ABSTRACT
INTRODUCTION: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory. METHODS: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure. RESULTS: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume. CONCLUSIONS: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.
Subject(s)
Asbestos , Lung Neoplasms , Mesothelioma , Pleural Neoplasms , Biomarkers, Tumor , Calcium-Binding Proteins , Extracellular Matrix Proteins , GPI-Linked Proteins , Humans , Lung Neoplasms/diagnosis , Mesothelioma/diagnosis , Mesothelioma/etiology , Pleural Neoplasms/diagnosis , Pleural Neoplasms/etiology , Proteomics , Retrospective StudiesSubject(s)
Early Detection of Cancer/statistics & numerical data , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Tomography, X-Ray Computed/statistics & numerical data , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Medicine/standards , Risk Assessment , Smoking , United Kingdom/epidemiologyABSTRACT
BACKGROUND: The utility of the recently introduced semirigid thoracoscopy in undiagnosed pleural effusions is still unclear. METHODS: A single-center, 4-year retrospective analysis of all semirigid medical thoracoscopy procedures was done. The diagnostic accuracy of thoracoscopy was calculated as the number of positive diagnoses achieved by thoracoscopy in relation to the end-diagnosis achieved in the patient group by any means. RESULTS: One hundred fifty procedures were analyzed. Ninety-two patients (62.3%) were diagnosed as having a malignant disorder, of which mesothelioma was the most common (26%). Pleural thickening and nodularity were the most common abnormalities noted. The combined presence of nodules and hemorrhagic fluid increased the likelihood of malignancy 9-fold. Thirteen patients with a high clinical suspicion of malignancy but negative by thoracoscopy underwent mediastinoscopy, computed tomography-guided biopsy, or open thoracotomy. A malignant etiology was confirmed in all of them. Overall, thoracoscopy provided a diagnostic accuracy of 91.3%, sensitivity of 87%, and specificity of 100%. The addition of a second procedure in selected patients improved the diagnostic accuracy for malignancy by 8.7%. The procedures were well tolerated and only 6 patients developed minor and transient complications such as pain, hypoxia, and bradycardia. CONCLUSION: Semirigid thoracoscopy is a safe, well-tolerated, and efficacious procedure for establishing the diagnosis in pleural effusions of undetermined etiology.
