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Malignant mesothelioma in Australia 2015:Current incidence and asbestos exposure trends

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Australia is known to have had the highest per-capita asbestos consumption level of any nation, reaching a peak in the 1970s. Although crocidolite was effectively banned in the late 1960s, and amosite use ceased in the mid 1980s, a complete asbestos ban was not implemented until 2003. This resulted in an epidemic of asbestos-related disease, which has only now reached its peak. Between 1982 and 2011, 13,036 individuals were newly diagnosed with malignant mesothelioma, with 690 diagnosed in 2011. A further 778 cases were identified between 1945 and 1981 from retrospective searches and the first 2 years of the Australian Mesothelioma Program. The age-standardized malignant mesothelioma incidence rate has leveled off in the last 10 years (2.8 per 100,000 in 2011). There has been a marked increase over time in the age-specific incidence rates for individuals aged 75 years or older. Data from the current Australian Mesothelioma Registry on asbestos exposure history in Australia is available for 449 subjects diagnosed between July 1, 2010, and April 1, 2015. This asbestos exposure history data show that 60% (n = 268) of cases had probable or possible occupational asbestos exposure, with trade-based jobs being the most frequent sources of occupational asbestos exposure. In addition, out of the 449 cases, 377 were recorded as having probable or possible nonoccupational asbestos exposure. Continuous vigilance toward changes over time in the settings in which people are exposed to asbestos and in the descriptive epidemiology of malignant mesothelioma is recommended to enable a comprehensive understanding of the current and future impact of asbestos-related diseases in Australia.
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Malignant mesothelioma in Australia 2015:
Current incidence and asbestos exposure trends
Matthew J. Soeberg, James Leigh & Nico van Zandwijk
To cite this article: Matthew J. Soeberg, James Leigh & Nico van Zandwijk (2016) Malignant
mesothelioma in Australia 2015: Current incidence and asbestos exposure trends, Journal of
Toxicology and Environmental Health, Part B, 19:5-6, 173-189
To link to this article: http://dx.doi.org/10.1080/10937404.2016.1194254
Published online: 05 Oct 2016.
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Malignant mesothelioma in Australia 2015: Current incidence and asbestos
exposure trends
Matthew J. Soeberg, James Leigh, and Nico van Zandwijk
Asbestos Diseases Research Institute, University of Sydney, Concord, New South Wales, Australia
ABSTRACT
Australia is known to have had the highest per-capita asbestos consumption level of any nation,
reaching a peak in the 1970s. Although crocidolite was effectively banned in the late 1960s, and
amosite use ceased in the mid 1980s, a complete asbestos ban was not implemented until 2003.
This resulted in an epidemic of asbestos-related disease, which has only now reached its peak.
Between 1982 and 2011, 13,036 individuals were newly diagnosed with malignant mesothelioma,
with 690 diagnosed in 2011. A further 778 cases were identified between 1945 and 1981 from
retrospective searches and the first 2 years of the Australian Mesothelioma Program. The age-
standardized malignant mesothelioma incidence rate has leveled off in the last 10 years (2.8 per
100,000 in 2011). There has been a marked increase over time in the age-specific incidence rates
for individuals aged 75 years or older. Data from the current Australian Mesothelioma Registry on
asbestos exposure history in Australia is available for 449 subjects diagnosed between July 1,
2010, and April 1, 2015. This asbestos exposure history data show that 60% (n= 268) of cases had
probable or possible occupational asbestos exposure, with trade-based jobs being the most
frequent sources of occupational asbestos exposure. In addition, out of the 449 cases, 377 were
recorded as having probable or possible nonoccupational asbestos exposure. Continuous vigi-
lance toward changes over time in the settings in which people are exposed to asbestos and in
the descriptive epidemiology of malignant mesothelioma is recommended to enable a compre-
hensive understanding of the current and future impact of asbestos-related diseases in Australia.
Australia is one of a number of high-income countries
considered to be a sentinel site for observing over time
the adverse human health, environmental, economic,
and social effects associated with high levels of prior
asbestos consumption. This is due to the fact that
Australia had the worldshighestper-capitaasbestos
consumption rate in the 1950s, primarily from
mining, use of asbestos in construction materials,
and also importation of asbestos-containing products
(Henderson and Leigh 2011;LeighandDriscoll2003).
Asbestos consumption in Australia peaked in the
1970s at 704,425 metric tonnes (19701979 aggregate)
(Leigh et al. 2002). Between 1880 and 1889 approxi-
mately 47 tonnes of amphiboles was mined at Jones
Creek, near Gundagai, New South Wales, and between
1890 and 1899 about 35 tonnes of chrysotile was
mined at AndersonsCreek,Tasmania.South
Australia was the first state to mine crocidolite, at
Robertstown in 1916.
Over the 20th century there was a gradual rise in
asbestos production, with more chrysotile than
amphiboles mined until 1939. With the commence-
ment of mining at Wittenoom, Western Australia, in
1937, crocidolite dominated production, until final
closure in 1966. New South Wales, the first state to
mine asbestos, also produced the largest tonnages of
chrysotile (until 1983), as well as smaller quantities
of amphiboles (until 1949). With the closing of the
crocidolite mine at Wittenoom in 1966, Australian
asbestos production declined to a pre-1952 level.
Australian asbestos (crocidolite and chrysotile) was
exported to the USA, Japan, UK and Europe. In
particular, Wittenoom crocidolite was exported to
the United States and Europe. The export process
itself, bagging, transport, and wharf labor, enhanced
exposure. Exports declined from 1967. Imports of
chrysotile also started to decline. The earliest records
of asbestos imports date from 1929. The main
CONTACT Dr. Matthew J. Soeberg matthew.soeberg@sydney.edu.au Asbestos Diseases Research Institute (ADRI), Bernie Banton Centre, Gate 3,
Hospital Road, Concord Hospital, Concord, NSW 2139, Australia.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B
2016, VOL. 19, NOS. 56, 173189
http://dx.doi.org/10.1080/10937404.2016.1194254
© 2016 Taylor & Francis
sources of raw asbestos imports were Canada (chry-
sotile) and South Africa (crocidolite and amosite).
Approximately twice as much chrysotile was
imported as was mined and half as much crocidolite
was imported as was mined. After Wittenoom was
closed, 122 tonnes of crocidolite were mined in
South Australia. In New South Wales, the chrysotile
mine at Baryulgil continued production. In 1971 the
chrysotile deposits at Woodsreef near Barraba, New
South Wales, began to be exploited and exports of
asbestos fiber expanded as production was elevated.
This operation was open-cast with dry milling.
Australian production of asbestos fiber decreased in
1981 because of the fall in world demand for asbestos
and increased operating costs at the Woodsreef
mine. This mine ceased production in 1983 when
the dry milling plant could not meet dust control
regulations.
In addition to imports of asbestos fiber, Australia
also imported many manufactured asbestos pro-
ducts, including asbestos cement articles, asbestos
yarn, cord and fabric, asbestos joint and millboard,
asbestos friction materials, and gaskets. The main
sources of supply were the United Kingdom, the
United States, the Federal Republic of Germany,
and Japan. In Australia more than 60% of all produc-
tion and 90%of all consumption of asbestos fiber was
by the asbestos cement manufacturing industry.
From about 1940 to the late 1960s all three types of
asbestos were used in this industry, with crocidolite
then being phased out. Amosite use in this industry
continued until about 1983.Chrysotile was used until
about 1987. Much of this industry output remains in
service today in the form of fibrohouses and water
and sewerage piping. By 1954 Australia was number
4intheworldingrossconsumptionofasbestos
cement products, after the United States, the Uited
Kingdom and France, and clearly first on a per-capita
basis. After World War II to 1954, 70,000 asbestos
cement houses were built in the state of New South
Wales alone (52% of all houses built). In Australia, as
awhole,untilthe1960s,25%ofallnewhousingwas
clad in asbestos cement.
Chrysotile use continued in friction products,
sealing gaskets, and adhesives until 2003, with a
complete ban on all importation and use of asbestos
across Australia occurring in 2003 (Jamrozik, de
Klerk, and Musk 2011;Leighetal.2002). However,
due to the long latency period between asbestos
exposure and asbestos-related disease, ranging
between 10 and 50 or more years (Linton et al.
2012), these deleterious human health effects are
still present.
There are nonmalignant and malignant asbestos-
related diseases. The first group includes pleural pla-
ques, diffuse pleural thickening, and asbestosis.
Asbestos-related lung cancer and malignant mesothe-
lioma are the two most important malignant condi-
tions elicited by asbestos (Jamrozik, de Klerk, and
Musk 2011). Malignant mesothelioma is the most
commonly measured epidemiological marker of
asbestos-related disease burden in Australia due to
its strong epidemiological associations with exposure
to airborne asbestos fibers, as noted by International
Agency for Research on Cancer (IARC 2012)aswellas
the ability to monitor disease trends using high-quality
Table 1. Trade-specific exposure assessment for people diagnosed with malignant mesothelioma, Australia, July 1, 2010, to April 1,
2015, according to the probability of asbestos exposure. Note. Data extracted from the Australian Mesothelioma Registry report
published in 2015.
Job title
Assessed probability of exposure
Probable asbestos exposure
High Medium Low Possible asbestos exposure Unlikely asbestos exposure
Construction (carpenter, joiner,
builder, bricklayers, etc.)
88 3 10
Other metal and mechanical
trades (including fitters, turners,
machinists)
48 2 6 11
Other (not specified) 27 1 4 20
Electrician 25 4 7
Boilermaker, welder 21
Plumber 18 1 1 2
Engineer 5 2 3
Telecommunications technician 2 2 5
174 M. J. SOEBERG ET AL.
population-level data. Malignant mesothelioma, most
frequently located in the pleura (more than 90%), has
arapidonsetofmortalityinthefirstyearfollowing
diagnosis. Median survival for malignant mesothe-
lioma has been estimated to range between 9 and
12 mo from the time of diagnosis to death from any
cause (Kao et al. 2010;Lintonetal.2012;2014).
High-quality international data on age-standar-
dized cancer incidence rates, using an international
age distribution,demonstrated that Australia andthe
United Kingdom have significantly higher incidence
rates of malignant mesothelioma compared to other
parts of the world (Forman et al. 2014). For example
during 20032007, Australias male age-standar-
dized malignant mesothelioma incidence rates ran-
ged between 2.5 and 3.1 per 100,000 person-years. In
almost all other countries, the male age-standardized
incidence rates were approximately 1 per 100,000 or
below. Across all countries, female age-standardized
incidence rates were generally below 1 per 100,000,
reflecting gender differences in asbestos exposure.
At the population level, information regarding the
disease burden of malignant mesothelioma in
Australiaand all other malignant diseaseis
recorded through cancer registration at the subna-
tional level, where these records are then aggregated
into a national cancer database referred to as the
Australian Cancer Database. Australia has also
made significant investment in developing a malig-
nant mesothelioma surveillance system that records
incident cases of malignant mesothelioma and,
where possible, asbestos exposure histories. These
surveillance systems included integration of high-
quality population-based cancer registration data
with the collection of asbestos exposure histories
from those newly diagnosed with malignant
mesothelioma. While these surveillance systems
have not been continuous over time, they provide
useful data for identifying particular subpopulation
groups who are more at risk of developing malignant
mesothelioma.
In this paper, we aim to present up-to-date
information regarding the descriptive epidemiol-
ogy of malignant mesothelioma in Australia and
an overview of asbestos exposure data collected
through the current and previous Australian
Mesothelioma Registry. In particular, the inci-
dence (occurrence of new cases of malignant
mesothelioma), measured as both a count and a
rate measure by age group, gender, and jurisdic-
tion, will be examined. These data have been
extracted from routine reporting from both the
Australian Cancer Database and the Australian
Mesothelioma Registry, where aggregate data on
incidence are available. A summary of malignant
mesothelioma data published by the Australian
Institute of Health and Welfare of relative survival,
a population-based measured that accounts for all
causes of death, is also presented. The most
recently available data on asbestos exposure for
individuals diagnosed after July 1, 2010, from the
Australian Mesothelioma Registry are provided
and these data are supplemented with other asbes-
tos exposure reports in Australia.
Population-based data sources to measure
malignant mesothelioma
Incidence
There are two primary data sources for measuring
malignant mesothelioma incidence in Australia. The
first data source is the Australian Cancer Database.
The Australian Cancer Database is a data collection
of all primary, malignant cancers diagnosed in
Australia since 1982, where data are compiled at
the Australian Institute of Health and Welfare from
cancer data provided by the eight Australian statu-
tory population-based state and territory cancer
registries. Information about a cancer diagnosis in
Australia is received from various sources, including
hospitals, pathology labs, radiotherapy centers, and
birth, death, and marriage registries. Currently, the
Australian Cancer Database is considered complete
for all incident cancers diagnosed during 19822009,
although preliminary data up to 2011 are available.
The second data sourcewhere more recent cancer
registration data are availableis the Australian
Mesothelioma Registry. A unique feature of this
data collection is that pathologically confirmed
cases of malignant mesothelioma recorded at the
state or territory level are fast-tracked to this registry,
in order to collect, if possible, information regarding
an individuals asbestos exposure. The Australian
Mesothelioma Registry regularly reports on its data
collection. The most recent report includes data for
the period July 1, 2010, to December 31, 2014, and
current as of May 31, 2015.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 175
Australia is made up of eight states and terri-
tories, most commonly referred to as jurisdictions.
Asbestos consumption is known to have varied in
Australia by jurisdiction. Although malignant
mesothelioma incidence rates are published by
each of the eight subnational cancer registries in
Australia, there may be differences in the way data
are analyzed and presented. Drawing upon high-
quality global cancer incidence data published by
IARC (Curado et al. 2007; Forman et al. 2013;
Parkin et al. 2002), it is possible to describe
Australian malignant mesothelioma incidence
rate differences by jurisdiction where equivalent
data collection, quality control, and analytic pro-
cedures were used.
Survival
Malignant mesothelioma is almost invariably a
fatal disease with a rapid force of cause-specific
mortality in the first year following diagnosis.
Survival estimates may be measured at the popula-
tion level using cancer-mortality data linkage
methods. The Australian Institute of Health and
Welfare regularly performs a probabilistic data
linkage of records held within the Australian
Cancer Database with records held in the
National Death Index. This enables variables such
as cause of death, fact of death, and date of death
to be calculated. If a person is not recorded as
having died, that person is assumed to be alive at
the end of follow-up. The Australian Institute of
Health and Welfare published population-based
estimates of survival following a malignant
mesothelioma diagnosis, expressed as relative sur-
vival (Australian Institute of Health and Welfare
[AIHW] 2012). Relative survival, a method of
comparing of survival in the cancer population
compared to their expected survival using back-
ground mortality data, can be interpreted as sur-
vival experienced by individuals diagnosed with
malignant mesothelioma after their diagnosis and
accounting for all causes of death. Regression
modeling of relative survival is also possible with
results reported recently for Australian trends over
time in malignant mesothelioma survival
(Dickman et al. 2004; Soeberg et al. 2016).
Asbestos exposure
National data collections
Since the mid 1980s, Australia has made significant
investment in collecting asbestos exposure data from
subjects newly diagnosed with malignant mesothe-
lioma. Three different iterations of this system
were implementedthe Australian Mesothelioma
Surveillance Program, the Australia Mesothelioma
Register, and the recently reestablished Australia
Mesothelioma Registry operating for the last 5 years.
Detailed information regarding the first two data col-
lections are published elsewhere (Driscoll et al. 1993;
Leigh 1995;LeighandDriscoll2003;Leighetal.1991a;
1991b; 2002; Rogers et al. 1991). Briefly, the Australian
Mesothelioma Surveillance Program was active
between 1980 and 1985 and collected voluntary noti-
fications of malignant mesothelioma at the subna-
tional level from clinicians, hospitals, occupational
health divisions, and pathologists. Notified cases of
malignant mesothelioma were confirmed with rele-
vant cancer registries in each jurisdiction. During
19801985, 854 cases of malignant mesothelioma
were notified to the Australian Mesothelioma
Surveillance Program, with tissue for histological
examination available for 777 of those cases (Leigh
et al. 1991b). One of the primary reasons the
Australian Mesothelioma Surveillance Program was
disestablished was the high burden of collecting com-
prehensive asbestos exposure data. The Australian
Mesothelioma Register was then established in 1986
and collected information regarding incident malig-
nant mesothelioma cases, as well as a reduced level of
asbestos exposure histories. Sixty percent of cases had
detailed histories from the Western Australian
Mesothelioma Register or the New South Wales
Dust Diseases Board. The remainder of data were
gathered from responses to a short mailed exposure
questionnaire assessing the occupation, industry, or
circumstances of asbestos exposure, with the question-
naire followed up on four occasions if necessary.
Patterns of asbestos exposure were also previously
noted using national and subnational data from the
Australian Mesothelioma Program (national)
(Ferguson et al. 1987;LeighandDriscoll2003), the
Australian Mesothelioma Register (national) (Leigh
and Driscoll 2003), the Western Australian
Mesothelioma Register (Driscoll and Leigh 2008),
176 M. J. SOEBERG ET AL.
and the New South Wales Dust Diseases Board
(Driscoll and Leigh 2008). From these previous data
collections, the most notable consistent trends nation-
ally are the increase in proportion of cases exposed in
building construction workers from 4 to 30%, power
station workers, electrical workers, and boilermaker or
welder workers. There was also a marked rise in indi-
viduals being exposed in multiple settings, as well as in
home renovation (from 5 to 8% in males; from 4 to
36% in females). Conversely, there was a significant
decrease in the proportion of cases exposed in water-
side and transport work, shipbuilding, and railway
work. There was also a marked reduction in the pro-
portion of cases assessed as having no exposure to
asbestos (from 28 to 4%). The occupations having
the highest lifetime risk, that is, of 5% or greater, are
Wittenoom mine or mill workers (16.6%), power sta-
tion workers (11.8%), railway labor workers (6.4%),
and navy/merchant navy workers (5.1%), as illustrated
in Figure 1.Occupationswithelevatedlifetimerisksof
between 3.1 and 0.7% in order of magnitude include
Wittenoom residents, carpenters or joiners, waterside
workers, plasters, boilermakers or welders, bricklayers,
plumbers, painters or decorators, electrical fitters or
electricians, and vehicle mechanics. The dose-
response relationship between asbestos exposure and
mesothelioma has no threshold, and exposures as
short as 1 day were found. Chrysotile-only exposures
were noted in 4% of cases where the main types of
exposure were through occupational exposure in
automotive mechanic work, as well as individuals
exposed to asbestos products known to contain only
chrysotile and persons involved in production of chry-
sotile-only products.
The registry stopped publicly reporting in 2004 and
it was disestablished in 2007, due to, among other
things, underascertainment of malignant mesothe-
lioma incident cases because of changes in privacy
legislation (Macfarlane et al. 2012). A national forum
was held in 2009 to discuss options for Australians
mesothelioma surveillance system, including collec-
tion of asbestos exposure data for people newly diag-
nosed with malignant mesothelioma. In July 2010, the
Australian Mesothelioma Registry was reestablished
0
5
10
15
20
Wittenoom mine or mill
Power station worker
Railway labourer
Navy/merchant navy
Wittenoom town
Carpenter/joiner
Waterside worker
Plasterer
Boilermaker/welder
Bricklayer
Plumber
Painter/Decorator
Electrical fitter/mechanic/electrician
Vehicle mechanic
All Australian men
All Australian women
Lifetime risk (%) exposed 30-50 years previously
Occupational groups and general population reference estimates
Figure 1. Lifetime risk of malignant mesothelioma in occupational groups exposed 3050 years previously as approximated by Leigh
and Driscoll (2003).
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 177
as a consortium arrangement based at the Cancer
Institute NSW with Safe Work Australia and aca-
demic, cancer registration, and other occupational
health and safety groups. The registry was fully in
operation by January 1, 2011. The main aims of the
Australian Mesothelioma Registry include (1) accu-
rately tracking malignant mesothelioma incidence
and survival over time, (2) better understanding the
relationship between asbestos exposure and malignant
mesothelioma, and (3) identifying changes over time
of asbestos exposure patterns in occupational and
nonoccupational settings.
Collecting newly diagnosed malignant
mesothelioma cases
Through the reestablishment of the Australian
Mesothelioma Registry, notification of malignant
mesothelioma to state and territory cancer registries
is mandatory in Australia. However, there is often a
delay of several years in obtaining complete ascer-
tainment of cancer incident cases from state- and
territory-based cancer registries. A special arrange-
ment is in place for the Australian Mesothelioma
Registry to receive fast-trackednotifications of
any new confirmed cases of malignant mesothe-
lioma from a state or territory on a regular basis.
Individuals diagnosed with malignant mesothe-
lioma are also able to self-notify to the registry,
with a self-notification not fully recorded until the
relevant cancer registry confirms the case.
Collecting and assigning asbestos exposure data
in the Australian Mesothelioma Registry
Detailed methods for the manner in which asbestos
exposure data was assigned are published elsewhere
(Australian Mesothelioma Registry 2015). Briefly, fol-
lowing the receipt of a confirmed malignant mesothe-
lioma case, each cancer registry contacts the relevant
clinician in order to obtain consent to contact the
person with malignant mesothelioma. Consent is pro-
vided if the subject was diagnosed with malignant
mesothelioma from July 1, 2010, is living at the time
of the consent being given and is well enough to
participate. Once consent is granted, the person with
malignant mesothelioma is contacted by the cancer
registry to ask for his or her consent to participate in
the collection of asbestos exposure data. Each
consenting individual is provided with a postal ques-
tionnaire relating to his or her asbestos exposure his-
tory. Based upon data collected from the postal
questionnaire, a tailored telephone interview is then
conducted using a Web-based application called
OccIDEAS (Fritschi et al. 2009;Macfarlaneetal.
2012). All participants, regardless of their occupational
history, are asked about asbestos exposure in occupa-
tional and nonoccupational environments, including
their home renovation activity. Exposure assessment
algorithms available in OccIDEAS then determine the
likelihood of asbestos exposure in occupational and
nonoccupational settings.
For the purpose of the Australian Mesothelioma
Registrys public reporting, each person is assigned
as having probable, possible, or unlikely asbestos
exposure above background exposure levels, with
probable exposure further defined into high, med-
ium, and low likelihoods for asbestos exposure. The
assessment of asbestos exposure does not account
for duration, frequency, or intensity of asbestos
exposure. A sequential process is used such that
occupational asbestos exposure is first assessed. If
it is considered that a subjects occupational asbestos
exposure was unlikely, questions regarding that per-
sons nonoccupational asbestos exposure are then
initiated. If an individual completed a number of
job-specific questions in the same field, then the
highest probability of exposure is recorded.
A limitation of the current consent system in the
Australian Mesothelioma Registry is the potential for
time lags in the process of collecting asbestos expo-
sure data from people newly diagnosed with malig-
nant mesothelioma (Champion De Crespigny et al.
2014). The Australian Mesothelioma Registry is
working with cancer registries and clinicians to
reduce these time lags.
Overall patterns in incidence and survival
Number of incident cases
During 19822011, 13,036 individuals were newly
diagnosed with malignant mesothelioma in
Australia. A further 778 cases were identified
between 1945 and 1981 from retrospective searches
and the first 2 years of the Australian Mesothelioma
Program. Data reported by the Australian Institute
for Health and Welfare of 20092011 and the
178 M. J. SOEBERG ET AL.
Australian Mesothelioma Registry for 20122013 are
yet to be finalized (Australian Institute of Health and
Welfare (AIHW) 2015); however, the number of
incident malignant mesothelioma cases appears to
have reached a maximum (Figure 2). In 2011, 692
new cases of malignant mesothelioma occurreda
20% increase in the number of cases recorded in
2001 (n= 576). However, the numbers in 2012 and
2013 were 713 and 676, respectively, suggesting the
maximum was attained, even if some late notifica-
tions for 2013 are allowed for. The number of inci-
dent cases is a useful measure for understanding the
burden on health care and occupational compensa-
tion systems. However, age-standardized incidence
rates are a more useful measure to assess population-
level disease burden, as these incidence rates account
for changes over time in the composition of the
general population.
Incidence rate patterns
Up-to-date data on malignant mesothelioma age-
standardized incidence rates, calculated using differ-
ent age weights, are regularly published by the
Australian Institute of Health and Welfare
(Australian Institute of Health and Welfare [AIHW]
2015). The most recent data available are for the 1982
2011 period. The age-standardization weights include
anationalagedistributionweightandtwointerna-
tional age distribution weights. To assist with inter-
pretation of data, this section presents data using all
three weights with the remaining results presented
using the Australian Standard Population only.
Further, age-standardized mortality rates for malig-
nant mesothelioma are similar in magnitude to inci-
dence rates. This is due to the fact that the majority of
individuals with malignant mesothelioma who died in
aparticularyearwouldhavebeendiagnosedinthe
preceding 1224 mo. For this reason, incidence rates
are the focus here.
Regardless of the weights used, there was a sig-
nificant elevation in the age-standardized inci-
dence rate for malignant mesothelioma in
Australia from 1982 up to the early 2000s
(Figure 3). The highest age-standardized incidence
rate during 19822011 occurred in 2003, with rates
of 3.2, 2.2, and 1.9 per 100,000 using the
Australian, WHO, and Segi World standard
202
290
394
480
613
671
713
0
100
200
300
400
500
600
700
800
1980 1985 1990 1995 2000 2005 2010 2015
Annual number of
incident cases
Calendar year of diagnosis
Males (AIHW) Females (AIHW) Persons (AIHW)
Males (AMR) Females (AMR) Persons (AMR)
Figure 2. Number of people newly diagnosed with malignant mesothelioma, Australia, 19822014, by calendar year of diagnosis.
Data for 19822010 were extracted from aggregate data published by the Australian Institute of Health and Welfare (AIHW) in 2015.
Data for 20112014 were extracted from aggregate data published by the Australian Mesothelioma Registry (AMR) in 2015.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 179
populations, respectively. The corresponding fig-
ures for 2011 are 2.8, 1.9, and 1.6 per 100,000.
There appears to be a plateau in the age-standar-
dized incidence rates during 20032011.
As of May 2015, the age-standardized malignant
mesothelioma incidence rate for 2012 and 2013
reported by the Australian Mesothelioma Registry
was 2.8 and 2.6 per 100,000, respectively. However,
these data need to be interpreted with some cau-
tion as the 2012 and 2013 incidence rates are
marginally underestimated due to the length of
time between a possible case of malignant
mesothelioma being pathologically confirmed in
population-based cancer registration systems.
Differences by age group
There are differences in the trajectory of malignant
mesothelioma over time by age group (Figure 4).
There has been little change over time for the
youngest age group, those of age 1544 years,
with an age-specific incidence rate in 2011 of 0.3
per 100,000. The age-specific incidence rate for
subjects 5564 years of age peaked in 1998, a rate
of 7 per 100,000, with a slow, steady decline with a
rate of 4 per 100,000 in 2011. For individuals of
age 6574 years, incidence leveled off since 1997,
where the age-specific incidence rate remained
between 13 and 14 per 100,000. The steep increase
in the age-specific incidence rates for the oldest
two age groups is such that there has been a con-
vergence in the age-specific incidence rates for
people of age 7584 years and those 85 years and
older. In 2011, the age-specific incidence rate for
subjects of age 7584 years was 22.2 per 100,000
with a similar figure (22.4 per 100,000) for indivi-
duals 85 years or older. Notably, the age-specific
incidence rate for people age 85 years or older
doubled since 1997 (9.9 per 100,000).
Differences by gender
There have also been different trajectories of
malignant mesothelioma incidence rates in
Australia by gender (Figure 5). There was a
marked increase in the male age-standardized inci-
dence from 1982 up to the early 2000s. During
19822011, the highest age-standardized incidence
3.2
2.8
1.9
1.6
2.2
1.9
0
1
2
3
4
5
1980 1985 1990 1995 2000 2005 2010
Age-standardised
incidence rate per 100,000
Calendar year of diagnosis
Australian Standard Po
ulation Se
i World Po
ulation WHO World Po
ulation
Figure 3. Age-standardized incidence rates per 100,000 person-years for people diagnosed with malignant mesothelioma, Australia,
19822011, by calendar year of diagnosis and population standard. Data were extracted from aggregate data published by the
Australian Institute of Health and Welfare in 2015.
180 M. J. SOEBERG ET AL.
0.3
4.0
14.1
22.2
22.4
0
5
10
15
20
25
30
1985 1990 1995 2000 2005 2010
Age-specific incidence rate
per 100,000
Calendar year of diagnosis
15-54
y
ears 55-64
y
ears 65-74
y
ears 75-84
y
ears 85+
y
ears
Figure 4. Age-specific incidence rates per 100,000 for people ages 1599 years who were diagnosed with malignant mesothelioma
in Australia, 19822011, by calendar year of diangosis. Age-specific incidence rates were calculated using aggregate data published
by the Australian Institute of Health and Welfare in 2015.
3.9
5.9
4.9
0.4
0.9
0
1
2
3
4
5
6
7
1980 1985 1990 1995 2000 2005 2010
Age-standardised
incidence rate per 100,000
Calendar year of diagnosis
Males Females
Figure 5. Age-standardized incidence rates per 100,000 for men and women who were diagnosed with malignant mesothelioma in
Australia, 19822011, by calendar year of diagnosis. Age-specific incidence rates were calculated using aggregate data published by
the Australian Institute of Health and Welfare in 2015.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 181
rate for men was in 2003, a rate of 5.9 per 100,000,
with the rate stabilizing around 5 per 100,000 since
that time point. Although the burden of malignant
mesothelioma in Australia primarily affects men, a
slow, steady rise in female age-standardized inci-
dence rate was also observed. In 1990, the rate for
females was 0.43 per 100,000 with a doubling of
the rate in 2010, a rate of 0.98 per 100,000. One
way of describing the different disease trajectories
by gender is to examine absolute and relative dif-
ferences between male and female rates. Between
1990 and 2010, absolute difference between the
two rates remained stable with an absolute differ-
ence between male and female rates of between 3
and 4. A simple calculation of relative differences
comparing male to female incidence rate, a ratio of
the two rates, shows a narrowing of the relative
difference during 19902010. This ratio was 9 in
1990 (the relative difference between 3.9 per
100,000 rate for men and 0.4 per 100,000 rate for
women) and reduced to 5 in 2010 (4.9 per 100,000
for men and 0.98 per 100,000 for women).
Differences in incidence by jurisdiction
During 20032007 (Figure 6), incidence rates were
highest in Western Australia (4.5 per 100,000),
with New South Wales, Queensland and South
Australia displaying rates of approximately 3 per
100,000 and rates of between 2 and 2.9 per 100,000
in the remaining states and territories (Australian
Capital Territory, Northern Territory, Tasmania,
and Victoria).
The highest age-standardized malignant mesothe-
lioma incidence rates occurred in Western Australia
(Figure 6). However, a consistent pattern is emerging
of these rates declining over time. The age-standar-
dized incidence rate for Western Australia during
19931997 was 5.2 per 100,000, compared to 4.7 per
100,000 during 19982002 and 4.5 per 100,000 in
20032007. The finite nature of Western Australias
malignant mesothelioma incidence was also
described by Musk and colleagues (2015). The inci-
dence rates have been stable over time in New South
Wales and Victoria. A recent study published using
individual unit record malignant mesothelioma data
from the NSW Central Cancer Registry during
19722009 also demonstrated stabilization in age-
standardized rates but an increase in the annual
number of malignant pleural mesothelioma cases
(Soeberg et al. 2015). Notably, there was little change
over time in the incidence of malignant peritoneal
mesothelioma over the 38-yr period, with age-stan-
dardized incidence rates ranging between 0.1 and 0.2
per 100,000 person-years. The point estimates for
Tasmania appear to have increased over time but
with wide confidence intervals. Incidence rates for
Queensland and South Australia rose in 19982002
with a small decline in the most recent period (2003
2007). Smaller case numbers in the Australian
Capital Territory and the Northern Territory make
meaningful interpretation of these data more diffi-
cult. Continuous monitoring of these geographic
differences in the age-standardized incidence rates,
particularly the fall in incidence in Western
Australia, might provide important information for
understanding the future trajectory of malignant
mesothelioma in Australia.
Changes over time in survival
There have been small improvements in survival 1
yr following a malignant mesothelioma diagnosis,
particularly in the most recent calendar period
(Figure 7). One-year relative survival in 2006
2010 was 44.3, compared to 36.9% in 19941999.
However, there has been little change over time in
5-yr relative survival (Figure 7). During 1982
1987, 5-yr relative survival was 5.5%, similar to
the estimate for 20062010, 6.2%.
Small improvements in 1-yr relative survival are
most likely explained by earlier and more accurate
diagnosis, including greater ability to detect histo-
logical subtypes, as well as potentially the role of
radical surgical treatment recommended for a
number of patients based upon age, gender,
patient performance, histological subtype, and pre-
sence of other comorbidities (Cao et al. 2011a;
2011b; Linton et al. 2014). Improvements in che-
motherapy may also explain changes over time in
1-yr relative survival shown here. Pemetrexed, in
combination with cisplatin, was found to increase
survival rates (Fennell et al. 2008). However in
Australia, pemetrexed for patients with malignant
pleural mesothelioma was not widely available
until 2008. This investigation presents case data
only up to the end of 2010 and capturing only
182 M. J. SOEBERG ET AL.
0
2
4
6
per 100,000
per 100,000
per 100,000
per 100,000
per 100,000
per 100,000
per 100,000
per 100,000
Calendar period of diagnosis
Australian Capital Territory
0
2
4
6
Calendar period of diagnosis
New South Wales
0
2
4
6
Calendar period of diagnosis
Northern Territory
0
2
4
6
Calendar period of diagnosis
Queensland
0
2
4
6
Calendar period of diagnosis
South Australia
0
2
4
6
Calendar period of diagnosis
Tasmania
0
1
2
3
4
5
6
Calendar period of diagnosis
Victoria
0
2
4
6
1993-1997 1998-2002 2003-2007 1993-1997 1998-2002 2003-2007
1993-1997 1998-2002 2003-2007 1993-1997 1998-2002 2003-2007
1993-1997 1998-2002 2003-2007 1993-1997 1998-2002 2003-2007
1993-1997 1998-2002 2003-2007 1993-1997 1998-2002 2003-2007
Calendar period of diagnosis
Western Australian
Figure 6. Age-standardized incidence rates for men diagnosed with malignant mesothelioma, Australia 19932007, by jurisdiction
and calendar period of diagnosis. Data were extracted from aggregate data published by the International Agency for Research on
Cancer in volumes 810 of the Cancer Incidence in Five Continents reports.
44.3
0
20
40
60
80
100
Relative
survival (%)
Calendar period of diagnosis
1-year relative survival
6.2
0
20
40
60
80
100
1982-1987 1988-1993 1994-1999 2000-2005 2006-2010 1982-1987 1988-1993 1994-1999 2000-2005 2006-2010
Relative
survival (%)
Calendar period of diagnosis
5-year relative survival
Figure 7. One-year and five-year relative survival ratios with 95% confidence intervals for people diagnosed with malignant
mesothelioma, Australia, 19822010, by calendar period of diagnosis. Data were extracted from aggregate data published by the
Australian Institute of Health and Welfare in 2012.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 183
2 yr of data since the time when pemetrexed was
made widely available. More recent data (with
completed mortality follow-up data) would be
required to test whether survival improvements
are noted following introduction of pemetrexed,
as investigated, for instance, in the Netherlands
(Damhuis, Schroten, and Burgers 2012).
Use of aggregate compared to individual unit
record data
These aggregate incidence and survival data provide
an important basis for understanding overall pat-
terns of malignant mesothelioma. However, deiden-
tified individual unit records are a more valuable data
source for quantifying temporal trends and survival
by various patient and tumor factors. Data suggest
that the magnitude in changes over time in incidence
of malignant mesothelioma varies by age group and
tumor location. A descriptive epidemiology study
from the United States by Moolgavkar, Meza, and
Turim (2009) depicted a significant increase over
time in the age-standardized incidence rate for men
diagnosed with malignant pleural mesothelioma
during 19732005, with little alterations over time
in the female incidence rate. Moolgavkar, Meza, and
Turim (2009) reported no marked change in inci-
dence of malignant peritoneal mesothelioma during
the same calendar period of diagnosis. It is worth-
while noting that these data presented by
Moolgavkar, Meza, and Turim (2009) were extracted
from cancer registration data sources that represent
approximately 14% of the total cancer cases recorded
in the United States. In Australia, however, the male
peritoneal mesothelioma rate was elevated approxi-
mately fivefold between 19821988 and 2002, and
female peritoneal mesothelioma rate rose approxi-
mately twofold. Overall the peritoneal mesothelioma
rate increased approximately 4-fold (National
Occupational Health and Safety Commission
(National Institute of Occupational Health and
Safety) 19892004). Diagnostic accuracy is an impor-
tant source of potential bias in ascertaining malig-
nant peritoneal mesothelioma cases from registry
data, as they may be misdiagnosed as malignancies
in other abdominal organs, for example, the ovary
(Nielsen et al. 1994). It is also possible that malignant
peritoneal mesothelioma is diagnosed more com-
monly among subjects with known prior asbestos
exposure (Boffetta 2007). Further, the best available
evidence to date suggests that exposure to asbestos
has a causal association with malignant peritoneal
mesothelioma but that this relationship is weaker
than for malignant pleural mesothelioma (Cocco
and Dosemeci 1999;Coggonetal.1995; Hodgson
and Darnton 2000). Other etiological factors also
cannot be excluded for their association with malig-
nant peritoneal mesothelioma, including exposure to
erionite (Baris et al. 1981; 1987), ionizing radiation
(Andersson et al. 1995), simian virus 40 (Shivapurkar
et al. 2000), and chronic pancreatitis (Peterson,
Greenberg, and Buffler 1984). The strength of the
evidence for these other factors is more limited.
Further, symptoms of malignant peritoneal mesothe-
lioma are generally nonspecific and might include
increased abdominal girth, pain, and weight loss
(Sugarbaker et al. 2002; Turner, Varghese, and
Alexander 2012).
Recently individual-level data were obtained from
the Australian Institute of Health and Welfare and
the Australian Mesothelioma Registry for people
diagnosed with malignant mesothelioma in
Australia during 19822012. Data were analyzed on
10,930 individuals with malignant pleural mesothe-
lioma and 640 subjects with malignant peritoneal
mesothelioma diagnosed in Australia during 1982
2009 (Soeberg et al. 2016). Trends over time were
measured in age-standardized incidence rates, and a
rapid decline was found in these rates among men
diagnosed with malignant pleural mesothelioma of
ages 064 years during 20032009, an average
annual change of 5.1%. This was in contrast to the
increase over time in the age-standardized incidence
rate among men aged 75 years or more with malig-
nant pleural mesothelioma. Age-specific incidence
rates were also projected for malignant mesothe-
lioma in Australia up to 2030 using age-period-
cohort modeling. Overall, it was concluded that
Australias malignant mesothelioma incidence rates
appears to have reached maximal levels but with
differences over time by age, gender, and tumor
location. In particular, a rise up to 2020 is projected
for malignant pleural mesothelioma in men of age
75 years or older. In addition, there may be an
increase in age-specific incidence rates up to 2025
among men of age 65 years or older diagnosed with
malignant peritoneal mesothelioma. Large survival
differences were also observed by histological
184 M. J. SOEBERG ET AL.
subtype among individuals diagnosed with malig-
nant mesothelioma. Continuous tracking of these
population-level malignant mesothelioma data may
contribute to the understanding of the curve of the
asbestos-related disease epidemic in Australia, as
well as assisting in the evaluation of the implementa-
tion of recently published Australian guidelines for
diagnosis and treatment of malignant pleural
mesothelioma (van Zandwijk et al. 2013).
Overall patterns in asbestos exposure
Between July 1, 2010, and April 1, 2015, in total,
449 people were recorded on the current Australian
Mesothelioma Registry as having completed both
postal questionnaires and telephone interviews
(Table 1). The majority of subjects were assessed
as having probable or possible occupational asbes-
tos exposure (n= 268, 60%). Of the occupational
asbestos categories, 88 individuals were assessed as
having a high probability that their asbestos expo-
sure occurred in construction jobs, for example, as
a carpenter, joiner, builder, or bricklayer. The next
largest job category where asbestos exposure was
highly probable was metal and mechanical trades
(n= 48), including jobs such as fitters, turners, and
machinists. This was followed by other job types
(not specified, n= 27) and electricians (n= 25). It is
noteworthy that all boilermaker and welding cases
(n=21)wereconsideredtohavehadprobable
asbestos exposure, with all cases categorized as
high likelihood. A similar pattern occurred for
plumbers, with all but one case being categorized
as having highly probable asbestos exposure in this
job (n= 18). Sparse data for engineers and tele-
communication technicians make meaningful inter-
pretation more difficult.
All of the 449 participants in the Australian
Mesothelioma Registry received an asbestos expo-
sure module to assess their nonoccupational asbestos
exposure, including those individuals who were
assessed for occupational asbestos exposure. From
these data, 377 participants were reported as having
possible or probable asbestos exposure in nonoccu-
pational settings, with the remaining 72 cases
assessed as not having possible or probable asbestos
exposure above background levels. Fifty-five subjects
reported ever living in a house made mainly of
asbestos cement sheeting (referred to in Australia
as fibro) that was built between 1947 and 1987.
Further information regarding occupational and
nonoccupational asbestos exposure categories may
be found at https://www.mesothelioma-australia.
com. While these data are informative, an important
consideration when interpreting these data is the
extent to which they are considered representative
of the entire malignant mesothelioma case series as
recorded by the current Australian Mesothelioma
Registry (n= 2,722). A comprehensive interpretation
of the Australian Mesothelioma Registry asbestos
exposure data needs to include consideration of
asbestos exposure data collected through the
Australia Mesothelioma Register and the Australian
Mesothelioma Surveillance Program, as well as state-
based data collections including the Western
Australian Mesothelioma Registry and malignant
mesothelioma data from the NSW Dust Diseases
Board (recently renamed to the Dust Diseases
Authority).
Subnational data collections
In addition to national data collections, there are
also state-based data collections that contain
important information regarding asbestos expo-
sure and its role as an etiological factor and as a
prognostic factor (de Klerk et al. 2013; Kao et al.
2013a;2013b; Olsen et al. 2011; Park et al. 2013;
Robinson et al. 2014; van Oyen et al. 2015). These
data collections are primarily held in Western
Australia and New South Walesstates with
known high levels of asbestos mining and produc-
tion of asbestos-containing products. An impor-
tant advantage of use of these state-based data sets
is that clinical data are also often collected, making
data more amendable to comprehensively investi-
gating various prognostic factors additional to data
fields more traditionally collected in population-
based cancer registries. Linton et al. (2014) utilized
comprehensive data on participants who devel-
oped malignant pleural mesothelioma as a result
of asbestos exposure during their employment in
New South Wales collected by the Workers
Compensation Dust Diseases Board (DDB). The
investigators were able to incorporate asbestos
exposure data, namely, age at first asbestos expo-
sure, into univariate and multivariate analyses to
investigate prognostic factors for longer term
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 185
malignant pleural mesothelioma survival. These
compensation-based data also contained addi-
tional data regarding asbestos exposure that may
be used in the future in conjunction with recently
published jobexposure matrices developed in
Australia (van Oyen et al. 2015). This jobexpo-
sure matrix identified that the highest exposures
occurred in shipyard, wharf, navy, marine, carpen-
try, joinery, boiler making or welding, power, rail-
way, and insulation workers, and were classified
corresponding to the highest lifetime risks calcu-
lated from mesothelioma register data (Leigh and
Driscoll 2003).
Conclusions
In this paper, descriptive epidemiological data were
presented from two high-quality national cancer regis-
tration data sourcesthe Australian Cancer Database
and the Australian Mesothelioma Registry. From
these data, it can be determined that the annual num-
ber of malignant mesothelioma cases and the age-
standardized malignant mesothelioma incidence rate
reached a maximum, as predicted in 1997 by Leigh,
Hull, and Davidson (1997). In addition, subnational
variations were found in the incidence of malignant
mesothelioma with declines in Western Australias
age-standardized incident rate occurring over time
but little change for other states, including New
South Wales, Queensland, and Victoria. Marked
increases were noted over time in age-specific inci-
dence rates for people aged 75 years or greater and a
decline in the age-specific incidence rate in the last
1015 years for younger age groups. Using popula-
tion-based survival analyses, little change was found
over time in survival 5 years following a malignant
mesothelioma diagnosis. While these data provide
important information, more granular investigation
of patterns is warranted. For instance, it is likely that
there are different disease trajectories by tumor loca-
tion, namely, pleural and peritoneal mesothelioma,
and that survival outcomes are likely to differ by age
group, gender, and histological subtype.
Using data from the Australian Mesothelioma
Registry, it was demonstrated that the majority
(60%) of individuals who had asbestos exposure
data recorded between July 1, 2010, and April 1,
2015, were exposed in occupational settings. Of the
449 cases where asbestos exposure was recorded, 377
people were classified as having probable or possible
nonoccupational asbestos exposure. However, this
figure is inclusive of those participants who were
also classified as having occupational asbestos expo-
sure (n= 268). Collecting accurate and timely infor-
mation with respect to prior asbestos exposure for
people newly diagnosed with malignant mesothe-
lioma is an essential task of the Australian
Mesothelioma Registry and may help answer impor-
tant public health research questions regarding the
subpopulation groups most affected by asbestos-
related disease and the targeting of current and
future prevention interventions. An important chal-
lenge for the Australian Mesothelioma Registry, and
its consortium partners, is how to elevate the pro-
portion of newly diagnosed malignant mesothelioma
cases whose asbestos exposure histories are
documented.
The epidemic of malignant mesothelioma con-
tinues to remain an important public health and
clinical challenge in Australia. Simultaneous con-
sideration of descriptive epidemiological data,
including patterns by tumor location, age, gender,
and histological subtype, as well as occupational
and nonoccupational asbestos exposure data, has
the potential to provide meaningful interpretation
of the trends in asbestos-related diseases in
Australia.
Conflict of interest
None.
Notes on contributor
M.S. was the primary author of the article, with J.L. and N.v.
Z. contributing content on epidemiological exposure data
and clinical and treatment aspects, respectively. All authors
revised the article for intellectual content.
Funding
This research was funded by a Translation Program Grant
awarded to the Asbestos Diseases Research Institute by the
Cancer Institute NSW (11/TPG/3-06).
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JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART B 189
... 1 Most cases of MPM are associated with a history of asbestos exposure, with an incubation period of 10 to 50 years or more. 2 And chrysotile, crocidolite or amosite asbestos are the three main types of asbestos that cause MPM. Occupational asbestos exposure is the most common, such as building construction workers, power station workers, electrical workers and boilermaker. ...
... Occupational asbestos exposure is the most common, such as building construction workers, power station workers, electrical workers and boilermaker. 2 There are three main histological subtypes of MPM: biphasic, epithelioid and sarcomatoid. Among them, the sarcomatoid variant has the worst prognosis, with a median survival time of only 4 months. ...
Article
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that originates from pleural mesothelial cells. In recent years, with the development of asbestos-related industries and the increase in air pollution, its incidence has been increased. The incidence of pulmonary embolism combined with sarcomatoid MPM is very low and the prognosis is extremely poor. We here report a case of a patient with long term of pleural effusion and finally diagnosed as pulmonary embolism with sarcomatoid MPM. Case: A 75-year-old male with a 30-year history of asbestos exposure was admitted to our hospital due to chest pain and difficulty in breathing after exercise. Radiologic examination revealed pleural effusion, computed tomography pulmonary angiography (CTPA) suggests pulmonary embolism, and we consider pleural effusion caused by pulmonary embolism. After anticoagulant therapy for pulmonary embolism and pleural puncture to reduce pleural effusion, the patient's symptoms improved. However, after that, the patient was still admitted to the hospital several times because of recurrent chest pain and dyspnea symptoms, and radiologic examination always showed unexplained pleural effusion. Finally, pathological and immunohistochemical examinations of the pleural biopsy specimens were performed, and the diagnosis was confirmed as sarcomatoid MPM. Conclusion: In summary, sarcomatoid MPM with pulmonary embolism is relatively rare, and the prognosis is poor. Clinicians need to be alert to its occurrence. When the first diagnosis is confirmed and the effect of targeted treatment is still not good, the possibility of other diseases should be considered. In clinical practice, pleural biopsy guided by PET-CT is a good choice for patients with sarcomatoid MPM who cannot tolerate open pleural biopsies or thoracoscopy. And patients should undergo pleural morphology and immunohistochemistry as soon as possible, which are helpful for timely diagnosis.
... Malignant mesothelioma (MMe) is an uncommon and aggressive cancer (1) mostly associated with asbestos exposure (2,3). Other causes of mesothelioma include exposure to other types of mineral fibers, radiation, chronic pleural inflammation, or germline and somatic inactivation of the BRCA1-associated protein 1 gene (BAP1) (4,5). ...
Article
Full-text available
Background: Malignant mesothelioma (MMe) is a rare and fatal cancer with a poor prognosis. Our study aimed to compare the overall survival (OS) of MMe patients across various sites and develop a prognostic model to provide a foundation for individualized management of MMe patients. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 1,772 individuals with malignant mesothelioma (MMe) were identified. The X-tile software was used to identify the optimal cut-off point for continuous variables. The Kaplan-Meier method was employed to compare the survival of MMe across different sites. The Cox proportional hazards model was applied to identify the independent risk factors of overall survival (OS) and a nomogram was constructed. Results: In the survival analysis, MMe originating from the reproductive organs and hollow organs showed a relatively better prognosis than those originating from soft tissue, solid organs, and pleura. Age, gender, location, histological type, grade of differentiation, extent of disease, lymph node status, lymph node ratio (LNR), and chemotherapy were all found to be independent risk variables for the prognosis of MMe patients (P<0.05) in a multivariate Cox analysis and were included in the construction of nomogram. In the training and testing sets, the C-index of the nomogram was 0.701 and 0.665, respectively, and the area under the ROC curve (AUROC) of the 1-, 3-, and 5-year overall survival rate was 0.749, 0.797, 0.833 and 0.730, 0.800, 0.832, respectively. The calibration curve shows that the nomogram is well-calibrated. Conclusions: This is the first research to examine the prognosis of MMe patients based on the location. However, previous studies often focused on malignant pleural mesothelioma or malignant peritoneal mesothelioma with high incidence. Furthermore, a nomograph with good prediction efficiency was established according to the variables that influence patient survival outcomes, which provides us with a reference for clinical decision-making.
... According to the WHO and foreign literature sources, the majority of mesothelioma cases (according to some sources up to 90%) are the result of asbestos exposure (16). In the Australian Mesothelioma Registry, an occupational origin was detected in 60% of cases (17). ...
Article
Full-text available
Objectives: In the Czech Republic, asbestos has been classified as a known human carcinogen since 1984. The use of asbestos-containing products was limited to scenarios where the use of other materials was not possible. Since 1997, the manufacture of asbestos materials has been forbidden, and in 1999, the import, manufacture and distribution of all types of asbestos fibres was legally banned by Act No. 157/1998 Coll. Although the use of asbestos is forbidden, the risk of exposure still exists given the ongoing demolition and reconstruction of buildings in which asbestos has been used. In addition, a novel risk has arisen through the quarrying of asbestos-containing aggregates and their subsequent use. The aim of this paper was to describe and evaluate asbestos in terms of history, legislation, current risk of occupational exposure and its health consequences in the Czech Republic over the last three decades. Methods: This retrospective descriptive study used the collected data on occupational exposure and occupational diseases. The counts of workers occupationally exposed to asbestos were obtained from the Registry of Work Categorization; the numbers and structure of occupational diseases caused by asbestos were taken from the Czech National Registry of Occupational Diseases. Data on the total number of mesothelioma cases recorded in the Czech National Cancer Registry was provided by the Institute of Health Information and Statistics of the Czech Republic. Results: A total of 13,112 subjects were registered as occupationally exposed to asbestos during the period 2001-2020. A total of 687 cases of asbestos-related occupational diseases were reported in the period 1991-2020 in the Czech Republic, comprising 178 cases of asbestosis, 250 cases of pleural hyalinosis, 168 cases of pleural or peritoneal mesothelioma, 90 cases of lung cancer, and one case of laryngeal cancer. The data from the Czech National Cancer Registry, available for a shorter period (1991-2018), reveal 1,389 cases of mesothelioma, of which only ~11% were recognised as occupational, despite the fact that the occupational causality of mesotheliomas is estimated to be up to 90% of mesotheliomas. Moreover, the latency of mesotheliomas since the last occupational exposure reached up to 50 years and this trend is still slightly increasing, unlike asbestosis, where a high cumulative dose of inhaled asbestos is needed. The real proportion of occupational lung cancers may obviously be even higher, especially in smokers, where occupational causes including asbestos are not suspected by most physicians. Conclusion: Czech data on asbestos-related occupational diseases, especially cancers, are grossly underestimated, which is most apparent through the low proportion of mesotheliomas diagnosed as occupational. Asbestos materials in older buildings remained in situ and may represent a danger during reconstruction works. The current source of exposure appears to be quarrying of asbestos-containing aggregate and its subsequent use. Awareness of the professional community is therefore crucial, not only for the possibility of compensating those affected, but also for the early detection of the diseases through the dispensary of exposed persons.
... Consistent with previous reports [33], SIRs were highest in many areas of Western Australia, which has a history of mining and use of crocidolite, the most carcinogenic form of asbestos. Lower rates but high counts were observed around the chrysotile mines in northern New South Wales that were active mines more recently [9]. ...
Article
Objectives To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia. Materials and Methods Generalised linear models and Bayesian spatial models were fitted using population registry data. Area-level covariates were socioeconomic quintile, remoteness category and state or territory. The maximised excess events test was used to test for spatial heterogeneity. Results There was strong evidence of spatial differences in standardised incidence rates for malignant mesothelioma but survival was uniformly poor. Incidence rates varied by state or territory and were lower in remote areas. Patterns in the geographic distribution of modelled incidence counts for malignant mesothelioma differed substantially from patterns of standardised incidence rates. Conclusions Geographic variation in the modelled incidence counts of malignant mesothelioma demonstrates varying demand for diagnostic and management services. The long latency period for this cancer coupled with migration complicates any associations with patterns of exposure, however some of the geographic distribution of diagnoses can be explained by the location of historical mines and asbestos-related industries.
... This is particularly important given the prolonged disease burden due to chrysotile, which arises for two reasons. First, asbestosrelated cancers typically arise several decades after the first exposure, as demonstrated in countries that now have the highest mesothelioma mortality rates worldwide, all of which have long banned the use of asbestos (e.g., Australia, Germany) [9][10][11]. Second, even in the absence of active mining and use of chrysotile, exposure to chrysotile would be expected to continue worldwide due to its persistence in the environment (e.g., the presence of chrysotile in the Earth's crust) and ongoing exposures such as those arising from repair or removal work (e.g., related to maintenance or demolition of materials containing chrysotile). ...
Conference Paper
Introduction A historical cohort study in workers occupationally exposed to chrysotile was set up in the town of Asbest, the Russian Federation, to study their cause-specific mortality, with a focus on cancer. Objective Describe the Asbest Chrysotile Cohort established in 2013. Methods Cohort enrolment was based on employment records from JSC Uralasbest chrysotile mine and processing factories. Exposure assessment was based on detailed occupational histories extracted from company archives and personal workbooks linked to > 90,000 measurements, and conversion factors derived using a subset of parallel dust/fibre measurements. This resulted in yearly dust and fibre estimates for each employed calendar year. Vital status was ascertained from multiple sources including company records, the Pension Fund, the Federal Migration Service, and Civil Act Registration Office providing the date and cause of death of those deceased in Sverdlovsk Region. Results The cohort comprises 22,463 men and 13,374 women working ≥1 year between 01/01/1975 and 31/12/2010 in JSC Uralasbest and followed until 31/12/2015. Cumulative exposure of exposed women was higher than for men (49 mg/m3 dust years and 33 fibres/cm3 years vs. 31 mg/m3dust years and 19 fibres/cm3years). At the end of follow-up, 52% of the cohort was alive, 36% deceased, and 12% censored at last date known to be alive in the Sverdlovsk Region. For those who died the mean age at death was 59.4 years for men and 66.5 for women. The most frequent underlying cause of death for all was circulatory diseases, followed by external causes and cancer in men, and cancer and external causes in women. Cancer mortality was dominated by lung cancer in men and breast cancer in women. Conclusion The cohort is unique in its size, long follow-up, and substantial proportion of female workers. The cohort is relatively young, and the mortality patterns follow those of the Russian population. Risk analyses are underway.
... As the risk of MPM increases decades after asbestos exposure, many countries that banned asbestos at the end of the 20th century are just now approaching the peak of cases [12][13][14]. There is substantial uncertainty on how long the MPM epidemic will last both worldwide and in the countries that have banned asbestos use [15]. ...
Article
Full-text available
Statistical models used to forecast malignant pleural mesothelioma (MPM) trends often do not take into account historical asbestos consumption, possibly resulting in less accurate predictions of the future MPM death toll. We used the distributed lag non-linear model (DLNM) approach to predict future MPM cases in Italy until 2040, based on past asbestos consumption figures. Analyses were conducted using data on male MPM deaths (1970–2014) and annual asbestos consumption using data on domestic production, importation, and exportation. According to our model, the peak of MPM deaths is expected to occur in 2021 (1122 expected cases), with a subsequent decrease in mortality (344 MPM deaths in 2039). The exposure–response curve shows that relative risk (RR) of MPM increased almost linearly for lower levels of exposure but flattened at higher levels. The lag-specific RR grew until 30 years since exposure and decreased thereafter, suggesting that the most relevant contributions to the risk come from exposures which occurred 20–40 years before death. Our results show that the Italian MPM epidemic is approaching its peak and underline that the association between temporal trends of MPM and time since exposure to asbestos is not monotonic, suggesting a lesser role of remote exposures in the development of MPM than previously assumed.
... Many studies have estimated the mesothelioma disease burden from mortality data because about half of those diagnosed with mesothelioma die within a year [3]. The disease burden of mesothelioma has been the subject of scientific analyses at global [4,5], regional [6,7], and country levels [8,9]. Recently, many studies using the estimated global and country-level mesothelioma burdens have referenced the Global Burden of Disease (GBD) studies [10][11][12] (C-OO, TD, JT, and KT are GBD contributors), which is widely accepted as a reliable source of data for global health. ...
Article
Full-text available
Background: This study compares estimates of the global-level mesothelioma burden with a focus on how existing national mortality data were utilized and further assesses the interrelationship of country-level mesothelioma burden and asbestos use with national income status. Methods: Country-level mesothelioma deaths in the WHO Mortality Database as of December 2019 were analyzed by national income category of countries in terms of data availability and reliability. Numbers of mesothelioma deaths from the study of Odgerel et al. were reanalyzed to assess country-level mesothelioma death burdens by national income status. Results: Among 80 high-income countries, 54 (68%) reported mesothelioma to the WHO and 26 (32%) did not, and among 60 upper middle-income countries, the respective numbers (proportions) were 39 (65%) countries and 21 (35%) countries, respectively. In contrast, among 78 low-and lower middle-income countries, only 11 (14%) reported mesothelioma deaths while 67 (86%) did not. Of the mesothelioma deaths, 29,854 (78%) were attributed to high-and upper middle-income countries, and 8534 (22%) were attributed to low-and lower middle-income countries. Conclusions: The global mesothelioma burden, based on reported numbers, is currently shouldered predominantly by high-income countries; however, mesothelioma burdens will likely manifest soon in upper middle-income and eventually in low and lower middle-income countries.
Article
A retrospective cohort study was carried out to investigate the mortality of workers occupationally exposed to dust containing chrysotile asbestos fibers. In its chemical and physical properties, it differs from the fibers of other types of asbestos and is the only type of asbestos that is currently approved for use in many countries of the world. The members of the cohort are current and former employees who have worked for at least one year at the production sites of the complex of enterprises for the mining and enrichment of chrysotile asbestos (JSC "Uralasbest", Asbest, Sverdlovsk region) in the period from 01.01.1975 to 31.12.2010. Of the 35,837 members of the cohort, 12,729 (35.5%) people died (2,373 of them were malignant neoplasms of various localizations, including 10 mesotheliomas), 18,799 (52.5%) were alive at the end of the observation period (2015), and 4,309 people (12.0%) were censored by the end of 2015. The mean follow-up period was 21.7 years for men and 25.9 years for women. The average age at death was 59.4 years for men and 66.5 years for women. It is currently the world's largest cohort of workers in the field.
Article
Aims MTAP immunohistochemistry is a specific marker of CDKN2A deletion in malignant mesothelioma. However, the relationship of MTAP expression with MTAP copy number remains unexplored. Methods and Results Forty malignant pleural mesotheliomas were characterized by targeted next‐generation sequencing (29), single nucleotide polymorphism microarray (7), or both (4). Copy number status of MTAP and CDKN2A were correlated with MTAP immunohistochemistry. Twenty‐seven (68%) tumours showed CDKN2A deletion (14 heterozygous, 13 homozygous), of which 20 (74%) showed MTAP co‐deletion (15 heterozygous; 5 homozygous). No tumours showed MTAP deletion without CDKN2A co‐deletion. Immunohistochemical loss of MTAP was seen in 16 (40%) tumours, and was 75% sensitive and 95% specific for MTAP deletion, and 59% sensitive and 100% specific for CDKN2A deletion. Nine of 40 (23%) tumours showed heterogeneous MTAP staining, and the percentage of tumour cells with MTAP loss correlated with molecular detection of MTAP deletion. Conclusions MTAP is frequently co‐deleted with CDKN2A in pleural mesothelioma. However, homozygous deletion of both genes occurs in a minority of tumours (5/40; 13%); CDKN2A deletion often co‐occurs with heterozygous MTAP deletion or neutral MTAP copy number; and MTAP immunohistochemistry correlates inconsistently with heterozygous MTAP deletion. Correspondingly, MTAP immunohistochemistry is a highly specific but only moderately sensitive assay for CDKN2A deletion.
Article
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Malignant pleural mesothelioma (MPM) is an insidious primary neoplasm of the pleura that can be challenging to diagnose and is commonly considered to be only locally invasive. We present the case of a 74-year-old male who presented with clinical features of MPM but from whom pleural fluid and biopsies initially suggested benign pathology. He later developed diffuse bony metastases and re-examination of pleural biopsies using modern immunohistochemistry and molecular testing revealed a diagnosis of sarcomatoid and desmoplastic MPM with heterologous osteosarcomatous differentiation. This case not only demonstrates the rare potential of skeletal metastasis of MPM, but also highlights the importance of recognizing the utility of modern diagnostic tests and their potential to prevent the need for unnecessary invasive procedures. To our knowledge this is the first description of this rare histological sub-type presenting with skeletal metastases.
Article
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Background Australia is known to have had one of the highest per-capita asbestos consumption rates, yet there are few contemporary reports on malignant mesothelioma trends. Methods Data on 10 930 people with malignant pleural mesothelioma (MPM) and 640 people with malignant peritoneal mesothelioma diagnosed in Australia during 1982–2009 were analysed. Observed incidence rate trends were quantified. Incidence rates were projected up to 2030 using observed incident cases during 1982–2012. The relative per-decade change in excess mortality during 1999–2009 was estimated. Results During 1982–2009, acceleration in MPM age-standardised incidence rates were highest for women and those aged 75 years and above, with average annual percentage changes of +4.9 (95% CI 3.6 to 6.2) and +7.2 (95% CI 5.4 to 9.0), respectively. Age-standardised incidence rates for men with MPM aged 0–64 years decelerated rapidly during 2003–2009, an average annual percentage change of −5.1% (95% CI −7.6% to −2.5%). Overall, male age-specific MPM incidence rates in the age group of 65–74 year during 2010–2030 are projected to decline with rates projected to increase for older men and women with MPM. There was a statistically significant 16% relative reduction in the excess mortality rate (EMR) up to 5 years postdiagnosis for people diagnosed with malignant pleural and peritoneal mesothelioma combined in 2009 compared with those diagnosed in 1999, an EMR ratio of 0.84 (95% CI 0.77 to 0.92). Conclusions Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease.
Article
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Background: Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series. Methods: All patients registered with the NSW Dust Diseases Board (2002–2009) were included in an analysis of prognostic factors using Kaplan–Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)). Results: We identified 910 patients: 90% male; histology (epithelioid 60% biphasic 13% sarcomatoid 17%); stage (Tx-I-II 48% III-IV 52%); and calretinin expression (91%). Treatment: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil–lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC). Conclusions: We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.
Article
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Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.
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this article is freely available via PMC http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886874/
Article
Introduction: Malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPeM) are often grouped together in descriptive epidemiological analyses, resulting in limited understanding of epidemiological patterns for these tumour types. Methods: We studied patterns in the incidence, mortality and survival of people diagnosed with MPM (n=4,076) and MPeM (n=293) in New South Wales (NSW), Australia, 1972-2009. We also calculated 5-year relative survival for people diagnosed 1972-2006 followed up to 2007. We assessed patterns for each tumour type and histological subtype and, where possible, by combination of these categories. Results: Annual MPM cases steadily increased over time (n=208 in 2009). There was an increasing trend in the MPM age-standardised incidence rate from 1972 up to 1994. This rate increase has levelled off in the past 10 years. Since 1999, 11 cases of MPeM were diagnosed each year, on average. Five-year relative survival remained stable for MPM and MPeM. However, 5-year relative survival in 2002-2006 was substantially higher for people with MPM epithelioid histological subtype (11.7% [95%CI 6.8-18.2%]) compared to all other non-epithelioid histological subtypes (6.9% [95%CI 5.0-9.1%]), a 70% difference. Survival was also greater for women with MPM (13.4% [95%CI 8.5-19.4%]) compared to men (7.0% [95%CI 5.1-9.2%]). Interpretation: MPM incidence rates have stabilised since the mid-1990s, suggesting that maximum incidence levels have been reached. When more up-to-date data are available, survival estimates should be reanalysed to include people likely to benefit from the wide introduction of combination chemotherapy in 2007, including pemetrexed.
Article
Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions. To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data. A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation. Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; ≥2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml(-1). Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite. The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asbestos-related diseases and attribution of disease causation. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.