Author of

• 15199

  +

  MTE 33 - (Debate on) Prognostic Biomarkers in Mesothelioma (Ticketed Session) (ID 85)

  • Event: WCLC 2015
  • Type: Meet the Expert (Ticketed Session)
  • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 07:00 - 08:00, 201+203

  • 15201

    +

    MTE33.02 - (Debate on) Prognostic Biomarkers in Mesothelioma (ID 2025)

    07:30 - 08:00  |  Author(s): J. Creaney
    • Abstract
    • Presentation

    Abstract:
    Prognosis for mesothelioma is bleak; median survival for the cohort is generally less than 12 months. However individual patients have been known to survive for many years. From the CARET study 5 year survival rates of 9% have been reported. Our own data shows 5 year survival at less than 5%. The most frequent question of newly diagnosed mesothelioma patients relates to their prognosis. Clinical and laboratory prognostic variables proposed nearly two decades ago from consortium data from the European Organisation for Research and Treatment of Cancer (EORTC) (Curran et al, 1998) and the Cancer and Leukaemia Group B (CALGB) (Herndon et al, 1998) have been validated. Prognostic variables including performance status (PS), age, gender, tumour histology, white blood cell count (WCC), haemoglobin (Hb) level, and the presence or absence of chest pain and weight loss are taken into account when giving the patient their prognosis. Clearly, besides tumour histology and possibly the laboratory variables, most relate to the overall health and fitness of the individual. Non-subjectively determined biomarkers have been proposed as an independent means of providing prognostic information. And indeed several markers have been shown in a research setting to reflect prognosis however few of these studies have taken into account the known clinical prognostic factors. The prognostic value of serum concentrations of soluble mesothelin, the most well studied mesothelioma biomarker, have been inconsistent between studies. Data is compromised by study cohort characteristics, as tumours of sarcomatoid histology tend to have low mesothelin levels and poor survival. Our own data suggests that mesothelin levels in patients with epithelioid tumours are reflective of tumour burden as assessed by chest x-ray, CT or PET scans, which itself is an indicator of survival. Several other serological biomarkers have been reported to have prognostic value, including aquaporin 1 and osteopontin. In addition there has been extensive work on inflammation-based prognostic indices, including the neutrophil to lymphocyte ratio as well as serum albumin levels. Another useful source of prognostic biomarkers is tumour associated antigens. We have shown that serum immunoreactivity to the ATP synthase protein ATP5B is positively correlated with prognosis, and have unpublished data showing a similar significant positive association of immunoreactivity to RAB38, a previously described melanoma associated tumour antigen. In addition to blood based biomarkers, in mesothelioma it is also possible to examine soluble biomarkers in the pleural effusion. There is evidence that pleural effusion concentrations of hyaluronic acid and of fibulin-3 may provide independent prognostic data. In the case of hyaluronic acid, higher concentration of this biomarker is associated with a better prognosis. Fibulin-3 has the potential to be a useful prognostic marker because its interpretation is not confounded by lower concentrations associated with a sarcomatoid histopathology; rather sarcomatoid effusions have higher concentrations of this marker and it has been shown to be markedly superior to effusion mesothelin as a prognostic marker. Other prognostic effusion biomarkers that have been identified are syndecan-1 and osteopontin. Recently, several novel pleural effusion based biomarkers have been reported from discovery studies; these include galectin-1, aldo-keto reductase and apoliproptein C-1. Of these high effusion levels of galectin-1 and aldo-keto reductase were associated with a relatively poor prognosis whereas high effusion levels apoliproptein C-1 were associated with improved prognosis. It is important to realize that these findings remain un-validated in other patient cohorts. These biomarkers that have been identified as having prognostic value were generally not initially investigated as prognostic markers, rather they have been studied for this purpose after their identification as potential diagnostic markers. Typically their initial identification has not been thoroughly investigated in independent cohorts of patients, nor have they been systematically investigated together to determine the degree to which they are independent of each other as prognostic markers. It is possible that more suitable markers could be identified that were initially investigated as prognostic markers. An example of this would be the identification of proteins that were under or over expressed in pleural effusions from patients with longer survival compared to those with a shorter survival time using proteomics discovery methods. This underscores the importance of prospective collection of biological samples with scrupulous recording of clinical details for future evaluation of markers as they are discovered.
    
    

    Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.