title: The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK [2] North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK.
authors.forename: C E
authors.initials: CE
authors.lastname: Hooper
authors.affiliation: Cobalt Health, Thirlestaine Road, Cheltenham GL53 7AS, UK.
authors.forename: I D
authors.initials: ID
authors.lastname: Lyburn
authors.affiliation: Cobalt Health, Thirlestaine Road, Cheltenham GL53 7AS, UK.
authors.forename: J
authors.initials: J
authors.lastname: Searle
authors.affiliation: Department of Radiology, Southmead Hopsital, North Bristol NHS Trust, Bristol BS10 5NB, UK.
authors.forename: M
authors.initials: M
authors.lastname: Darby
authors.affiliation: Department of Radiology, Royal United Bath Hospital, Bath BA1 3NG, UK.
authors.forename: T
authors.initials: T
authors.lastname: Hall
authors.affiliation: Cobalt Health, Thirlestaine Road, Cheltenham GL53 7AS, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hall
authors.affiliation: North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK.
authors.forename: A
authors.initials: A
authors.lastname: Morley
authors.affiliation: Applied Statistics Group, University of West of England (UWE), Bristol BS16 1QY, UK.
authors.forename: P
authors.initials: P
authors.lastname: White
authors.affiliation: Oxford Respiratory Clinical Trial Unit (Funded by the NIHR Biomedical Research Centre), Churchill Hospital, Oxford OX3 7LJ, UK.
authors.forename: N M
authors.initials: NM
authors.lastname: Rahman
authors.affiliation: Department of Oncology, Royal United Hospital Bath BA1 3NG, UK.
authors.forename: E
authors.initials: E
authors.lastname: De Winton
authors.affiliation: Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: A
authors.initials: A
authors.lastname: Clive
authors.affiliation: Department of Respiratory Medicine, Royal United Hospital Bath BA1 3NG, UK.
authors.forename: V
authors.initials: V
authors.lastname: Masani
authors.affiliation: Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: D T
authors.initials: DT
authors.lastname: Arnold
authors.affiliation: Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol BS2 8ED, UK.
authors.forename: A
authors.initials: A
authors.lastname: Dangoor
authors.affiliation: Department of Oncology, Cheltenham General Hospital, Cheltenham GL53 7AN, UK.
authors.forename: S
authors.initials: S
authors.lastname: Guglani
authors.affiliation: Department of Oncology, Musgrove Park Hospital, Severn Drive, Taunton TA1 5DA, UK.
authors.forename: P
authors.initials: P
authors.lastname: Jankowska
authors.affiliation: Department of Oncology, Great Western Hospital, Swindon SN3 6BB, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Lowndes
authors.affiliation: North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Harvey
authors.affiliation: Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol BS2 8ED, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Braybrooke
authors.affiliation: 1] Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK [2] North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Maskell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008175:Lung Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D008214:Lymphocytes / Q000473:pathology; D008654:Mesothelioma / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D000086002:Mesothelioma, Malignant; D064847:Multimodal Imaging; D009504:Neutrophils / Q000473:pathology; D000068437:Pemetrexed; D049268:Positron-Emission Tomography; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D016190:Carboplatin; D002945:Cisplatin; D005971:Glutamates; D006147:Guanine; D000068437:Pemetrexed