Mesothelioma in New South Wales

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1 Cancer Institute NSW Monograph Mesothelioma in New South Wales September 2010

2 Bowel Cancer in New South Wales Cancer Institute NSW catalogue number: EM National Library of Australia cataloguing-in-publication data: Pancreatic cancer in New South Wales SHPN (CI) ISBN Key words: Mesothelioma, New South Wales, Australia Suggested citation: Creighton N, Baker D. Mesothelioma in New South Wales. Sydney: Cancer Institute NSW, September Published by the Cancer Institute NSW, September Cancer Institute NSW PO Box 41 Alexandria NSW 1435 Telephone (02) Facsimile (02) E mail Homepage Publications Copyright Cancer Institute NSW September This work is copyright. It may be reproduced in whole or part for study or training purposes subject to the inclusion of acknowledgement of the source. It may not be reproduced for commercial usage or sale. Reproduction for purposes other than those indicated above requires written permission from the Cancer Institute NSW. Cover image: Mesothelioma, cancer of the lungs. X-ray. 00

3 Contents Executive summary 5 1. Introduction 6 2. Identifi cation and management of mesothelioma Anatomy and physiology of mesothelium Pathology Symptoms Diagnosis and staging Management of mesothelioma 8 3. Risk factors and prevention Asbestos Non-asbestos mineral fi bres Other Methods Cases Population estimates Age-standardised rates Survival Projections Data interpretation Incidence and mortality Number of cases and deaths from mesothelioma Trends in degree of spread at diagnosis and survival Degree of spread at diagnosis Survival of mesothelioma Geographic patterns of mesothelioma Incidence and mortality from mesothelioma by accessibility and remoteness Incidence and mortality from mesothelioma by Area Health Service Incidence and mortality from mesothelioma in Australian states and territories International incidence of mesothelioma Mesothelioma in sub-populations Incidence and mortality from mesothelioma by socioeconomic status Incidence and mortality from mesothelioma by country of birth Projections Conclusions 41 Glossary 42 Data tables 45 References Crude incidence and mortality rates from mesothelioma Age-standardised incidence and mortality rates from mesothelioma Age-specifi c incidence rates of mesothelioma Median age at diagnosis and death Incidence of mesothelioma by tumour location 28 1

4 Mesothelioma in New South Wales Tables and fi gures TABLES Table 1 International Mesothelioma Interest Group staging system for diffuse malignant pleural mesothelioma 10 Table 2 Asbestos mines in New South Wales 12 Table 3 Airborne asbestos control levels and required actions 16 Table 4 New cases of mesothelioma in NSW, persons, Table 5 New cases of mesothelioma in NSW, males, Table 6 New cases of mesothelioma in NSW, females, Table 7 Deaths from mesothelioma in NSW, persons, Table 8 Deaths from mesothelioma in NSW, males, Table 9 Deaths from mesothelioma in NSW, females, Table 10 Age-specifi c and age-standardised (ASR) incidence rate (per 100,000) of mesothelioma in NSW, males, Table 11 Age-specifi c and age-standardised (ASR) incidence rate (per 100,000) of mesothelioma in NSW, females, Table 12 Age-specifi c and age-standardised (ASR) mortality rate (per 100,000) from mesothelioma in NSW, males, Table 13 Age-specifi c and age-standardised (ASR) mortality rate (per 100,000) from mesothelioma in NSW, females, Table 14 Cases, crude and age-standardised incidence rates (per 100,000) of mesothelioma by accessibility and remoteness (ARIA+ category), NSW, Table 15 Deaths, crude and age-standardised mortality rates (per 100,000) from mesothelioma by accessibility and remoteness (ARIA+ category), NSW, Table 16 Cases, crude and age-standardised incidence rates (per 100,000) of mesothelioma by Area Health Service, NSW, Table 17 Deaths, crude and age-standardised mortality rates (per 100,000) from mesothelioma by Area Health Service, NSW, FIGURES Figure 1 Apparent asbestos consumption in Australia 13 Figure 2 New cases of mesothelioma, NSW, Figure 3 Number of deaths from mesothelioma, NSW, Figure 4 Crude incidence rate of mesothelioma in NSW, Figure 5 Crude mortality rate from mesothelioma, NSW, Figure 6 Age-standardised incidence rate of mesothelioma, NSW,

5 Figure 7 Age-standardised mortality rate from mesothelioma, NSW, Figure 8 Number of cases of mesothelioma by age group, NSW, Figure 9 Age-specifi c incidence rates of mesothelioma, NSW, Figure 10 Age-specifi c incidence rates of mesothelioma by fi ve-year periods and age groups, NSW, males, Figure 11 Age-specifi c incidence rates of mesothelioma by fi ve-year periods and age groups, NSW, females, Figure 12 Age-specifi c incidence rates of mesothelioma by birth cohort, NSW, males 26 Figure 13 Median age at diagnosis and death from mesothelioma, NSW, males, Figure 14 Median age at diagnosis and death from mesothelioma, NSW, females, Figure 15 Location of tumour, NSW, Figure 16 Degree of spread of mesothelioma at diagnosis, NSW, Figure 17 Relative survival of mesothelioma by gender, NSW, Figure 18 Relative survival of mesothelioma by degree of spread at diagnosis, NSW, Figure 19 Relative survival of mesothelioma by age at diagnosis, NSW, Figure 20 Relative survival of mesothelioma by period of diagnosis, NSW, Figure 21 National and international fi ve-year relative survival (± 95% CI) of mesothelioma 32 Figure 22 Age-standardised incidence and mortality rates (± 95% CI) from mesothelioma by accessibility and remoteness (ARIA+ category), NSW, Figure 23 Age-standardised incidence and mortality rates (± 95% CI) from mesothelioma by Area Health Service, NSW, Figure 24 Age-standardised incidence rates of mesothelioma by state and territory, Figure 25 Age-standardised mortality rates from mesothelioma by state and territory, Figure 26 International age-standardised incidence rates of mesothelioma, males, Figure 27 International age-standardised incidence rates of mesothelioma, females, Figure 28 Age-standardised incidence and mortality rates (± 95% CI) from mesothelioma by socioeconomic disadvantage, NSW, Figure 29 Age-standardised incidence and mortality rates (± 95% CI) from mesothelioma by country of birth, NSW, Figure 30 Age-standardised incidence and mortality rates (± 95% CI) from mesothelioma by region of birth, NSW, Figure 31 Projected number of mesothelioma cases, NSW,

6 Mesothelioma in New South Wales Acknowledgements This report was made possible through the collaboration of many people within the Cancer Institute NSW and the NSW Department of Health. We would particularly like to thank the NSW Central Cancer Registry (NSW CCR) staff for their hard work in processing and coding the data as well as taking the time to explain the processes for coding cancer data. We appreciate the cooperation of statutory notifi ers in the supply of notifi cations and the assistance of medical records personnel, clinicians and pathologists in meeting requests for supplementary information. The NSW CCR is funded by the NSW Department of Health and is managed by the Cancer Institute NSW under an agreement. Mortality details are provided by the NSW Registrar of Births, Deaths and Marriages. Population, demographic and coded cause of death data are provided by the Australian Bureau of Statistics. Population and demographic data were accessed via the Health Outcomes and Information Statistical Toolkit (HOIST). HOIST is a facility that enables data access, analysis and reporting and is operated by the Centre for Epidemiology and Research, Division of Population Health, NSW Department of Health. The authors would like to thank Dr Deborah Yates for reviewing this report. 4

7 Executive summary The annual number of cases of mesothelioma in New South Wales has increased four-fold since Due to its poor survival, a similar pattern is observed for deaths from mesothelioma. Mesothelioma is relatively uncommon, and in 2007 it accounted for 0.6 per cent of all new cases of cancer in New South Wales. Most cases (85%) occur in males. Mesothelioma deaths were 2.4 per cent of all male cancer deaths and it was the 16 th most common cause of cancer mortality in males in Since 1980, the age-standardised incidence rate of mesothelioma has increased signifi cantly in both males and females. In males, the agestandardised incidence rate increased by 5.6 per cent per year until the mid 1990s but has since been relatively stable. In females, the rate of increase has continued at 4.9 per cent per year between 1980 and There is variation in mesothelioma incidence in New South Wales by demographic variables such as geographic location, socioeconomic status and country of birth. The major risk factor for mesothelioma is exposure to airborne asbestos fi bres. The use of all forms of asbestos has been banned since the end of 2003 and some forms of asbestos were banned in the 1980s. However, the average latency period for mesothelioma after fi rst exposure to asbestos is more than 40 years. The number of cases of mesothelioma is projected to increase in New South Wales as the impact of asbestos use in the 1970s and 1980s takes effect. The ban on asbestos does not include asbestos products that were already in use. Implementing safe management and safe work procedures can prevent or minimise exposure to asbestos fi bres and can prevent mesothelioma in the future. Survival of mesothelioma is poor, with 40 per cent of people surviving one year after diagnosis and 4.5 per cent surviving after fi ve years. There has been no signifi cant improvement in survival since the early 1980s. The best prospects are offered by the development of new treatments which improve survival and quality of life for people with mesothelioma. 5

8 Mesothelioma in New South Wales 1. Introduction Mesothelioma is a type of cancer arising from the pleura or peritoneum. It has a poor prognosis, with the median survival time after diagnosis between 9 and 18 months. 1-3 Mesothelioma is primarily associated with exposure to airborne asbestos fi bres. It is uncommon in people that have not been exposed to asbestos. 4-5 Asbestos has been used in many products including asbestos cement, fl oor tiles, chemical and thermal insulation, textiles and friction materials. Asbestos consumption in Australia peaked in the 1970s and declined steeply in the 1980s, following the introduction of regulations on its use and exposure. The use of all forms of asbestos in Australia has been banned since 31 December The ban does not include asbestos containing materials that were already in use. Many asbestos products are still in service. There is typically a 40 year delay between asbestos exposure and the development of mesothelioma. Therefore, the impact of peak asbestos use is still being experienced in New South Wales. Managing asbestos safely is vital to preventing mesothelioma in the future. This report identifi es trends in the incidence and mortality from mesothelioma over the last three decades in New South Wales. It also investigates variations in incidence and mortality by age, geographic areas, socioeconomic status and country of birth. Comparisons are made to the incidence and mortality in other Australian states and territories, and internationally. Survival from mesothelioma by tumour characteristics is also examined. It is envisaged that this information will assist with the planning and provision of services to better diagnose, treat and support people with mesothelioma in New South Wales. 6

9 2. Identifi cation and management of mesothelioma 2.1 Anatomy and physiology of mesothelium Mesothelium lines the cavities of the pleura, pericardium, peritoneum and the tunica vaginalis (surrounding the testes). The mesothelium is a single layer of cells that covers the internal surface of both the parietal and visceral serosal membranes that form these cavities. Most mesothelial cells are squamous with a dense border of microvilli on the luminal surface of the cell. 6 Cuboidal mesothelial cells are predominant in some regions of the pleura and peritoneum and appear to be more metabolically active than the squamous form. 7 The mesothelium is maintained by a slow renewal of cells. 8 The mesothelium provides a barrier for the enclosed organs and a frictionless surface for the movement of apposing organs and tissues. Recently, the mesothelium has also been found to have a wide-ranging role in fl uid and cell transport across the serosal cavity, infl ammatory responses, tissue repair, prevention of adhesion formation and immune responses. 6 Mesothelial cells are dynamic both structurally and functionally in order to maintain the integrity and function of the serosal membrane. 2.2 Pathology Most (~90%) malignant mesotheliomas occur in the pleura. Less than 10 per cent occur in the peritoneum and mesotheliomas of the pericardium and tunica vaginalis are very rare. 9 Mesothelioma typically has a diffuse growth pattern. As the disease progresses, the lesion obliterates the serosal cavity and invades and compresses the underlying organs. 9 The three main histological types of diffuse malignant mesothelioma are epithelioid, fi brous/sarcomatoid and biphasic. The biphasic type has features of epithelioid and sarcomatoid mesothelioma. Epithelioid mesothelioma is the most common type. Approximately fi fty per cent of pleural and 75 per cent of peritoneal mesotheliomas are epithelioid. 9 Biphasic is the next most common type followed by sarcomatoid. 2.3 Symptoms The most common symptoms of pleural mesothelioma are diffi culty breathing and chest pain. 10 These symptoms are usually caused by a pleural effusion or invasion of the chest wall by the cancer The person may also present with a cough or weight loss. Some people have no symptoms and the disease is discovered incidentally. 10 The symptoms of peritoneal mesothelioma are typically abdominal distension and pain, which may be associated with ascites. 10, 13 Bowel obstruction or a palpable mass may present late in the course of the disease. The time between the onset of symptoms and diagnosis of mesothelioma is probably around three months Diagnosis and staging The clinical diagnosis of pleural mesothelioma can be problematic as the symptoms and tumour appearance can be similar to other cancers that invade the pleura. At presentation, a chest X-ray or computerised tomography scan generally shows a pleural effusion and unilateral pleural abnormality. 14 Cytological examination of pleural fl uid often does not provide a defi nitive diagnosis of malignant pleural mesothelioma. Video assisted thoracoscopy or an open pleural biopsy is often needed to get a suffi cient sample for accurate histological and immunohistochemical examination The pathologic diagnosis of mesothelioma is diffi cult due to the similarity of mesothelioma to other malignant and benign conditions. Diagnosing pleural epithelioid malignant mesothelioma often requires exclusion of metastatic carcinomas (most commonly metastatic 7

10 Mesothelioma in New South Wales pulmonary adenocarcinoma) and benign mesothelial hyperplasia Many metastatic cancers can invade the peritoneum and mimic peritoneal mesothelioma. 19 In addition to histological examination, immunohistochemical examinations are required Pathological, clinical and radiological fi ndings need to be considered in the diagnosis of malignant mesothelioma Biomarkers for the diagnosis of malignant mesothelioma currently have limited use in clinical practice. Soluble mesothelin-related protein (SMRP), megakaryocyte potentiating factor (MPF) and osteopontin have shown the most potential as biomarkers However, each has its limitations. SMRP and MPF have good sensitivity and specifi city for epithelioid mesothelioma but are not sensitive to sarcomatoid mesothelioma and have poor sensitivity to biphasic mesothelioma Osteopontin lacks specifi city for mesothelioma A recent prospective study examined the use of SMRP as a screening tool for the early detection of mesothelioma in asbestos-exposed people. The study found that SMRP was unlikely to be useful as a screening tool in asymptomatic people as it had a high false-positive rate. 22 Although this fi nding may change with longer follow-up. SMRP and osteopontin may be useful in a clinical context, particularly in conjunction with other investigations, for diagnostic purposes, prognosis and monitoring response to treatment in mesothelioma patients. 21 Further research and clinical trials are needed before biomarkers gain a routine role in clinical practice. There is a an accepted staging system for diffuse malignant pleural mesothelioma, which was developed by the International Mesothelioma Interest Group (Table 1). 23 This system has been adopted by the American Joint Committee on Cancer (AJCC) and serves as a clinical and pathological staging system. 24 There is not an accepted staging system for peritoneal mesothelioma, although a Peritoneal 3, 25 Cancer Index has been proposed. Computerised tomography (CT) is the primary imaging modality for the evaluation of malignant pleural and peritoneal mesothelioma. 17, 26 For malignant pleural mesothelioma, CT images can indicate invasion of the chest wall or pericardium, spread to thoracic lymph nodes, metastases to the lung and the degree of physical compromise to the lung. 14 However, clinical staging using CT scans often will not provide a reliable assessment of TNM status The assessment of metastases to thoracic lymph nodes, superfi cial invasion of the pericardium, invasion of the diaphragm and endothoracic fascia cannot be determined reliably preoperatively. 16 Thoracoscopy and mediastinoscopy are generally required for accurate TNM staging. 14, 17, 23 The role of endoscopic bronchial ultrasound (EBUS) is still under evaluation. In people that are being considered for surgical resection, magnetic resonance imaging may provide additional information on invasion of the chest wall and diaphragm when CT fi ndings are inconclusive. 27 Positron emission tomography has a role in evaluating extent of 16, 28 disease, providing more accurate information on metastases to lymph nodes and distant sites in some cases. 2.5 Management of mesothelioma Some achievements have been made in the treatment of mesothelioma, but it remains a diffi cult disease to treat and overall survival is poor. Novel therapeutic agents have been suggested as providing better treatment options, however they require evaluation in clinical trials. 1, 29 It is recommended that people with mesothelioma be managed by an experienced multidisciplinary team There are international evidence-based guidelines for the management of mesothelioma and Australian guidelines are under development Resectable disease The main options for the surgical management of malignant pleural mesothelioma are extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). EPP is a radical procedure that involves the en bloc resection of the parietal and visceral pleura, involved lung, diaphragm and pericardium. Low operative mortality for EPP has been achieved in specialised centres, but post-operative morbidity is common. 1, 32 Patients with signifi cant cardiac comorbidities, sarcomatoid histology type, spread to mediastinal lymph nodes and poor performance status are excluded as candidates for EPP as they have a worse prognosis. 1 P/D is a less aggressive surgical approach that 8

11 involves the removal of the parietal pleura, including the pleura over the mediastinum, pericardium and diaphragm, and stripping the visceral pleura to decorticate the lung. There are no evidence-based recommendations derived from randomised clinical trials to indicate the appropriateness of surgery and consequently the use of surgery remains controversial. 1, 17, An international randomised clinical trial studying this issue is currently being planned (the MARS-2 trial) Recurrence after surgery is common and therefore surgery is usually part of a multimodality treatment plan. Mesothelioma is responsive to radiotherapy but its proximity to the heart, lungs, spinal cord, liver, kidney and oesophagus, and also its large surface area and irregular shape impede the delivery of a suffi ciently high radiotherapy dose without causing toxicity. 32, 37 Since the lung is removed during EPP, highdose radiotherapy can subsequently be delivered and good local control may be achieved, but distant recurrences are common New methods of radiotherapy, such as intensity-modulated radiotherapy (IMRT), have not been widely evaluated. 39 Systemic therapy is usually considered in the treatment of resectable mesothelioma since surgery and radiotherapy, alone or in combination, are rarely curative. Combination chemotherapy regimens have a better response rate than single agent chemotherapy. 1, 17 Intrapleural chemotherapy with P/D, often with systemic chemotherapy, has been used but the advantages are unclear and local recurrence remains a problem. 16 It is recommended that adjuvant or neoadjuvant chemotherapy be considered with EPP, 17 although the use of adjuvant chemotherapy may be limited in this context due to its toxicity after EPP. 1 Trimodality therapy (TMT) of resectable mesothelioma, consisting of EPP, high-dose radiotherapy and neoadjuvant or adjuvant combination chemotherapy, has been proposed as providing the best chance of long-term survival in selected patients. 40 But recurrence is a problem, even after completion of a TMT regimen, in reports where this has been evaluated. 39, 41 The impact of TMT on survival and 39, quality of life is unclear and requires assessment in a randomised clinical trial before it can be recommended as the standard therapy Unresectable disease Treatment of unresectable mesothelioma aims to control symptoms, improve quality of life and prolong survival. Most (85 90%) people with mesothelioma present with unresectable disease at diagnosis. 43 A combination of platinum and antifolate based chemotherapy has become the standard of care for people with advanced symptomatic mesothelioma with good performance status. 17, There is currently no standard second-line chemotherapy, but with further studies it may play a role in the management of mesothelioma Palliative care Improving and maintaining quality of life in people with mesothelioma requires addressing physical symptoms and also emotional, psychological, social and spiritual needs. Common symptoms in people with mesothelioma are pain, breathlessness, fatigue, cough and weight loss. Pain from mesothelioma can be complex and specialist pain management or palliative care services should be sought if pain is unresponsive. 29 A combination of opioids and other analgesics is often required to manage pain. 29, 31, 47 Interventional procedures, such as inter-costal nerve blocks and epidurals, may sometimes be useful. 29, 31 Pain due to invasion of the chest wall by the tumour may be alleviated by radiotherapy. 17, 29 Pain control may be further improved by addressing the emotional, psychological, social and spiritual concerns of the person. 31 Pleural effusions are a common cause of breathlessness in people with mesothelioma and can be managed by pleurodesis or palliative pleurectomy. 17, 48 Lung compression and chest wall stiffness are also common causes of breathlessness, with anxiety and weakness also contributing. 31 Medications are usually required to alleviate symptoms of breathlessness but non-drug therapies, such as breathing and relaxation exercises and activity pacing, should also be used. 31 Cough may be relieved by medications, but it is also important to exclude or treat any underlying comorbidities as the cause. 29 Many factors can contribute to fatigue in people with mesothelioma, such as pain, sleep disturbance and emotional distress. It is important to identify and treat the factors that are contributing to fatigue. 49 Energy conservation and distraction techniques can help with the management of fatigue. 49 9

12 Mesothelioma in New South Wales 31, 50 Psychological distress, including depression, anxiety, fear and anger, is common in people with mesothelioma and their carers. Uncontrolled symptoms and medications can contribute to distress. 47 Loss of functioning in work, family and social roles can also cause distress. Patients and their carers can benefi t from a range of supportive services including dieticians, physiotherapists, counsellors, chaplains and support groups. Ensuring that care is coordinated is important in minimising the burden of progressive disease. 31 Table 1 International Mesothelioma Interest Group staging system for diffuse malignant pleural mesothelioma 23 Primary tumour (T) T1a Tumour limited to the ipsilateral parietal pleura, including mediastinal and diaphragmatic pleura. No involvement of the visceral pleura. T1b Tumour involving the ipsilateral parietal pleura, including mediastinal and diaphragmatic pleura. Scattered foci of tumour also involving the visceral pleura. T2 Tumour involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle; confl uent visceral pleural tumour (including the fi ssures) or extension of tumour from visceral pleura into the underlying pulmonary parenchyma. T3 Locally advanced but potentially resectable tumour. Tumour involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic and visceral pleura) with at least one of the following features: involvement of the endothoracic fascia; extension into the mediastinal fat; solitary, completely resectable focus of tumour extending into the soft tissues of the chest wall; nontransmural involvement of the pericardium. T4 Describes locally advanced technically unresectable tumour. Tumour involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic and visceral) with at least one of the following: diffuse extension of multifocal masses of tumour in the chest wall, with or without associated rib destruction; direct transdiaphragmatic extension of tumour into the peritoneum; direct extension of tumour to the contralateral pleura; direct extension of tumour to one or more mediastinal organs; direct extension of tumour into the spine; tumour extending through to the internal surface of the pericardium with or without a pericardial effusion, or tumour involving the myocardium. Regional lymph nodes (N) NC No regional lymph node metastasis N1 Metastases in the ipsilateral bronchopulmonary or hilar lymph nodes N2 Metastases in the subcarinal or the ipsilateral mediastinal lymph nodes, including the ipsilateral internal mammary nodes N3 Metastases in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral supraclavicular lymph nodes NX Regional lymph node cannot be assessed Distant metastasis (M) M0 No distant metastases M1 Distant metastases MX Presence of distant metastases cannot be assessed Stage TNM Stage Ia T1aN0M0 Stage Ib T1bN0M0 Stage II T2N0M0 Stage III Any T3M0 Any N1M0 Any N2M0 Stage IV Any T4 Any N3 Any M1 10

13 3. Risk factors and prevention 3.1 Asbestos Risks from asbestos The term asbestos refers to a group of naturally occurring fi brous silicate minerals. There are two main types of asbestos: amphibole and serpentine asbestos. Crocidolite (blue asbestos), amosite (brown asbestos) and the less common anthophyllite and tremolite are amphiboles and chrysotile (white asbestos) is serpentine. The association between asbestos and mesothelioma was fi rst established in 1960 in a study on the incidence of mesothelioma in people working and living near a crocidolite asbestos mine in Cape Province, South Africa. 51 Amphibole asbestos types are more potent carcinogens for mesothelioma compared to chrysotile. The difference in potency between chrysotile and amphibole asbestos is estimated to be around one hundred times or more, with crocidolite around fi ve times more potent than amosite The ability of pure chrysotile asbestos to cause mesothelioma is still debated, with the suggestion that the elevated risk of mesothelioma in chrysotile-exposed workers is due to amphibole asbestos fi bres which often occur naturally in chrysotile asbestos However, chrysotile has now been banned in Australia and in many other countries The toxicity of asbestos fi bres is related to fi bre diameter, fi bre length and biopersistence. The small diameter of asbestos fi bres enables the penetration and deposition of inhaled fi bres beyond the ciliated airways of the lungs. 59 A small proportion of deposited fi bres move from the lung into the pleural cavity. The impedance of normal clearance mechanisms from the pleural cavity can result in the fi bres causing chronic infl ammation, cytotoxicity and genotoxicity to the mesothelial cells, which may lead to carcinogensis The translocation of fi bres from the pleural cavity to the peritoneal cavity is thought to be responsible for peritoneal mesotheliomas. 59, Long (>8 μm) and thin (<0.25 μm) fi bres are generally thought to be the most carcinogenic for mesothelioma, 53, 59 but short asbestos fi bres have also been implicated in mesothelioma development. 53, The carcinogenicity of short fi bres cannot be ruled out and asbestos fi bres of all 53, 64 length may potentially contribute to the development of mesothelioma. The biopersistence of asbestos fi bres is an important factor in mesothelioma carcinogenesis. Greater biopersistence increases the likelihood that a fi bre will reach the pleura or peritoneum and cause sustained damage to the mesothelial cells. 59 Biopersistence is related to the durability of the fi bres and their ability to be handled by the normal physiological clearance mechanisms for particles. Dissolution and breakage of asbestos fi bres can decrease biopersistence. 59, 65 The greater carcinogenicity for mesothelioma of amphibole compared to chrysotile asbestos is likely due to the greater biopersistence of amphiboles. 53 Amphibole asbestos fi bres are eliminated from the lungs very slowly (over many years) whereas chrysotile asbestos fi bres are eliminated more rapidly The chemical composition of amphibole asbestos fi bres may also increase their carcinogenicity. Amphiboles generally have a higher iron content, which may increase oxidative damage to the mesothelial cells from the production of reactive oxygen species. 68 As well as asbestos fi bre characteristics, the exposure characteristics and time since exposure greatly affect mesothelioma risk. There is a dose-response relationship between cumulative asbestos exposure and risk of mesothelioma. 52, 69 Cumulative exposure is a product of the exposure intensity (fi bre concentration in the air) and exposure duration. This means that short-term but intense exposures can increase the risk of mesothelioma. 52 The risk of mesothelioma is very low in the fi rst 20 years after exposure to asbestos but increases exponentially (to the power of 3 4) with time. 52, 65, 70 The average latency period for mesothelioma after fi rst exposure to asbestos is more than 40 years

14 Mesothelioma in New South Wales Even in cohorts with high exposure to asbestos, most people will die from causes other than mesothelioma. 55, Estimates of mesothelioma mortality in a cohort are affected by asbestos fi bre type, exposure characteristics and also the length of follow-up. Mesothelioma deaths were 10 per cent of all deaths in a cohort of crocidolite miners and millers, 75 but were generally less than one per cent of deaths in cohorts of chrysotile-exposed workers. 55 However, asbestos exposure also increases mortality from lung cancer and 52, asbestosis. Smoking does not appear to increase mortality from mesothelioma, but it increases the risk of lung cancer and asbestosis in asbestosexposed workers. 77, There is a synergistic relationship between smoking, asbestos exposure and the risk of lung cancer. 79 People who smoke and have worked with asbestos have a greatly increased risk of lung cancer. The number of lung cancer deaths attributable to asbestos is affected by changes in smoking prevalence. It is estimated that there are up to two deaths from lung cancer for every death from mesothelioma , 79 Quitting smoking can decrease the risk of lung cancer in asbestos-exposed people Asbestos use New South Wales was the fi rst state in Australia to mine asbestos at Jones Creek between 1880 and The commercially mined asbestos deposits in New South Wales are listed in Table 2. There are also other small deposits and occurrences of asbestos in New South Wales that were not commercially exploited. The largest production of asbestos in New South Wales and Australia was from the Woodsreef mine, which produced 550,000 tonnes of chrysotile asbestos between 1972 and New South Wales produced approximately three quarters of the total Australian asbestos production. 84 Table 2 Asbestos mines in New South Wales. From Hendrickx, Name Asbestos type Production (tonnes) Woodsreef Asbestos Mine Chrysotile 550,000 Baryulgil Asbestos Mine Chrysotile 19,432 Byng/Lewis Ponds Asbestos Tremolite 338 Jones Creek Asbestos Mine Tremolite 72 Rockley Asbestos Mine Tremolite 50 Red Hill/Rockwell Paddock Chrysotile 8 Large amounts of asbestos fi bre and asbestos products were imported into Australia. The amount of chrysotile asbestos imported was around double the amount produced locally and half as much crocidolite was imported as was produced in Australia. 4 Chrysotile is the most common type of asbestos. It was 79 per cent of Australian asbestos production and 61 per cent of the total asbestos imports into Australia. 4 Asbestos consumption in Australia was highest in the 1970s with approximately 700,000 tonnes consumed (Figure 1). There are no data available on asbestos consumption by state, but consumption is estimated to be proportional to population size, with additional weighting to New South Wales and Victoria as the states with the most industrial activity

15 Figure 1 Apparent asbestos consumption in Australia. From Leigh et al., , ,000 Tonnes of asbestos 600, , , , , ,000 0 Year The thermal and chemical insulation properties and also the strength and durability of asbestos products resulted in their widespread use. Common uses of asbestos include: Asbestos cement sheets used for cladding and roofi ng, sewage and water pipes, guttering, switchboards, casings for electrical and telecommunication services Lagging on pipes, boilers, furnaces and ducting in buildings, factories and ships Fire-rated doors Textile products cloth and rope for thermal and chemical insulation Construction materials vinyl fl oor tiles and underlay, paints, caulking compounds, sealants, damp-proofi ng Friction materials such as brake and clutch linings Sprayed ( limpet ) asbestos on structural beams of buildings and the underside of roofs for fi re protection. The asbestos cement manufacturing industry was the largest consumer of asbestos in Australia, using over 60 per cent of all domestic production and 90 per cent of all asbestos fi bre consumption. 4 Crocidolite, amosite and chrysotile were used in asbestos cement between 1940 to the late 1960s when crocidolite was phased out. Amosite was phased out in asbestos cement in the early 1980s and chrysotile was used until about Most asbestos cement was used for home cladding (the fi bro house) and in sewage and water pipes. Approximately 70,000 asbestos cement houses were built in New South Wales between 1940 and 1954, with Australia having the highest per capita consumption of asbestos cement in the western world during this time. 4 13

16 Mesothelioma in New South Wales The widespread use of asbestos products has resulted in workers in many occupations being exposed. There are four main areas where workers have been exposed: Primary production of asbestos - mine and mill workers, workers involved with asbestos transport domestically and at wharves for export Manufacturing of asbestos products workers at factories producing asbestos cement, brake linings, textiles, etc Installing and using asbestos products carpenters, plumbers, electricians, labourers, fi tters, shipping workers, power station workers, boiler makers, rail workers, etc Working with in situ asbestos products workers undertaking maintenance, renovation or demolition work on buildings, plant or equipment that contain asbestos products. In New South Wales, occupation information for mesothelioma cases is collected by the Dust Diseases Board (DDB) for persons that have made successful claims for compensation due to occupational asbestos exposure. Relatively few cases in New South Wales have been in the mining industry, 73 which refl ects the relatively small amount of amphibole asbestos mined. There has been a change over time in the type of industry where asbestos exposure occurred for cases on the DDB register. Cases diagnosed in the 1970s and early 1980s were mainly exposed in the manufacturing industry. Since the late 1990s, the construction industry has been the most common exposure to asbestos for mesothelioma cases (around 40% of cases). 73 For mesothelioma cases on the DDB register diagnosed between 2000 and 2004, the most common occupation categories for asbestos exposure were construction trades workers (31%), automotive and engineering trades workers (17%), factory workers (11%), construction and mining labourers (9%) and machine and stationary plant operators (7%). 73 For female mesothelioma cases on the DDB register diagnosed between 1972 and 2004, the most common occupational exposures were steam press operators (15%), process workers (14%), clerical workers (14%) and textile machine operators (12%) Asbestos regulations The use of all forms of asbestos in Australia ended on 31 December 2003 when regulations banning the use of chrysotile asbestos and confi rming earlier bans on amphibole asbestos came into force. 58 All forms of amphibole asbestos were banned in Australia in the mid 1980s. The ban does not include asbestos containing materials that were already in use. In situ asbestos products that are in good condition and are not disturbed pose minimal risk to health. 58 When an asbestos product deteriorates or is no longer fi t for use, it must be replaced with a non-asbestos product. It is illegal to re-use or install asbestos products. 85 The large amounts of asbestos products that are still in service mean that there is the potential to disturb asbestos containing materials during maintenance, repair, renovation or demolition work on buildings, plant and equipment. It is essential that asbestos containing materials are managed appropriately to minimise exposure to airborne fi bres. Two codes of practice were developed by the National Occupational Health and Safety Commission which detail the requirements for the management and control of in situ asbestos and the removal of asbestos containing materials. These codes have been adopted in New South Wales occupational health and safety legislation. A guide on Working with Asbestos has been prepared by WorkCover New South Wales and provides information on the regulations and safe work procedures (available at 86 Asbestos is defi ned as friable or non-friable (bonded) under the legislation. Friable asbestos is any asbestos containing material which, when dry, can be crumbled, pulverised or turned to powder by hand. Friable asbestos includes sprayed ( limpet ) asbestos, cloth, rope, millboard and lagging. Bonded asbestos is any asbestos containing material in which the asbestos fi bres are bound in a matrix such that it cannot be crushed by hand when dry. Bonded asbestos includes asbestos cement sheeting, asbestos cement pipes and brake and clutch 14

17 linings. Bonded asbestos that has been subjected to weathering or damage may meet the defi nition of friable asbestos Working with or disturbing friable asbestos has a much higher potential to release asbestos fi bres into the air compared to bonded asbestos. The three main components of the management of asbestos in the workplace are the identifi cation of asbestos, risk assessment of asbestos and the implementation of control measures to prevent, as far as practicable, the generation of airborne asbestos fi bres and exposure to airborne asbestos fi bres. 85 Workplaces containing asbestos are required to have an asbestos register which details the components of the asbestos management plan The register should specify the location of all asbestos (including inaccessible areas that can be presumed to contain asbestos), identify the type of asbestos (eg friable, non-friable, asbestos cement sheet, lagging, gaskets, etc) and state the condition of the asbestos containing material. The risk assessment of identifi ed and presumed asbestos should consider the condition of the asbestos containing material, the likelihood of exposure and whether the nature or location of any work is likely to disturb the material. 85 The ultimate goal is to eliminate asbestos from the workplace. Therefore, consideration should be given to the removal of asbestos containing materials during renovation, refurbishment and maintenance work, rather than to other control measures (such as encapsulation or sealing). 85 If asbestos material is to be maintained in the workplace, it should be labelled appropriately. The risk assessment should also determine periods for re-inspection of asbestos containing materials. The fi ndings of the risk assessment and the recommended control measures should be documented in the asbestos register. There are various control measures that should be used when conducting work that may disturb asbestos Firstly, all workers and contractors should be aware of the presence of asbestos and have suffi cient training and skills to undertake work that may disturb asbestos containing materials. Barriers and signs around the area of work should be established to restrict entry to the area. Methods that minimise the generation of airborne asbestos fi bres should be used. These include using non-powered hand tools and dampening the material with wetting agents. Under New South Wales legislation, water blasting and other high pressure processes are prohibited on asbestos containing materials. 86 The need for personal protective equipment, including the required level of respirator, should be determined. Decontamination of the work area and equipment and also personal decontamination should be performed. Examples of procedures for working safely with asbestos can be found in the WorkCover NSW guide and in the Code of Practice Removing asbestos containing materials can potentially cause higher exposures to airborne asbestos fi bres than leaving the material in place. 87 In New South Wales, a friable asbestos licence is required to remove, repair or disturb any amount of friable asbestos. Bonded asbestos material that has deteriorated and meets the defi nition of friable asbestos must be handled by a contractor with a friable asbestos licence The removal of more than 10 square metres of bonded asbestos (such as asbestos cement sheets) must be undertaken by a person with a bonded asbestos licence. 86 Persons with a bonded or friable asbestos licence can remove any amount of bonded asbestos cement. Appropriate work permits and notifi cations must be lodged with WorkCover NSW prior to the work. 86 All forms of asbestos waste must be disposed of in a manner approved by the NSW Department of Environment and Climate Change at a facility licensed to accept asbestos waste. When working with asbestos, the national exposure standard must not be exceeded under any circumstances. The national exposure standard for all forms of asbestos is 0.1 fi bres per millilitre of air (fi bres/ml). 88 The exposure standards for asbestos have become increasingly stringent since they were fi rst adopted in Australia in the 1970s. In the early 1980s, the exposure standard was 0.1 fi bres/ ml for crocidolite and 1 fi bres/ml for amosite and chrysotile. The exposure standard was reduced to 0.1 fi bres/ml for amosite in the late 1980s and for chrysotile in July Prior to stringent exposure standards, airborne fi bre concentrations were estimated to have reached 150 fi bres/ml at an asbestos cement plant and 600 fi bres/ml at a Western Australian crocidolite asbestos mine. 58, 89 The closure of the Woodsreef asbestos mine in New South Wales in 1983 was due to the inability to meet dust control requirements. 89 The aim of asbestos control is to eliminate or to otherwise to keep exposure to airborne asbestos fi bres as low as reasonably practicable below the national exposure standard Accordingly, the National Code of Practice also specifi es control levels for airborne asbestos which are set below the national exposure standard (Table 3). 87 If a control level is exceeded it indicates that there is the need to review 15

18 Mesothelioma in New South Wales control measures for airborne asbestos fi bre generation or to stop work and identify the cause of airborne fi bre generation. Control levels are occupational hygiene best practice and are not health-based standards. 85, 87 They indicate the effectiveness and adequacy of control measures used during asbestos work. Table 3 Airborne asbestos control levels and required actions Control level Action (airborne asbestos fi bres/ml) < 0.01 Continue with control measures 0.01 to 0.02 Review control measures 0.02 Stop removal work and fi nd the cause A recent study by Safe Work Australia examined asbestos exposure and compliance with occupational health and safety requirements by construction and maintenance workers (electricians, plumbers, carpenters and painters). 90 These workers are likely to undertake work that may disturb asbestos containing materials. Although there was a high level of awareness of the health risks of asbestos fi bres and the mechanisms that generate airborne asbestos fi bres, this was not matched with the ability to recognise asbestos containing material and apply safe work methods. The study recommended that there needs to be greater asbestos awareness and more trade and job specifi c guidance for identifying asbestos containing materials and practical examples of working with asbestos. The study also highlighted the need to ensure that asbestos registers are kept accurately up-to-date and that asbestos containing materials are appropriately labelled Non-occupational asbestos exposure The majority of mesothelioma cases have an occupational exposure to asbestos. It is diffi cult to estimate the percentage of mesothelioma cases due to non-occupational asbestos exposures People may have been unknowingly exposed to asbestos at work and may have both occupational and non-occupational exposures. Estimates of the percentage of cases due to non-occupational asbestos vary in different populations and by gender, but may be around 20 per cent. 91 Non-occupational exposures may be high in some circumstances, but for the general population are much lower (by several orders of magnitude) than past occupational exposures in high risk industries. 5, 92 91, Similar to occupational exposures, the magnitude of risk appears to depend largely on the amount of exposure and fi bre type. Domestic asbestos exposure occurred in the households of asbestos workers from fi bres brought home on their clothes. Studies have found an increased risk of mesothelioma for women living with asbestos workers In one study, the risk of mesothelioma increased, but not statistically signifi cantly, for women who washed the clothes of or lived with crocidolite asbestos miners and millers. 94 Nearby residents of asbestos mines and factories have been found to have an increased risk of mesothelioma due to environmental asbestos 93, exposure. Domestic exposure to tremolite asbestos in areas of Turkey, Greece and New Caledonia, where tremolite-bearing rocks were used to make white-wash for the inside of houses, caused an increased incidence of mesothelioma. 99 Environmental exposure to tremolite fi bres suspended in the air from the rock and soil may also have contributed to the increased risk of mesothelioma. Asbestos containing materials in buildings pose minimal risk to health if the materials are in good condition and are not disturbed. 58 Asbestos materials in poor condition and the uncontrolled disturbance of asbestos containing materials may release quantities of asbestos fi bres into the air that are a risk to health. 5, 58 The release of asbestos fi bres from the ageing and weathering of non-friable asbestos building materials (such as asbestos cement sheets) is very low

19 A guide for homeowners of fi bro houses in New South Wales can be found at bro (accessed June 2010). It is not possible to determine visually if fi bro cladding contains asbestos. The most accurate way to determine if fi bro cladding contains asbestos is to have it tested by a licensed asbestos removalist. There is also a factsheet on asbestos and health risks from the NSW Department of Health at (accessed June 2010). 3.2 Non-asbestos mineral fi bres Exposure to erionite, a fi brous non-asbestiform mineral, is associated with a high risk of mesothelioma An epidemic of mesothelioma linked to erionite exposure was identifi ed in three isolated villages in Turkey. Residents of the village had chronic exposure to erionite. They were exposed to erionite while cutting the local volcanic rock, which was used for construction, and they received exposure from the living quarters, barns and surrounding environment Other People that received Thorotrast have an increased risk of mesothelioma. 103 Thorotrast was a radioactive contrast medium used in radiography from the late 1920s until the early 1950s. A number of case reports have described mesothelioma in patients who had thoracic radiotherapy for different cancers, but this association was not confi rmed in a later controlled study. 104 Simian virus 40 (SV40) has been proposed as a cofactor with asbestos in the pathogenesis of mesothelioma It is suggested that mesothelial cells infected with SV40 are more susceptible to malignant transformation in the presence of asbestos. However, this issue remains in dispute There is evidence that a genetic predisposition can make people more susceptible to mesothelioma carcinogenesis by asbestos and erionite fi bres The genetic susceptibility is likely to be due to a number of genes which are starting to be identifi ed

20 Mesothelioma in New South Wales 4. Methods 4.1 Cases Cases were selected from the New South Wales Central Cancer Registry (NSW CCR) based on the International Classifi cation of Diseases for Oncology 3rd edition (ICD-O-3) morphology codes for malignant mesothelioma ( ). Notifi cation of invasive cancer cases to the NSW CCR by public and private hospitals, pathology laboratories, radiation oncology departments, outpatient departments, day procedure centres and nursing homes has been a statutory requirement in New South Wales since Data in this report were extracted from the NSW CCR as of June 2009 and include cases diagnosed to the end of The number of cases of mesothelioma in the 1970s may be underreported on the NSW CCR. Underreporting of mesothelioma has been found in the United Kingdom The clinical and pathological similarity of mesothelioma to other cancers (section 2.4) may have resulted in the under-diagnosis of mesothelioma cases. Particularly prior to the 1980s, mesothelioma was rare and may not have been considered as a diagnosis, especially if a history of working with asbestos was not disclosed. 74, 118 The lack of diagnostic criteria for mesothelioma also made pathological diagnosis diffi cult in the 1970s. 118 Even with the improvement in diagnostic methods in recent years, diagnosing mesothelioma remains challenging. Recent work on modelling mesothelioma incidence and mortality in New South Wales and the United Kingdom considered that there has been a fi ve per cent decrease in missing cases per year until 1997, by which time case ascertainment is assumed to be essentially complete (98%). 117, 119 Mesothelioma case numbers on the NSW CCR are not likely to be substantially affected by a diagnostic trend from the early 1980s onwards Cancer Incidence Cancer incidence refers to new cases diagnosed in a given population during a specifi ed period. The incidence data in this report are based on mesothelioma cases diagnosed from 1972 to 2007 in New South Wales residents Cancer Mortality Cancer mortality refers to deaths from cancer in a given population occurring in a specifi ed period. These cancers may have been diagnosed during or before the period. The mortality data in this report are based on persons who were diagnosed with mesothelioma while residing in New South Wales and died of that cancer between 1972 and The number of mesothelioma deaths in the 1970s may be affected by the under-diagnosis of mesothelioma cases (section 4.1). Cases that died from mesothelioma after migrating to other Australian states and territories are included in this report. Cases that died overseas are lost to follow-up. People that died from mesothelioma in New South Wales but were not New South Wales residents at the time of diagnosis are not included in this report. There may be differences in the number of mesothelioma deaths reported from the NSW CCR compared to reports published using mortality data from the Australian Bureau of Statistics (ABS) due several factors. The ABS codes cause of death from death certifi cates from the Registrars of Births, Deaths and Marriages of all Australian states and territories. Coded cause of death information is provided to the NSW CCR by the ABS. As well as death certifi cate information, NSW CCR coders assign a cause of death using information from pathology reports and other cancer notifi cations which may result in a different cause of death being assigned. ABS mortality data are reported by the usual residence at death, whereas this report only includes mesothelioma deaths of cases that were diagnosed in New South Wales residents. ABS mortality data are often reported by year of death registration, rather than year of death. 18

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