Update on Treatment Options with a Focus
on Novel Therapies
Andrew R. Haas, MD, PhD, Daniel H. Sterman, MD*
Mesothelioma is an insidious mesothelial neo-
neum, or tunica vaginalis, with approximately 80%
of cases involving the thorax. The predominant
cause of malignant mesothelioma is exposure to
asbestos. The incidence of mesothelioma in the
United States is estimated to be approximately
2000 to 3000 cases per year, with an increasing
incidence worldwide, secondary to the prolifera-
tion and poor regulation of industrial and house-
hold use of asbestos.1–6
A nihilistic attitude regarding mesothelioma has
persisted among many physicians because of
significant associated morbidity and mortality, as
well as poor response to standard therapeutic
interventions. However, novel treatment para-
tumor responses, and prolonged survival.6–9This
article focuses on standard therapeutic interven-
tions for malignant pleural mesothelioma (MPM)
such as surgery, chemotherapy, and radiation
therapy, as well as experimental approaches
such as targeted therapy, immunotherapy, and
SURGERY FOR MPM
Surgery for MPM can be diagnostic, palliative, or
cytoreductive, although it is potentially associated
with significant morbidity and mortality. The
Section of Interventional Pulmonology and Thoracic Oncology, Pulmonary, Allergy, and Critical Care Division,
University of Pennsylvania Medical Center, 833 West Gates Building, 3400 Spruce Street, Philadelphia, PA
* Corresponding author.
E-mail address: email@example.com
?Malignant pleural mesothelioma?Radiation therapy?Chemotherapy?Multimodal therapy
? In the past decade, advances have been made that have improved the ability to treat malignant
? There is evidence that these treatments are increasing the quality and quantity of life for patients
? Multimodality treatment programs that combine maximal surgical cytoreduction with novel forms of
radiation therapy and more effective chemotherapy combinations may offer significant increases in
survival for certain subgroups of patients with mesothelioma.
? Lung-sparing surgery may allow improvements in pulmonary function after surgery-based multimo-
? Experimental treatments such as immunotherapy and gene therapy provide hope for all patients
with mesothelioma, and in the future may be combined with standard therapy in multimodality
Clin Chest Med 34 (2013) 99–111
0272-5231/13/$ – see front matter ? 2013 Elsevier Inc. All rights reserved.
development of thoracoscopy has allowed earlier
patients with MPM have advanced disease at
diagnosis, as well as comorbid medical illnesses,
Dyspnea from the accumulation of a pleural
effusion is the most common presenting symptom
of MPM. For symptomatic effusions in MPM, the
optimal palliative approach is maximal drainage
of the effusion and subsequent pleurodesis. The
most widely used compound for pleurodesis in
MPM is sterile talc, administered either as
a powder (poudrage) via thoracoscopy or as
a slurry via tube thoracostomy.10The presence
of bulky tumor in the pleural space, or entrapment
of the lung by a thick visceral pleural peel, is
a contraindication to pleurodesis in patients with
MPM. Attempts at talc pleurodesis in the setting
of lung entrapment can lead to a multiloculated
pleural space with a high risk of empyema. In
this setting of lung entrapment in MPM, the
preferred intervention is insertion of a tunneled in-
trapleural catheter to drain recurrent effusions and
provide effective palliation of dyspnea (Fig. 1).11
The primary concern regarding the use of tunneled
pleural catheters (TPCs) in mesothelioma is the
development of tumor implants at the insertion
site or along the subcutaneous tunnel.11,12Recent
reports of TPCs for malignant pleural effusions
(MPEs) show equivalent results for the control of
effusions compared with talc slurry pleurodesis.
management of symptomatic effusions in patients
with MPM, even in those whose lungs are unable
to expand.13Pleuroperiotoneal shunting, an alter-
native approach for dealing with lung entrapment
in pleural mesothelioma, carries the overt risk of
malignant seeding of the peritoneal cavity, and is
therefore infrequently used.
Thoracoscopic parietal pleurectomy is an alter-
native to talc pleurodesis in reducing the recur-
rence of pleural effusions in mesothelioma, and
with less morbidity than open pleurectomy.14
Complete parietal and visceral pleurectomy (pleur-
ectomy/decortication) may palliate dyspnea in
patients with mesothelioma with bulky intrapleural
disease with or without lung entrapment, but by it-
self has not been shown to prolong survival.15
Extrapleural pneumonectomy (EPP) is en bloc
resection of the lung, the parietal and visceral
pleurae, and portions of the ipsilateral pericardium
and diaphragm. It provides maximal tumor cytore-
duction and facilitates higher radiation dosage to
the involved hemithorax. EPP alone has no influ-
ence on survival in the absence of adjuvant
therapy. In most surgical series of EPP in MPM,
median survival is less than 2 years, with average
there are long-term survivors following EPP for
maximal cytoreduction as a component of multi-
modality treatment involving adjuvant radiation
therapy and postoperative chemotherapy.19–21
However, the benefits of EPP with adjuvant che-
motherapy with or without local radiotherapy are
limited to otherwise healthy patients with early-
stage disease, epithelial histology, and no medias-
tinal lymph node involvement. Patients with
biphasic or sarcomatoid histology and/or medias-
tinal or hilar node positivity have an ominous
Several approaches for adjuvant therapy in
conjunction with EPP have been studied. Investi-
Fig. 1. (A) Tunneled pleural catheters (TPCs) are an important method of palliation in patients with mesothe-
lioma and recurrent symptomatic pleural effusions. (B) Thoracoscopic placement of TPCs can be performed
even in the setting of prior talc pleurodesis to facilitate intrapleural instillation of experimental therapies. (Cour-
tesy of Dr Joseph Friedberg, Division of Thoracic Surgery, Perelman School of Medicine of the University of Penn-
sylvania, Philadelphia, PA.)
Haas & Sterman
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Malignant Pleural Mesothelioma