Mesothelioma.BMJ

Mesothelioma
Straight to the point of care
Last updated: Nov 04, 2021

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 4
Classification 5
Case history 5
Diagnosis 6
Approach 6
History and exam 9
Risk factors 10
Investigations 12
Differentials 16
Criteria 17
Management 18
Approach 18
Treatment algorithm overview 20
Treatment algorithm 21
Emerging 27
Primary prevention 27
Secondary prevention 28
Patient discussions 28
Follow up 29
Monitoring 29
Complications 30
Prognosis 31
Guidelines 32
Diagnostic guidelines 32
Treatment guidelines 32
References 34
Images 43
Disclaimer 46
Mesothelioma Overview
Summary
Malignant pleural mesothelioma accounts for most malignant mesotheliomas; it is a rare malignancy with an
annual incidence in the US of 3200.
OVERVIEW
Largely caused by exposure to asbestos, with a 20- to 40-year latency period between exposure and
development of malignancy; consequently the typical patient is in the sixth to ninth decade of life.
Most patients present with shortness of breath and chest pain, which on investigation is often found to be
associated with unilateral pleural effusion and pleural thickening.
Despite advances in treatment, malignant pleural mesothelioma remains a highly lethal malignancy with few
long-term survivors.
Definition
Malignant mesothelioma is an aggressive epithelial neoplasm arising from the lining of the lung, abdomen,
pericardium, or tunica vaginalis.[1] It is one of the few cancers related directly to an environmental exposure;
asbestos is the chief causative agent.
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3
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Mesothelioma Theory
Epidemiology
The disease is more common in men and white people, and typically occurs in older adults (sixth to ninth
decade of life).[2] [3] In the UK, the incidence has been increasing rapidly since the 1960s, when the
THEORY
mesothelioma register was established to record cases. Currently it is projected that the annual number of
deaths in the UK will peak some time between the years 2011 and 2015, with 1950 to 2450 deaths.[4] In the
US, the incidence of mesothelioma increased between 1970 and 2000, but seems now to have plateaued.[5]
In the US, there are about 3200 new cases of malignant pleural mesothelioma every year (1.05 per 100,000
people).[6] The annual mortality in the US due to malignant pleural mesothelioma increased from 2479 in
1999 to 2597 in 2015.[7] Global mortality varies widely, ranging from 0.5 deaths per million in Brazil and
Ecuador to 31 deaths per million in the UK. This variation probably reflects country-to-country disparities in
asbestos use and regulation.[8]
Aetiology
Exposure to asbestos is the principal risk factor; about 80% of patients have a history of asbestos
exposure.[9] [10] [11] As of 2013 approximately 125 million people have been exposed to asbestos at
work.[12] Moreover, 50,000 people had malignant mesothelioma and 34,000 died from the disease.[13]
Certain subtypes of asbestos, iron-containing crocidolite and amosite in particular, are thought to be more
carcinogenic than others. There also seems to be a dose-response relationship. The latency period between
exposure and development of malignancy is 20 to 40 years.[5]
Other possible aetiologies include prior exposure to radiotherapy (a known carcinogen); genetic
predisposition e.g., mutation of the BAP1 gene;[14] and the simian virus 40 (SV-40).[15] [16] [17]
Germline mutations in the gene encoding BRCA1 associated protein-1 (BAP1) can predispose carriers to
mesothelioma. Other cancers, in particular uveal and cutaneous melanomas, basal cell carcinomas, and
renal cell carcinomas, have been described in these individuals.[18] [19] Numerous other factors have been
proposed as possible risks for developing malignant pleural mesothelioma; however, further epidemiological
studies are needed to determine their significance.[20]
Pathophysiology
Asbestos exposure is considered the primary causal factor. Studies suggest that exposure to asbestos fibres
results in recruitment and activation of alveolar macrophages and neutrophils, with subsequent generation,
possibly iron-catalysed,[21] of reactive oxygen and nitrogen species.[10] [22] Chronic inflammation and
oxidative stress may culminate in DNA damage, alterations in gene expression (proto-oncogenes and
tumour suppressor genes), and eventual malignant transformation. However, exactly how these asbestos-
induced changes foster the development of malignant pleural mesothelioma remains a topic of considerable
investigation and uncertainty.
Genetic analyses have identified several genetic and genomic alterations in malignant mesothelioma. The
most frequent somatic mutations are neurofibromatosis type 2 (NF2), BRCA1- associated protein-1 (BAP1),
and Cullin 1 (CUL1) genes.[23] The genomic alterations in human malignant mesothelioma that have been
previously reported include losses of chromosome arms 1p, 3p, 4q, 6q, 9p, 13q, 14q, 22q and gains of
chromosome arms 1q, 5p, 7p, 8q, 17q. In addition, dysregulation in signal transduction pathways, related to
cell survival and proliferation, has also been demonstrated.
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 04, 2021.
Mesothelioma Theory
Classification
Anatomical variants
THEORY
• Pleural (about 90% of mesothelioma cases)
• Peritoneal (5% to 10%)
• Pericardial (<1%)
• Testicular (<1%)
Common histological subtypes

• Epithelioid
• Biphasic
• Sarcomatoid
Case history
Case history #1
A 72-year-old man presents to his primary care physician with a history of increasing shortness of breath
over a period of several months. Before his retirement he was a construction worker. Physical examination
reveals decreased breath sounds in the right lung base associated with dullness to percussion.
Other presentations
Although the most common presentation of malignant pleural mesothelioma is shortness of breath
associated with a pleural effusion, patients can also present with a cough, chest pain, and progressive
fatigue. Some patients may be asymptomatic with an incidental finding of a pleural effusion noted
on physical examination or chest x-ray. Abdominal pain and/or distension, with partial small bowel
obstruction, is a common presentation of peritoneal mesothelioma.
5
Mesothelioma Diagnosis
Approach
Malignant pleural mesothelioma is a rare malignancy and can be overlooked as a possible cause of
dyspnoea or a pleural effusion. History of asbestos exposure associated with a pleural effusion is strongly
suggestive; however, the absence of asbestos exposure on history does not exclude this diagnosis. Patients
may be asymptomatic and present with an incidental finding of pleural abnormalities on diagnostic imaging
studies.
Clinical presentation
A careful social history, enquiring about possible asbestos exposure, including source and dates of
exposure, is crucial. Occupational history regarding the type of work performed (shipyard; construction;
maintenance; vehicle brake mechanic; asbestos cement; insulation; or production of tiles, shingles,
gaskets, brakes, or textiles) may provide some clues. Men are predominantly affected (male to female
ratio 3:1) and as the latency period between exposure to asbestos and development of malignant pleural
mesothelioma is 20 to 40 years, patients are typically older adults in their sixth to ninth decade of life.[2]
Symptoms are usually related to the presence of intrathoracic disease and include shortness of breath;
dry, non-productive cough; and chest pain. Non-specific symptoms, such as fatigue, fever, sweats, and
weight loss, are also common. A history of abdominal distension and/or pain is more typical of primary
peritoneal mesothelioma, but may also denote intra-abdominal extension from advanced pleural disease.
Physical findings suggestive of a pleural effusion are typical. These include decreased breath sounds and
dullness to percussion on the affected side. Decreased breath sounds can also indicate trapped lung or
bronchial obstruction, both of which may be caused by malignant pleural mesothelioma.
Investigations
When mesothelioma is suspected, imaging studies should be obtained. A chest x-ray is an appropriate
initial test.[30] Possible findings include unilateral pleural effusion, pleural thickening, reduced lung
volumes, or parenchymal changes related to asbestos exposure (e.g., lower zone linear interstitial
fibrosis, pleural calcification). However, chest x-ray visualises the pleura poorly and will miss subtle
DIAGNOSIS
abnormalities. Therefore, when clinical suspicion is high, a computed tomography (CT) scan of the chest
and upper abdomen with intravenous contrast should also be obtained.[30] [31] Findings suggesting a
malignant process include circumferential or nodular pleural thickening or involvement of the mediastinal
pleura.[32] However, differentiating benign from malignant pleural abnormalities with CT alone is not
reliable.
The diagnosis of mesothelioma cannot be made from imaging studies alone. When imaging studies
confirm pleural effusion, with or without other pleural abnormalities, thoracentesis should be performed
to determine whether the fluid is a transudate or exudate, and to obtain pleural fluid for cytological
examination.[31] The sensitivity of cytology for mesothelioma is relatively low and often requires further
pathological assessment of biopsied tissues.[33]
The best study to evaluate the pleural lining of the lung and to obtain optimal biopsies is video-assisted
thoracoscopic surgery (VATS).[31] Biopsies of suspicious sites can confirm the diagnosis.
Chest x-ray demonstrating total left-sided collapse and replacement of

hemithorax with mesothelioma; there is reduced expansion on this side
From BMJ Case Reports 2011;doi:10.1136/bcr.09.2010.3319
DIAGNOSIS
7
Computed tomography scan of the lung showing a right-sided

pleural mesothelioma and left-sided calcified pleural plaque
From the collection of Dr Chris R. Kelsey; used with permission
DIAGNOSIS
Computed tomography scan of the mediastinum showing a right-

sided pleural mesothelioma and left-sided calcified pleural plaque
Immunohistochemistry is also recommended.[30] [31] This should use selected markers expected to be
positive in mesothelioma (e.g., calretinin, keratins 5/6, and nuclear WT1) as well as markers expected to
be negative in mesothelioma (e.g., CEA, EPCAM, claudin 4, TTF-1). Other markers can also be used to
help exclude differential diagnoses.[31]
Ancillary studies
Once a diagnosis of mesothelioma is made, additional tests may be necessary to guide management.
These include positron emission tomography scans to evaluate for regional or distant disease.[31] In
patients who are considered for surgical resection, pulmonary function tests, echocardiogram, and
mediastinoscopy are performed to assess cardiopulmonary function and to exclude metastases in the
paratracheal and subcarinal lymph nodes within the mediastinum. Routine blood work, including full blood
count and basic metabolic panel, is necessary to establish baseline function before treatment.
Positron emission tomography scan showing hypermetabolic right-sided pleural mesothelioma

History and exam

Key diagnostic factors
family history (common)
• Family history of mesothelioma and other cancers, including uveal melanoma, renal cell carcinoma,
and cutaneous melanoma, may suggest an underlying germline BAP1 mutation.[18] [19]
DIAGNOSIS
history of asbestos exposure (common)
• About 80% of patients have a history of asbestos exposure.[11] Occupational history regarding the
type of work performed (e.g., naval shipboard service; ship building; construction and maintenance;
vehicle brake mechanic; production of asbestos products such as cement, insulation, tiles, shingles,
gaskets, brakes, or textiles) may provide some clues.
age between 60 and 85 years (common)

• The latency period between exposure to asbestos and development of malignant pleural
mesothelioma is 20 to 40 years. Therefore, most patients are older adults.[2] [3]
shortness of breath (common)

• Increasing shortness of breath, typically due to a large pleural effusion or trapped lung, is the most
common symptom. Moderate or severe dyspnoea occurs in about 40% of patients.[34]
diminished breath sounds (common)

• Usually a result of pleural effusion, trapped lung, or bronchial obstruction.
dullness to percussion (common)
9
• Suggests presence of a pleural effusion on the affected side.
Other diagnostic factors

male sex (common)
• Male to female ratio in the US is 3:1, probably reflecting occupational exposure to asbestos.[2]
chest pain (common)

• Although mesothelioma does not commonly invade the chest wall, chest pain is a common symptom,
occurring in about 25% of patients.[34]
cough (common)
• Usually dry and non-productive.
constitutional symptoms (common)

• Include non-specific findings such as fatigue, fever, sweats, and weight loss.
• Moderate or severe fatigue occurs in about 30% of patients.[34]
abdominal distension and/or pain (uncommon)

• Uncommon, but can occur as a consequence of extension to the abdominal cavity with resultant
ascites; often a late presentation of disease. It is more often seen as a presenting symptom of
peritoneal mesothelioma.
Risk factors
Strong
asbestos exposure
• Considered the principal risk factor for developing malignant pleural mesothelioma. This association
DIAGNOSIS
was first reported in 1960 among patients working in the vicinity of South African asbestos mines and
has since been confirmed by innumerable epidemiological studies.[24] [25]
• In clinical studies, about 80% of patients with malignant pleural mesothelioma have a history of
asbestos exposure.[11] Occupational history regarding the type of work performed (e.g., naval
shipboard service; ship building; construction and maintenance; vehicle brake mechanic; production of
asbestos products such as cement, insulation, tiles, shingles, gaskets, brakes, or textiles) may provide
some clues.
• There are three main types of asbestos: chrysotile (white asbestos), amosite (brown asbestos), and
crocidolite (blue asbestos). Crocidolite, which is composed of long and narrow fibres, seems to be the
primary type of asbestos associated with the development of mesothelioma.[26] The mechanism of
carcinogenesis is not known with certainty.
age 60 to 85 years
• The latency period between exposure to asbestos and development of malignant pleural
mesothelioma is 20 to 40 years, and therefore most patients are older adults.[2] [3]
Weak
asbestos exposure during home maintenance and renovation
• There is an increasing incidence of mesothelioma in people who have been exposed to asbestos
during home maintenance and renovation.[27]
male sex
• Males are significantly more affected than females, likely reflecting occupational exposure to
asbestos.[2]
radiation exposure
• Radiation is a known carcinogen and has been shown to increase the risk of many types of cancer.
Case reports and epidemiological studies have suggested that radiation exposure is associated
with the development of mesothelioma.[15] This includes patients treated with radiotherapy for other
malignancies or benign conditions, as well as patients treated with the contrast medium thorotrast,
which contains radioactive thorium dioxide. Patients with radiation-associated mesothelioma tend to be
younger than patients with asbestos-associated mesothelioma.[28]
genetic predisposition
• Germline mutations in the gene encoding BRCA1 associated protein-1 (BAP1) can predispose
carriers to mesothelioma.[23] Other cancers, in particular uveal and cutaneous melanomas, basal cell
carcinomas, and renal cell carcinomas, have been described in these individuals.[18] [19]
simian virus 40 (SV-40)

• The oncogenic DNA simian virus 40 (SV-40) has been detected in human mesotheliomas and can
induce mesothelioma-like tumours in rodents. What role, if any, SV-40 plays in the pathogenesis of
malignant pleural mesothelioma is unclear.[17]
DIAGNOSIS
11
Investigations
1st test to order
Test Result
chest x-ray unilateral pleural
effusion, irregular pleural
• An appropriate initial test.[30] However, chest x-ray visualises the
pleura poorly and will miss subtle abnormalities. Furthermore, it does thickening, reduced
lung volumes, and/or
not assess the mediastinal lymph nodes.
parenchymal changes
related to asbestos
exposure (e.g., lower zone
linear interstitial fibrosis)
Chest x-ray demonstrating total left-sided collapse and replacement of

hemithorax with mesothelioma; there is reduced expansion on this side
DIAGNOSIS
CT scan of the chest and upper abdomen with intravenous pleural thickening and/or
contrast discrete pleural plaques,
pleural and/or pericardial
• A more sensitive modality than chest x-ray, providing more detail of
effusions; enlarged hilar
the pleura, lungs, and mediastinum. However, differentiating benign
and/or mediastinal lymph
from malignant pleural processes with CT alone can be difficult.
nodes; chest wall invasion
Findings suggesting a malignant process include circumferential or
and/or spread along
nodular pleural thickening, involvement of the mediastinal pleura, or
needle tracts can occur
enlarged regional lymph nodes.[32]
Test Result
Computed tomography scan of the lung showing a right-sided

pleural mesothelioma and left-sided calcified pleural plaque
DIAGNOSIS
Computed tomography scan of the mediastinum showing a right-
sided pleural mesothelioma and left-sided calcified pleural plaque
13
Other tests to consider
Test Result
thoracentesis exudate; may show
malignant cells within the
• The sensitivity of cytology for mesothelioma is relatively low and
pleural fluid
typically requires further pathological assessments.[33]
pleural biopsy specimen for pathological
diagnosis
• Pathological confirmation of malignancy can be obtained with pleural
fluid cytology, obtained via transthoracic needle aspiration biopsy
(typically using CT guidance), but is not as reliable for diagnosis
as a tissue core specimen. Pleural biopsies performed during
VATS exploration is the most invasive but also the most accurate
modality.[35]
video-assisted thoracoscopic surgery (VATS) pleural thickening
or discrete plaques;
• Regarded as the best study to evaluate the pleural lining of the lung
lymphadenopathy
and to obtain optimal biopsy specimens for histology.[31]
immunohistochemistry positive results for
certain markers (e.g.,
• Immunohistochemistry is also recommended.[30] [31] This should
calretinin, keratins 5/6,
use selected markers expected to be positive in mesothelioma
and nuclear WT1) make
(e.g., calretinin, keratins 5/6, and nuclear WT1) as well as markers
expected to be negative in mesothelioma (e.g., CEA, EPCAM, claudin mesothelioma more likely,
4, TTF-1). Other markers can also be used to help exclude differential while positive results for
other markers (e.g., CEA,
diagnoses.[31]
EPCAM, claudin 4, TTF-1)
make mesothelioma less
likely
chest MRI degree of tumour

extension, especially
• MRI has the potential to differentiate between benign fibrous
to the chest wall and
mesothelioma (low signal intensity on T2-weighted images) and
malignant mesothelioma (high signal intensity), but it is not as reliable diaphragm
as biopsy and will seldom alter management.
DIAGNOSIS
PET scan further evaluates location

• PET has the potential to distinguish benign pleural abnormalities from and extent of primary
tumour; evaluates for
malignant processes.[36]
distant metastases
• PET can help define the extent of intrathoracic and mediastinal
disease and detect regional and distant metastases.[31]
Positron emission tomography scan showing

hypermetabolic right-sided pleural mesothelioma
Test Result
cervical mediastinoscopy spread to mediastinal
lymph nodes
• Mediastinal (N2) lymph node involvement is a poor prognostic
factor, and such patients are not ideal candidates for aggressive
multimodality therapy.[37]
• Mediastinoscopy, especially in patients with abnormal lymph nodes
on CT scan or PET, should be considered before surgery.
pulmonary function tests spirometry and lung
volumes
• FEV1 and diffusion capacity of lung for carbon monoxide (DLCO)
should be performed on all patients with mesothelioma who are being
evaluated for surgery. Patients with marginal function can be further
assessed with radionuclide studies as needed.
• In general, postoperative FEV1 and DLCO should be >40% of
predicted values.
• Spirometry is a sensitive predictor of postoperative complications
after thoracotomy.
FBC usually normal; low
haemoglobin, high
• Baseline blood counts are necessary before treatment is initiated or
platelet count, high white
invasive procedures are performed.
blood cell count are
• Chemotherapy, and to a lesser degree radiotherapy, can decrease
haematopoiesis, necessitating baseline and periodic analysis of usually found in advanced
disease and are poor
blood counts.
prognostic factors
basic metabolic panel usually normal

• Recommended as baseline before treatment is initiated.
• Some chemotherapy agents, cisplatin in particular, can affect
electrolytes and kidney function.
DIAGNOSIS
15
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Benign reactive • Can be caused by several • Pleural biopsy is necessary
mesothelial hyperplasia different processes; to distinguish benign
therefore, a history of mesothelial hyperplasia
infection, pulmonary from malignant pleural
infarcts, drug reactions, mesothelioma; invasion of
collagen vascular diseases, underlying tissues favours
trauma, or surgery may be mesothelioma.[38]
present.[38]
Benign asbestos-related • Exposure to asbestos can • Pleural plaques are

pleural reactions cause several benign pleural frequently documented on
reactions, including pleural plain chest x-ray, but CT
effusion, pleural plaques, is more sensitive for their
diffuse pleural fibrosis, and detection. Slow progression
rounded atelectasis.[9] of plaques is typical. The
Differentiating these presence of plaques is
processes from malignant associated with a greater risk
pleural mesothelioma can be of mesothelioma, but this
difficult. is thought to be related to
greater exposure or retained
body burden, not malignant
degeneration.[39]
• Findings on chest CT scan
(serial studies usually
necessary) suggesting
a malignant process
include circumferential or
nodular pleural thickening,
involvement of the
mediastinal pleura, or
DIAGNOSIS
enlarged regional lymph

nodes.[32]
Non-small cell lung • Typical features include • Chest CT scan shows

cancer cough, haemoptysis, size, location, and extent
chest pain, dyspnoea, and of primary tumour, which
hoarseness (if recurrent is more often within lung
laryngeal nerve paralysis). parenchyma rather than
• Patients frequently look pleural; evaluates for
unwell and are short hilar and/or mediastinal
of breath, with signs of lymphadenopathy and
recent weight loss. Finger distant metastases.
clubbing and hypertrophic • Depending on the location of
osteoarthropathy may be the tumour, bronchoscopic-
present. or CT-guided biopsy
• A significant history of provides pathological
smoking or asbestos confirmation of diagnosis.
exposure suggests that a
primary lung neoplasm be
strongly considered.
Condition Differentiating signs / Differentiating tests

symptoms
Small cell lung cancer • Typical features include • Chest CT scan shows
cough, haemoptysis, massive lymphadenopathy
chest pain, dyspnoea, and and direct mediastinal
hoarseness (if recurrent invasion.
laryngeal nerve paralysis). • Depending on the location of
• Patients frequently look the tumour, bronchoscopic-
unwell and are short of or CT-guided biopsy
breath with signs of recent provides pathological
weight loss. confirmation of diagnosis.
• Finger clubbing
and hypertrophic
osteoarthropathy may be
present.
• A significant history of
smoking or asbestos
exposure suggests that a
primary lung neoplasm be
strongly considered.
• Usually, wheezing from
underlying chronic
obstructive pulmonary
disease (COPD) or bronchial
obstruction, rales due to
post-obstructive pneumonia
or atelectasis, or diminished
breath sounds from bronchial
obstruction are present
unless early disease.
Metastatic cancer • Symptoms will relate to • Chest CT scan shows

the site of the primary one or multiple nodules of
tumour, and there may be variable sizes from diffuse
general symptoms of pain, micronodular shadows
DIAGNOSIS
weight loss, malaise, cough, (miliary) to well-defined
dyspnoea, clubbing, and masses. Pleural tissue
focal wheezing. thickening is rare.
• Physical findings may or may • Flexible bronchoscopy and
not be present depending on biopsy shows characteristic
nature and stage of tumour. malignant cells.
Criteria
International staging system for diffuse malignant pleural
mesothelioma[40] [41]
Developed by the International Mesothelioma Interest Group (IMIG), and adopted by the American Joint
Committee on Cancer, this staging system accurately correlates prognosis with disease burden, but is
complex and cumbersome. It describes the extent of disease based on the following anatomic factors: size
and extent of the primary tumour (T); regional lymph node involvement (N); and presence or absence of
distant metastases (M).
17
Mesothelioma Management
Approach
There is no standard therapy for malignant pleural mesothelioma. As for many rare tumours, few prospective
studies have been conducted evaluating differing treatment approaches. Therapy must be individualised
based on the stage of disease at presentation, histology, and general health of the patient.
Surgery
Two distinct surgical approaches are commonly used to definitively treat the primary tumour: extra-pleural
pneumonectomy (EPP) and pleurectomy with decortication.[31] However, surgery alone is rarely curative
and is usually employed in the setting of multimodality therapy involving chemotherapy with or without
radiation. Overall survival at 2 years was 18.8% in a retrospective review of 394 patients with malignant
pleural mesothelioma between 1989 and 2003.[42] Twenty-seven patients (6.8%) in this group underwent
surgical resection (extra-pleural pneumonectomy 15, pleurectomy/decortication 12) followed by adjuvant
therapy. However, given the small numbers in trials, the effect of surgery on long-term survival remains
unclear.[42] [43]
EPP removes the parietal and visceral pleura, ipsilateral lung and pericardium, and the hemidiaphragm
en bloc. Pleurectomy with decortication is a more limited procedure involving removal of the parietal
pleura from the chest wall, mediastinum, pericardium, and diaphragm, as well as removal of the visceral
pleura from the ipsilateral lung (decortication). The ipsilateral lung remains intact. The superiority of EPP
over pleurectomy with decortication has not been demonstrated, but EPP does facilitate postoperative
radiotherapy, which seems to decrease the risk of local recurrence.[43] [44] [45] [46] However, the risk of
developing a complication after EPP is high, even in experienced centres.[44] EPP is most appropriate
for patients with epithelioid histology, no lymph node involvement, and sufficient cardiac and pulmonary
reserve. Surgery does not confer a significant survival benefit in sarcomatoid mesothelioma.
Chemotherapy
In patients with potentially resectable malignant pleural mesothelioma, chemotherapy can be given
preoperatively to facilitate resection and improve survival. Most studies have used cisplatin-based
doublets with response rates of about 30%, with about 75% of patients subsequently undergoing EPP.[37]
[47] [48] [49] Similarly, in patients who have undergone EPP, adjuvant cisplatin-based chemotherapy is
often given.
In patients with inoperable or recurrent mesothelioma, chemotherapy is often given in an attempt to

improve quality of life and survival. A randomised study compared chemotherapy with active symptom
control and found no difference in overall survival or quality of life.[34] However, two earlier randomised
studies demonstrated a survival benefit with cisplatin combined with an antifolate when compared with
cisplatin alone.[50] [51] In particular, pemetrexed plus cisplatin has been shown to significantly increase
the length of survival and relieve symptoms in patients with inoperable mesothelioma, when compared
with cisplatin alone.[52] Therefore, in appropriate patients with good performance status (measures how
well a patient is able to carry out daily activities), recommended first-line chemotherapy is cisplatin and
pemetrexed,[31] given every 21 days. Vitamin supplementation, particularly B12 and folic acid, should be
MANAGEMENT
added to reduce the risk of haematological toxicity associated with pemetrexed.
Cisplatin is associated with nephrotoxicity, nausea, and vomiting. Carboplatin is often substituted for
cisplatin based on its favourable safety profile and ease of administration.[31] Although trials comparing
cisplatin and carboplatin are not available, based on single-arm phase II trials, the efficacy is similar.[53]
A phase III trial showed significant improvements in survival in patients with unresectable pleural
mesothelioma when bevacizumab was combined with chemotherapy (pemetrexed and cisplatin)
compared with chemotherapy alone.[54] Bevacizumab is not recommended for patients with performance
status >2, substantial cardiovascular comorbidity, uncontrolled hypertension, age >75 years, bleeding or
clotting risk or other contraindications to bevacizumab. There is insufficient data to recommend adding
bevacizumab to carboplatin plus pemetrexed.
There is no standard second-line chemotherapy in malignant pleural mesothelioma, although several

drugs and drug combinations have been explored.[55] [56] [57] If pemetrexed was not given in the first-
line setting, it should be considered in the second-line setting, alone or in combination with a platinum
agent.[58] In patients for whom clinical trials are not an option, vinorelbine may be offered as second-line
therapy.[31]
Radiotherapy
Post-extrapleural pneumonectomy radiotherapy (RT) to the ipsilateral chest cavity and chest wall can
be used as adjuvant therapy,[31] or to relieve symptoms arising from local/regional growth of tumour.
Comprehensive RT after pleurectomy with decortication is generally not recommended due to risk of
radiation pneumonitis.[31] Even with moderate postoperative doses of RT the risk of local failure remains
high and, because the ipsilateral lung remains intact, the risk of radiation pneumonitis is prohibitive.[59]
[60] Improved radiation delivery techniques, such as intensity-modulated radiotherapy (IMRT) may allow
delivery of adequate doses to target structures while minimising the risk of radiation pneumonitis.[61]
The role of RT after extra-pleural pneumonectomy (EPP) is controversial. The risk of local failure remains
high after EPP alone, and using RT to decrease this risk is rational.[43] Indeed, preliminary studies
have shown promising rates of local control after EPP and RT using intensity-modulated techniques.[37]
[62] However, care must be taken to limit dosage to the contralateral lung, given the possibility of lethal
pulmonary injury.[63] A trial of high-dose hemithoracic RT after neoadjuvant chemotherapy and EPP
did not show a significant improvement in locoregional relapse-free survival in patients who received
postoperative RT.[64] However, this study was methodologically flawed.
RT can also be used to palliate local sites of disease that may be causing distressing symptoms, most
commonly pain due to chest wall invasion or shortness of breath due to airway obstruction. Whether
an abbreviated course of RT to decrease malignant seeding after invasive diagnostic procedures is
efficacious is not clear.[65] [66] [67] A systematic review suggests that prophylactic irradiation therapy
after video-assisted thoracoscopic surgery is not justified.[68] One study of prophylactic RT to prevent
procedure-tract metastases after large-bore pleural interventions found no significant difference was seen
in the incidence of procedure-tract metastases in the immediate and deferred RT groups.[69]
Inoperable or recurrent disease: palliative procedures

Thoracentesis and pleurodesis may provide symptomatic relief. In addition to aiding diagnosis,
thoracentesis can often provide temporary relief for those patients suffering from dyspnoea as a
consequence of a large pleural effusion. Pleurodesis, defined as the artificial obliteration of the pleural
space, can be performed to prevent re-accumulation of pleural fluid. Talc pleurodesis seems to be
MANAGEMENT
the most effective sclerosant.[70] Video-assisted thoracoscopic surgery (VATS) pleurodesis provides
optimal results.[70] One randomised study showed that VATS partial pleurectomy was not superior to talc
pleurodesis in terms of improving survival or symptom control.[71]
19
Certain palliative interventions may help improve symptoms, psychological functioning, and quality of life.
Some examples include nursing programmes, interventions to manage breathlessness, counselling, as
well as psychotherapeutic, psychosocial, and educational interventions.[72]
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Acute ( summary )
operable disease
1st surgery
plus pre- and/or postoperative chemotherapy
adjunct radiotherapy
inoperable or recurrent disease
1st chemotherapy
adjunct palliative procedures + supportive care

MANAGEMENT
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
MANAGEMENT
21
Acute
operable disease
1st surgery
» Two distinct surgical approaches are

commonly used to definitively treat the primary
tumour: that is, extra-pleural pneumonectomy
(EPP) and pleurectomy with decortication.[31]
However, surgery is rarely curative, and the
effect on long-term survival remains unclear.[43]
» EPP removes the parietal and visceral

pleura, ipsilateral lung and pericardium, and the
hemidiaphragm en bloc.
» Pleurectomy with decortication is a more

limited procedure involving removal of the
parietal pleura from the chest wall, mediastinum,
pericardium, and diaphragm, as well as removal
of the visceral pleura from the ipsilateral lung
(decortication). The ipsilateral lung remains
intact.
» The superiority of EPP over pleurectomy with

decortication has not been demonstrated, but
EPP does facilitate postoperative radiotherapy,
which seems to decrease the risk of local
recurrence.[43] [44] [45] However, the risk of
developing a complication after EPP is high,
even in experienced centres.[44] EPP is most
appropriate for patients with epithelioid histology,
no lymph node involvement, and sufficient
cardiac and pulmonary reserve.
plus pre- and/or postoperative chemotherapy
Treatment recommended for ALL patients in
selected patient group
Primary options
» cisplatin
-and-
» pemetrexed
-and-
» cyanocobalamin: 1 mg intramuscularly as
a single dose one week prior to first dose
of pemetrexed and then every 9 weeks
thereafter
-and-
» folic acid: 400-1000 micrograms orally
once daily for 7 days prior to the first dose
of pemetrexed, during treatment, and for 21
MANAGEMENT
days after the last dose
» In patients with potentially resectable

malignant pleural mesothelioma, chemotherapy
can be given preoperatively to facilitate
resection and improve survival. Most studies
Acute
have used cisplatin-based doublets with
response rates of about 30%, with about 75% of
patients subsequently undergoing extra-pleural
pneumonectomy (EPP).[37] [47] [48] [49]
» Similarly, in patients who have undergone EPP,

adjuvant cisplatin-based chemotherapy is often
administered.
» Vitamin supplementation, particularly B12

(also known as cyanocobalamin) and folic
acid, should be added to reduce the risk
of haematological toxicity associated with
pemetrexed.
» See local specialist protocol for dosing

guidelines.
Treatment recommended for SOME patients in
» Post-extrapleural pneumonectomy
radiotherapy (RT) to the ipsilateral chest
cavity and chest wall can be used as adjuvant
therapy,[31] or to relieve symptoms arising from
local/regional growth of tumour.
» The role of RT after extra-pleural

pneumonectomy (EPP) is controversial. The
risk of local failure remains high after EPP
alone, and using RT to decrease this risk
is rational.[43] Indeed, preliminary studies
have shown promising rates of local control
after EPP and RT using intensity-modulated
techniques.[37] [62] However, care must be
taken to limit dose to the contralateral lung, given
the possibility of lethal pulmonary injury.[63]
» Comprehensive RT after pleurectomy with

decortication is not recommended. Even with
moderate postoperative doses of RT the risk
of local failure remains high and, because
the ipsilateral lung remains intact, the risk of
radiation pneumonitis is prohibitive.[59] [60]
inoperable or recurrent disease
1st chemotherapy
Primary options
» cisplatin
MANAGEMENT
-or-
» carboplatin
--AND--
» pemetrexed
--AND--
23
Acute
thereafter
--AND--
OR
» cisplatin
-and-
» pemetrexed
-and-
» bevacizumab
-and-
thereafter
-and-
Secondary options
» vinorelbine
» In patients with inoperable or recurrent

mesothelioma, chemotherapy is often given in an
attempt to improve quality of life and survival.
» A randomised study compared chemotherapy

with active symptom control and found
no difference in overall survival or quality
of life.[34] However, 2 earlier randomised
studies demonstrated a survival benefit with
cisplatin combined with an antifolate compared
with cisplatin alone.[50] [51] In particular,
pemetrexed plus cisplatin has been shown
to increase significantly the length of survival
and to relieve symptoms in patients with
inoperable mesothelioma, when compared
with cisplatin alone.[52] Treatment with vitamin
supplementation - folic acid and vitamin B12
(also known as cyanocobalamin) - decreased the
risk of haematological toxicity associated with
MANAGEMENT
pemetrexed.
» Therefore, in appropriate patients with good

performance status, the recommended first-line
chemotherapy is cisplatin and pemetrexed[31]
given every 21 days. Vitamin supplementation,
Acute
particularly B12 and folic acid, should be added
to reduce the risk of haematological toxicity.
» Cisplatin is associated with nephrotoxicity,

nausea, and vomiting. Carboplatin is often
substituted for cisplatin based on its favourable
safety profile and ease of administration.[31]
Although trials comparing cisplatin and
carboplatin are not available, based on single-
arm phase II trials, the efficacy is similar.[53]
» Bevacizumab may be added to cisplatin plus

pemetrexed in selected patients. Bevacizumab is
not recommended for patients with performance
status >2, substantial cardiovascular
comorbidity, uncontrolled hypertension, age
>75 years, bleeding or clotting risk, or other
contraindications to bevacizumab.[54]
» In patients for whom clinical trials are not an

option, vinorelbine may be offered as second-
line therapy.[31]
» See local specialist protocol for dosing

guidelines.
» Radiotherapy can also be used to palliate local
sites of disease that may be causing distressing
symptoms, most commonly pain due to chest
wall invasion or shortness of breath due to
airway obstruction.
adjunct palliative procedures + supportive care
» Therapeutic thoracentesis and pleurodesis
may provide symptomatic relief.
» In addition to aiding diagnosis, thoracentesis

can often provide temporary relief for those
patients suffering from dyspnoea as a
consequence of a large pleural effusion.
» Pleurodesis, defined as the artificial

obliteration of the pleural space, can be
performed to prevent re-accumulation of
pleuritic fluid. Talc pleurodesis seems to be the
most effective sclerosant.[70] Video-assisted
MANAGEMENT
thoracoscopic surgery (VATS) pleurodesis

provides optimal results.[70] One randomised
study showed that VATS partial pleurectomy
was not superior to talc pleurodesis in terms of
improving survival or symptom control.[71]
25
Acute
» Certain interventions may help to improve
symptoms, psychological functioning, and
quality of life. Some examples include nursing
programmes, interventions to manage
breathlessness, and counselling, as well
as psychotherapeutic, psychosocial, and
educational interventions.[72]
MANAGEMENT
Emerging
Targeted immunotherapy
Immune checkpoints (e.g., programmed death-1 [PD-1], cytotoxic T-lymphocyte antigen-4 [CTLA-4]) are
required for protecting the normal tissues from immune attack by curbing the effector T-cell responses.
Nivolumab is a monoclonal antibody that blocks the binding of PD-1 on T cells with its ligands on immune
and tumour cells, allowing for immune-mediated attack of cancer cells. Ipilimumab is a monoclonal antibody
which binds to CTLA-4. Nivolumab plus ipilimumab is approved in the US and Europe as a first-line treatment
option for adults with unresectable malignant pleural mesothelioma. In the pivotal CheckMate 743 study,
nivolumab plus ipilimumab was compared to standard-of-care chemotherapy in 605 patients with inoperable
untreated malignant pleural mesothelioma.[73] Nivolumab plus ipilimumab provided significant and clinically
meaningful improvements in overall survival versus standard-of-care chemotherapy (pemetrexed, given in
combination with either cisplatin or carboplatin). After a median follow-up of 29.7 months, nivolumab plus
ipilimumab significantly extended overall survival versus chemotherapy (median overall survival 18.1 months
vs. 14.1 months). Two-year overall survival rates were 41% in the nivolumab plus ipilimumab group and 27%
in the chemotherapy group.[73]
Kinase inhibitors
Numerous phase II trials have shown the lack of efficacy of inhibitors targeting oncogenic kinases in pleural
mesothelioma. These agents include gefitinib, erlotinib, imatinib, sunitinib, sorafenib, dasatinib, vatalanib,
and semaxanib, to name only a few. These results are hardly surprising given the genomic landscape of
pleural mesothelioma, which consists largely of alterations in tumour suppressor genes such as BAP1, NF2,
and CDKN2A.[23]
Anti-antigen therapies
Immunotherapies targeting antigens that are differentially overexpressed in mesothelioma compared with
normal tissue is another area of active investigation. Transcription factor, WT1, and tumour differentiation
antigen, mesothelin, are particularly promising in this regard. Mesothelin-targeted interventions that are in
clinical trials include an antibody, antibody drug conjugates, vaccine, immunotoxins, and chimeric antigen
receptor (CAR) T cells.
Intrapleural chemotherapy
Intrapleural therapy would seem a promising method to deliver anti-neoplastic agents because they
potentially treat the entire at-risk area of the hemithorax and lung. Intrapleural interventions that are under
investigation include chemotherapies, photodynamic therapy, anti-mesothelin CAR T cells, oncolytic measles
viruses, and gene therapy with tumour selective adenoviruses.
Primary prevention
Elimination of asbestos exposure through substitution with other materials will significantly decrease the risk
of developing asbestosis and pleural-related changes, including malignant pleural mesothelioma. Legislation
regarding asbestos elimination from the workplace is in place in many countries, and in the US (where
regulations were implemented in 1972) it may partially account for the flat or slightly declining incidence of
mesothelioma.
MANAGEMENT
Minimisation of exposure through engineering controls (i.e., enclosing work process or exhaust hoods) is the
next best approach, after substitution, to reducing the risk of disease. Respirators with high protection factors
(i.e., positive pressure or full face mask) are used for work where the location and conditions vary, such as
construction. Provision to ensure that asbestos is not tracked home, such as laundering work clothes at work
27
and lockers for clean (street) and dirty (work) clothes separated by a shower, are required to reduce asbestos
exposure to workers' family members.
There is a need for research in the chemoprevention of asbestos exposure.[29]
Secondary prevention
Smoking cessation should be encouraged to limit further deterioration in lung function. Immunisations to
prevent pulmonary infections, such as influenza, are appropriate.
Patient discussions
Patients are encouraged to progressively increase their activity after completing therapy. Smoking
cessation is strongly advised in order to limit further deterioration in lung function.
MANAGEMENT
Mesothelioma Follow up
Monitoring
Monitoring
FOLLOW UP
After definitive treatment for malignant pleural mesothelioma, often consisting of surgery, radiotherapy,
and chemotherapy, patients should be monitored closely for treatment-related toxicity, such as post-
thoracotomy pain, radiation pneumonitis, and chemotherapy-induced haematological toxicity. Similarly,
patients with inoperable or recurrent disease who have completed a course of chemotherapy should also
be monitored closely to evaluate for cytopenias, renal damage, neuropathy, and other adverse treatment
affects.
After completing therapy, patients are usually reviewed every 3 to 6 months. In the absence of concerning
symptoms or signs, more frequent follow-up imaging is probably of little value, and therefore, not routinely
recommended.
29
Complications
Complications Timeframe Likelihood

FOLLOW UP
surgical morbidity short term high
The risk of developing a complication after extra-pleural pneumonectomy is high, even in experienced
centres.[44] Common complications include atrial fibrillation, prolonged intubation, vocal cord paralysis,
and deep vein thrombosis.
Fewer complications have been noted after pleurectomy with decortication.
acute radiation morbidity short term high
Patients can develop several adverse effects during radiotherapy, including erythema of the skin,
increased pain along a thoracotomy scar, odynophagia as a result of oesophagitis, nausea and vomiting,
and fatigue.
radiation pneumonitis short term medium
After extra-pleural pneumonectomy, excessive radiation dose to the contralateral lung can lead to radiation
pneumonitis, a condition characterised by shortness of breath, dry cough, and low-grade fevers occurring
1 to 6 months after completing radiotherapy.
Severe cases can be fatal.[63] The incidence of fatal pulmonary toxicity after radiotherapy (intensity-
modulated radiotherapy) has varied between 10% and 46% and is closely related with dose volume
parameters.[63] [74] [75] Restricting the dose to the contralateral lung is imperative.
Corticosteroids, usually prednisone, are the mainstay of treatment.
Radiotherapy after pleurectomy with decortications is not recommended, in part due to high rates of
radiation pneumonitis.[59]
chemotherapy-induced haematological toxicity short term medium
Haematological toxicity is the most common adverse effect from treatment with cisplatin and pemetrexed,
particularly if vitamin supplementation is not given (B12 and folic acid).[51]
postoperative mortality short term low
The incidence of postoperative mortality after extra-pleural pneumonectomy (EPP) ranges from 4% to
15% at 30 days post-surgery, whereas the incidence of postoperative mortality after pleurectomy with
decortication is about 4% 30 days post-surgery.[43] [44] [45]
Pulmonary embolism is the most common cause of operative mortality.[44]
Given the complexity of EPP, this procedure should be performed by experienced surgeons in hospitals
that are equipped to manage the many complications that can develop.[44]
local invasion of crucial thoracic structures variable low
Patients with inoperable or recurrent disease have a high risk of local disease progression, as do
patients with operable disease treated with surgery alone. Consequently, dysphagia, hoarseness, cord
compression, brachial plexopathy, Horner's syndrome, and superior vena cava syndrome can occur.
Complications Timeframe Likelihood

distant metastases variable low
FOLLOW UP
Metastases to the opposite lung, brain, and abdominal cavity may occur. Other extra-thoracic sites can
also be affected.
If extension to the abdominal cavity occurs, ascites can develop with consequent abdominal distension
and/or pain.
Prognosis
Despite advances in treatment, malignant pleural mesothelioma remains a highly lethal malignancy. Overall,
the median survival is 10 to 15 months, with only 5% to 10% of patients alive 5 years after diagnosis.[37] [62]
Operable disease
With surgery alone, the risk of local disease progression within the chest is high. The risk of local failure after
extra-pleural pneumonectomy (EPP) plus radiotherapy seems to be lower, with more patients developing
distant metastases.[62]
Long-term survival is greatest for patients with epithelioid histology without mediastinal lymph node
involvement who complete multimodality therapy. However, even this subgroup is at high risk of recurrence
and death.[37] [62] The outlook is much worse for patients with sarcomatoid histology, mediastinal
lymph node involvement, or failure to complete multimodality therapy, which is often due to early disease
progression.[37] [62]
Inoperable or recurrent disease

In patients with unresectable malignant pleural mesothelioma, median survival with optimal chemotherapy is
about 12.3 months, but progression and death is inevitable.[51] Local disease progression can lead to chest
pain, dyspnoea, dysphagia, and, eventually, failure to thrive. Distant metastases are also common, causing
site-specific symptoms.
31
Mesothelioma Guidelines
Diagnostic guidelines
United Kingdom
BTS guideline for the investigation and management of malignant pleural

mesothelioma (ht tps://www.brit-thoracic.org.uk/quality-improvement/
guidelines)
Published by: British Thoracic Society Last published: 2018
Europe
Malignant pleural mesothelioma (ht tps://www.esmo.org/Guidelines/Lung-and-

Chest-Tumours)
Published by: European Society for Medical Oncology Last published: 2015
GUIDELINES
North America
NCCN clinical practice guidelines in oncology: malignant pleural

mesothelioma (ht tps://www.nccn.org/professionals/physician_gls/
default.aspx)
Published by: National Comprehensive Cancer Network Last published: 2021
Treatment guidelines
United Kingdom
BTS guideline for the investigation and management of malignant pleural

mesothelioma (ht tps://www.brit-thoracic.org.uk/quality-improvement/
guidelines)
Published by: British Thoracic Society Last published: 2018
Pemetrexed for the treatment of malignant pleural mesothelioma (ht tps://

www.nice.org.uk/guidance/ta135)
Published by: National Institute for Health and Care Excellence Last published: 2008
Mesothelioma Guidelines
Europe
Malignant pleural mesothelioma (ht tps://www.esmo.org/Guidelines/Lung-and-

Chest-Tumours)
Published by: European Society for Medical Oncology Last published: 2015
Guidelines for the management of malignant pleural mesothelioma (ht tps://

www.ers-education.org/guidelines.aspx)
Published by: European Respiratory Society; European Society of Last published: 2010
Thoracic Surgeons
North America
NCCN clinical practice guidelines in oncology: malignant pleural

mesothelioma (ht tps://www.nccn.org/professionals/physician_gls/
default.aspx)
GUIDELINES
Published by: National Comprehensive Cancer Network Last published: 2021
Treatment of malignant pleural mesothelioma (ht tps://www.asco.org/practice-

guidelines/quality-guidelines/guidelines/thoracic-cancer)
Published by: American Society of Clinical Oncology Last published: 2018
33
Mesothelioma References
Key articles
• arbone M, Ly BH, Dodson RF, et al. Malignant mesothelioma: facts, myths, and hypotheses. J Cell
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• Neri M, Ugolini D, Boccia S, et al. Chemoprevention of asbestos-linked cancers: a systematic review.

Anticancer Res. 2012 Mar;32(3):1005-13. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22399624?
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• Rusch VW, Piantadosi S, Holmes EC. The role of extrapleural pneumonectomy in malignant pleural
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• Flores RM, Pass HI, Seshan VE, et al. Extrapleural pneumonectomy versus pleurectomy/decortication
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pubmed/18329481?tool=bestpractice.bmj.com)
• Green J, Dundar Y, Dodd S, et al. Pemetrexed disodium in combination with cisplatin versus other
cytotoxic agents or supportive care for the treatment of malignant pleural mesothelioma. Cochrane
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• Nagendran M, Pallis A, Patel K, et al. Should all patients who have mesothelioma diagnosed by video-
assisted thoracoscopic surgery have their intervention sites irradiated? Interact Cardiovasc Thorac
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• Rueda JR, Solà I, Pascual A, et al. Non-invasive interventions for improving well-being and quality of
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41
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Mesothelioma Images
Images
IMAGES
Figure 1: Chest x-ray demonstrating total left-sided collapse and replacement of hemithorax with
mesothelioma; there is reduced expansion on this side
43
IMAGES Mesothelioma Images
Figure 2: Computed tomography scan of the lung showing a right-sided pleural mesothelioma and left-sided
calcified pleural plaque
Figure 3: Computed tomography scan of the mediastinum showing a right-sided pleural mesothelioma and
left-sided calcified pleural plaque
Mesothelioma Images
Figure 4: Positron emission tomography scan showing hypermetabolic right-sided pleural mesothelioma
IMAGES
45
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Contributors:
// Authors:
Anish Thomas, MD, MBBS

Staff Clinician
Center for Cancer Research, Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute,
Bethesda, MD
DISCLOSURES: AT declares that he has no competing interests.
Jaydira del Rivero, MD

Medical Oncology Branch
Center for Cancer Research, National Cancer Institute, Bethesda, MD
DISCLOSURES: JdR declares that he has no competing interests.
Mary Hesdorffer, MS, APRN

Nurse Practitioner
Executive Director, Mesothelioma Applied Research Foundation, Alexandria, VA
DISCLOSURES: MH declares that she has no competing interests.
// Acknowledgements:
Dr Anish Thomas, Dr Jaydira del Rivero, and Mrs Mary Hesdorffer would like to gratefully acknowledge Dr
Robert Taub and Dr Chris R. Kelsey, the previous contributors to this topic.
DISCLOSURES: RT and CRK declare that they have no competing interests.
// Peer Reviewers:
Marc de Perrot, MD, MSc

Associate Professor of Surgery
University of Toronto, Division of Thoracic Surgery, Toronto General Hospital, Ontario, Canada
DISCLOSURES: MdP is an author of a reference cited in this topic.
Nicholas J. Vogelzang, MD
Chair and Medical Director
Developmental Therapeutics, Co-Chair, GU Committee, US Oncology Research, Comprehensive Cancer
Centers of Nevada, Las Vegas, NV
DISCLOSURES: NJV is a past chair of a US-based mesothelioma foundation. NJV is an author of a number
of references cited in this topic.
Tom Treasure, MD, MS FRCS, FRCP

Professor of Cardiothoracic Surgery (Honorary)
Clinical Operational Research Unit, Department of Mathematics, University College London, London, UK
DISCLOSURES: TT declares that he has no competing interests.

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Mesothelioma

Straight to the point of care

Last updated: Nov 04, 2021

Common histological subtypes

Chest x-ray demonstrating total left-sided collapse and replacement of

Computed tomography scan of the lung showing a right-sided

Computed tomography scan of the mediastinum showing a right-

Positron emission tomography scan showing hypermetabolic right-sided pleural mesothelioma

History and exam

age between 60 and 85 years (common)

shortness of breath (common)

diminished breath sounds (common)

dullness to percussion (common)

Other diagnostic factors

chest pain (common)

constitutional symptoms (common)

abdominal distension and/or pain (uncommon)

simian virus 40 (SV-40)

Chest x-ray demonstrating total left-sided collapse and replacement of

Computed tomography scan of the lung showing a right-sided

Other tests to consider

chest MRI degree of tumour

PET scan further evaluates location

Positron emission tomography scan showing

basic metabolic panel usually normal

Condition Differentiating signs / Differentiating tests

Benign asbestos-related • Exposure to asbestos can • Pleural plaques are

enlarged regional lymph

Non-small cell lung • Typical features include • Chest CT scan shows

Condition Differentiating signs / Differentiating tests

Metastatic cancer • Symptoms will relate to • Chest CT scan shows

In patients with inoperable or recurrent mesothelioma, chemotherapy is often given in an attempt to

added to reduce the risk of haematological toxicity associated with pemetrexed.

There is no standard second-line chemotherapy in malignant pleural mesothelioma, although several

Inoperable or recurrent disease: palliative procedures

Treatment algorithm overview

plus pre- and/or postoperative chemotherapy

inoperable or recurrent disease

adjunct palliative procedures + supportive care

» Two distinct surgical approaches are

» EPP removes the parietal and visceral

» Pleurectomy with decortication is a more

» The superiority of EPP over pleurectomy with

days after the last dose

» In patients with potentially resectable

» Similarly, in patients who have undergone EPP,

» Vitamin supplementation, particularly B12

» See local specialist protocol for dosing

» The role of RT after extra-pleural

» Comprehensive RT after pleurectomy with

» In patients with inoperable or recurrent

» A randomised study compared chemotherapy

» Therefore, in appropriate patients with good

» Cisplatin is associated with nephrotoxicity,

» Bevacizumab may be added to cisplatin plus

» In patients for whom clinical trials are not an

» See local specialist protocol for dosing

» In addition to aiding diagnosis, thoracentesis

» Pleurodesis, defined as the artificial

thoracoscopic surgery (VATS) pleurodesis