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Multimodality treatment of malignant pleural mesothelioma.

ABSTRACT: Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.

SUBMITTER: Berzenji L

PROVIDER: S-EPMC6198256 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Multimodality treatment of malignant pleural mesothelioma.

Berzenji Lawek L Van Schil Paul P

F1000Research 20181022

Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which t ...[more]

PMID: 30410726

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Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Boston's Brigham and Women's Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patients' resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH.

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Multimodality treatment of malignant pleural mesothelioma.

Publications

Multimodality treatment of malignant pleural mesothelioma.

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