in treatments, length of follow-up and the assay used to measure SMRP (CLEIA in Alessandria, ELISA in La Spezia). The authors argued that within-patient comparisons took this into account.
  • The authors said the data must be taken with caution and need further confirmatory cohort studies.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Pleural Mesothelioma, Modified RECIST (mRECIST), Biomarker, CT Scan, Epithelioid, Non-epithelioid.

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• Soluble mesothelin-related peptides (SMRP) - high stability of a potential tumor marker for mesothelioma — D.G. Weber, D. Taeger, et al. (2007)
• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)
• 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)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• Two novel polymorphisms in 5' flanking region of the mesothelin gene are associated with soluble mesothelin-related peptide (SMRP) levels — A. Cristaudo, R. Foddis, et al. (2011)
• 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 — S.I. Katz, L. Roshkovan, et al. (2021)

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