The impact of geographic and socioeconomic factors upon MPM incidence and prognosis in MPM?
Investigators: Linton A1, Soeberg M1,2, Broome R3, van Zandwijk N1,2.
1. Asbestos Diseases Research Institute, 2. University of Sydney, 3. Public Health Observatory
The impact of clinico-pathological factors such as age, gender, and histological subtype on the prognosis of malignant pleural mesothelioma (MPM) is well understood. However, socio-economic and geographic factors and their impact on survival have been studied to a lesser extent. Whilst the majority of Australians live in major metropolitan centres, a significant proportion of the population reside in smaller regional centres and surrounding areas. As such access to clinical services including specialist oncological units may be limited. Furthermore, socio-economic factors may further impact service access, treatment provision and prognosis. With the cooperation of the NSW Dust Diseases Board and oncology and thoracic units across NSW, we have performed one of the largest analyses to date of Australian patients diagnosed with MPM. Gathering data from the medical and surgical records of 910 patients diagnosed between 2002 and 2009, we are studying the impact of socio-economic advantage and disadvantage, proximity to an oncological multi-disciplinary team meeting and geographic remoteness upon treatment utilisation and survival. Furthermore we are analysing the distribution of MPM diagnoses across NSW in comparison to those identified by the Cancer Institute NSW, to assess the appropriateness of cancer service distribution and the scope of DDB utilisation in NSW.
MesomiR 1: The phase I study testing TargomiRs in patients with recurrent malignant pleural mesothelioma
Investigators: van Zandwijk N1,2, Bailey D3, Pavlakis N4, Clarke S4, Kao S1,5, Boyer M5, Linton A1,6, Cooper W7, Reid G1,2.
1. Asbestos Diseases Research Institute, 2. University of Sydney, 3. Royal North Shore Hospital, 4. Northern Cancer Institute, 5. Chris O’Brien Lifehouse, 6. Concord Repatriation General Hospital, 7. Royal Prince Alfred Hospital
After studying different drug doses and administration schedules of TargomiRs (Epidermal Growth Factor Receptor (EGFR) antibody targeted EnGeneIC Delivery Vesicles (EDVs) packaged with microRNA mimics) in 24 patients a more accurate picture of drug-associated reactions has emerged. TargomiRs are rather well tolerated. The side effects observed are the consequence of the inflammatory response elicited by intravenous administration of EDVs and most patients experience transient shivering/rigor, and temperature elevation, sometimes accompanied by discomfort/pain at the disease site. Early signs of clinical activity (reduction/stabilisation of tumour size) of TargomiRs has been noted and one particular impressive response has been published in the American Journal of Respiratory and Critical Care Medicine (June 2015). It is expected that dose escalation studies will continue until the end of 2016 and will be followed by a formal phase II study concentrating on the efficacy of TargomiRs. A detailed protocol for the execution of the phase II study is in preparation. Abstracts documenting study progress have been submitted to COSA, the International Mesothelioma Interest Group (iMig) and the International Association for the Study of Lung Cancer 2015 and 2016.
Clinicopathological review of asbestos-associated lung cancer from Dust Diseases Board
Investigators: Kao S1,3, Lin RCY1,7, Hannaford-Turner K2, Hyland R1, Cooper W4, Klebe S5, Reid G1,6, van Zandwijk N1,6.
1. Asbestos Diseases Research Institute, 2. Dust Diseases Authority, 3. Chris O’Brien Lifehouse, 4. Royal Prince Alfred Hospital, 5. Flinders University, 6. University of Sydney, 7. University of New South Wales
Despite the extensive epidemiological literature available, the molecular relationship between asbestos exposure and lung cancer remains the subject of controversy. Essentially, this relates to the fact that most asbestos-associated lung cancers occur in those who are also cigarette smokers, and smoking represents the strongest risk factor for lung cancer. It is estimated that asbestos-related lung cancer accounts for 4–12% of all lung cancers worldwide. For every case of malignant mesothelioma, there may be two asbestos-related lung cancers, and this ratio may increase in occupations with heavy asbestos exposures. This study is a review of a retrospective cohort of New South Wales workers with lung cancer who have applied for compensation through the Dust Diseases Board (DDB) between 2002 and 2011. This project aims to investigate whether the spectrum of clinicopathological characteristics and molecular mutations differ between patients with heavy asbestos exposure and those with insufficient and/or no asbestos exposure. The intention is also to determine whether there are any lung cancer biomarkers that are associated with asbestos exposure. This work will pave the way for identification of novel biomarkers in lung cancer tumour samples that are specifically related to asbestos exposure, thereby assisting the DDB in process of assigning asbestos dust exposure as having had material contribution to the development of lung cancer. This work will also provide an accurate overview of the clinical, pathological and molecular characteristics of asbestos related lung cancers and non-asbestos related lung cancers in NSW workers and highlight any differences that might exist between the two groups. So far, we have examined a cohort of 467 patients and 60% were diagnosed with stage 4 disease. We are currently finalising the asbestos exposure data and treatment details. Analyses of the clinical data is expected in 2016 and molecular characterisation will follow shortly after that. The findings of this research will also provide valuable insight into the treatment patterns and survival outcomes of asbestos related lung cancers.