The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication

• Published in: British journal of cancer Vol. 112; no. 7; pp. 1175 - 1182
• Main Authors: Hooper, C E, Lyburn, I D, Searle, J, Darby, M, Hall, T, Hall, D, Morley, A, White, P, Rahman, N M, De Winton, E, Clive, A, Masani, V, Arnold, D T, Dangoor, A, Guglani, S, Jankowska, P, Lowndes, S A, Harvey, J E, Braybrooke, J P, Maskell, N A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.03.2015; Nature Publishing Group
• Subjects: 692/699/67/1059/99; 692/699/67/1641; 692/699/67/1857; 692/700/1750; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carboplatin - administration & dosage; Cisplatin - administration & dosage; Clinical Study; Cohort Studies; Drug Resistance; Epidemiology; Female; Glutamates - administration & dosage; Guanine - administration & dosage; Guanine - analogs & derivatives; Humans; Lung Neoplasms - blood; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lymphocytes - pathology; Male; Mesothelioma - blood; Mesothelioma - diagnostic imaging; Mesothelioma - drug therapy; Mesothelioma, Malignant; Molecular Medicine; Multimodal Imaging; Neutrophils - pathology; Oncology; Pemetrexed; Positron-Emission Tomography; Prognosis; Prospective Studies; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.62

Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) ( P =0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272–576) days vs NLR⩾4, 257 (IQR 147–490), P =0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) ( P <0.001). Interpretation: Neutrophil–lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients’ treatment response.