Malignant Mesothelioma: an Update

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1 Malignant Mesothelioma: an Update Nico van Zandwijk Asbestos Diseases Research Institute Bernie Banton Centre University of Sydney Australia Physicians Week RACP

2 Health Risks of Asbestos Fibers Asbestos Fibres Malignant Mesothelioma Asbestos Fibres Lung Cancer Asbestos Fibres increase the Risk of Lung Cancer in Smokers Asbestos Fibres Asbestosis

3 Pleural plaques Pleural plaques Asbestosis Pleural mesothelioma

4 Occupations and Locations with an Increased Risk of Asbestos Exposure Manufacturing of Asbestos products Shipyard workers Navy veterans Miners and Drillmen Demolition Workers Railroad workers Construction (insulation) workers Maritime Workers Oil refinery Workers Power plants Automobile reapir Maintenance workers Steel mills Refineries Sand or abrasive manufacturers Paper Mills Drywall Removers

5 World Production of Asbestos

6 Asbestos Consumption and Mesothelioma Deaths Nawrot, Lancet 2007 Lin, Lancet 2007

7 Epidemiology of Malignant Mesothelioma (MM) Peak Asbestos Consumption in Australia in 1975 (90% in asbestos cement industry) First documented MM case in Australia in 1947 The Incidence of Mesothelioma is expected to increase and peak ( between 2015 and 2020? or even later) Latency Period What about Asbestos present in the Society?

8 Naturally Occurring Asbestos in Eastern Australia Potential asbestos-bearing rocks account for about 0.2% of land area of eastern Australia Government authorities and private enterprise need to take geological factors into account to reduce the likelihood of unplanned disturbance of natural asbestos-bearing materials Hendricks M, Environ Geol 2009 M. Hendrickx Environ Geol 2009

9 Malignant Mesothelioma Rising Incidence cases/year in NSW cases in Australia

10 Continued Asbestos Exposure in the Third World

11 Pathogenesis Mesothelioma Asbestos Fibres: Size and Form related to Risk Chronic Inflammation (Genes) Latency Period Life Style? Virus? Immune System (Genes) Mutations Growth Factors Needed is catalogue of genomic changes!

12 Asbestos Exposure & Malignant Mesothelioma Risk Genes Lifestyle? Exposure: Environmental? Occupational What is the Psychological Burden of the Knowledge of Past Asbestos Exposure?

13 Malignant Mesothelioma Originates in the mesothelium surrounding lungs, heart and abdominal organs

14 Symptoms of Mesothelioma Shortness of Breath Pain/Tightness Chest Malaise Weight Loss Pleural Effusion Pleural Thickening Chest Wall invasion (peritoneum)

15 Diagnosis &Treatment of Mesothelioma Earlier Diagnosis may offer an Opportunity for Better Treatment Markers for Early Diagnosis? Pathological Diagnosis needed (expertise!) Radical Treatments better investigated Significant Expertise of Medical Team needed Oncology: High-Volume Institutions seem to perform better

16 Surgical resection in MM Goal of surgery in MM is to remove all gross disease Complete resection is impossible since neither an ExtraPleural Pneumonectomy (EPP) nor a Pleurectomy/Decortication(P/D) can eradicate all (microscopic) disease The decision to perform EPP or P/D is driven primarily by surgeon Flores, J Thor Cardiovasc Surg 2008

17 Retrospective analysis of 663 consecutive MM patients ( ) Operative mortality Local recurrence Distant recurrence Stage I EPP N=385 7% 33% 66% Overall Survival 14 months 5 year survival 12% 38 months P/D N=278 4% 65% 35% Stage II Stage III Stage IV 19 months 11 months 7 months Flores, J Thor Cardiovasc Surg 2008

18 UK MARS trial: Mesothelioma And Radical Surgery trial 670 pts 3 cycles induction chemotherapy R A N D O M I Z E EPP + Adjuvant RT No surgery Primary endpoint: Overall survival Secondary endpoint: QOL

19 Neo-adjuvant multimodality trials in MM: Chemo EPP +/-RT Chemo N # EPP RR PFS (mo) MST (mo) Weder 2004 Gem Cis X % Flores 2006 Gem Cis x % 19 Weder 2007 Gem Cis x NR Krug 2007 Pem Cis x %

20 Chemotherapy for Malignant Mesothelioma I Standard Treatment available Second-Line Treatment more frequently used Personalized Approaches urgently needed Significant Proportion of Elderly Patients (Adaptations needed) Duration of Therapy?

21 Pemetrexed + Cisplatin: Benchmark regimen for Malignant Mesothelioma PC C p Pts RR 41% 17% <0.001 MST 12.1 M 9.3 M TTP 5.7 M 3.9 M Vogelzang, JCO 2003

22 Chemotherapy for Malignant Mesothelioma II Single-Agent therapy? Biologicals? New Drug investigation is feasible in Mesothelioma National/International Cooperation (scheduling priorities) necessary

23 Combined Modality Therapy for MM Radical Surgery Preceded or Followed by Chemotherapy Followed by Radiotherapy Careful Staging/Prognostic Factors Careful Evaluation of Comorbidities/Cardiopulmonary Function Expertise/High-Volume Institutions

24 Radiotherapy for Malignant Mesothelioma Palliative role (drain ports, chest wall) Malignant Mesothelioma: sensitive to radiotherapy Technical Difficulties IMRT

25 Care for Mesothelioma Patients in Australia Urban vs Rural? High-Volume Institution? Multidisciplinary Team Decisions? Accessibility of Expensive Medication? Accessibility of Palliative Care?

26 Research into Cellular Characteristics of Disease HE-stain EGFR; 3+ A: Mesothelioma Standard Microscopy B: Mesothelioma Staining with Antibody

27 New Drugs in MM Biological agents Added to standard treatment Second-Line Treatment International Cooperation Priorities Pharma Industry High-Troughput Screening

28 Research/Education at the ADRI I Patterns of Care for Malignant Mesothelioma in Australia (diagnosis, treatment, rural vs urban etc.) Development of Guidelines for the treatment of Mesothelioma What are psychological consequences of knowledge being exposed to asbestos in the past?

29 Research/Education at the ADRI II Individualisation of treatment: Define upfront which patient is going to respond/benefit from treatment Tissue bank: Find clues for better treatment and prevention New drug development/screening Prevention through Education

30 Thank you!!

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