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

Federica Grosso,Sara Delfanti,Michela Lia,Vincenzo Fontana,Matilde Mannucci,Marinella Bertolotti,Maria Pia Pistillo,Stefano Barbero,Antonella Vigani,Francesca Ugo,Roberto Guaschino,Silvio Roncella,Paola Ferro,Ugo Giannoni,Maurizio Cassinari,Antonina Maria De Angelis

doi:10.3390/diagnostics11112015

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.

Highlights

Pleural mesothelioma (PM) is a rare cancer of the mesothelial surfaces with dismal prognosis
The diagnosis was based on histological examination of tumor samples obtained by means of thoracoscopy or computed tomography (CT) guided biopsy and analyzed through the appropriate immunohistochemistry according to international reference guidelines [20]
The study sample included 58 PM patients (40 from AL and 18 from SP) diagnosed in the period 2010–2017 and characterized by an individual profile composed of age at diagnosis, months from diagnosis to the first soluble mesothelin-related peptide (SMRP) measurement, years of follow-up, gender, histology, Eastern Cooperative Oncology Group performance status (ECOG-PS), and vital status at the end of follow-up and treatment (Table 1)

Summary

Introduction

Pleural mesothelioma (PM) is a rare cancer of the mesothelial surfaces with dismal prognosis. Since 2004, platinum and antifolates have been the gold standard for the first line treatment of patients with advanced disease with a median OS of 12 months [3]. In the phase III pivotal trial CheckMate 743, the combination of nivolumab plus ipilimumab significantly prolonged OS with respect to standard chemotherapy [4]. There is no approved second line, the combination of ramucirumab and gemcitabine showed significant OS improvements over gemcitabine in the phase II RAMES study and nivolumab in the salvage setting remarkably improved progression-free and OS in the phase III placebo-controlled CONFIRM trial [5,6,7]. There is still an urgent need for active therapies in this disease and for tools that could assist clinicians in improving the management of patients

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Conclusion