Malignant Mesothelioma: Has Anything Changed?

2019 ◽  
Vol 40 (03) ◽  
pp. 347-360 ◽  
Author(s):  
Roger Y. Kim ◽  
Daniel H. Sterman ◽  
Andrew R. Haas
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Multimodal Therapy ◽  
Asbestos Exposure ◽  
Treatment Options ◽  
Standard Of Care ◽  
Turn Of The Century ◽  
Clinical Approach ◽  
Pleural Mesothelioma ◽  
Dismal Prognosis ◽  
Near Future

AbstractMalignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.

scholarly journals SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020)

2021 ◽  
Vol 23 (5) ◽  
pp. 980-987 ◽  
Author(s):  
E. Nadal ◽  
J. Bosch-Barrera ◽  
S. Cedrés ◽  
J. Coves ◽  
R. García-Campelo ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Early Stage ◽  
Asbestos Exposure ◽  
Standard Of Care ◽  
Tumor Board ◽  
Pleural Mesothelioma ◽  
Therapeutic Approaches ◽  
Dismal Prognosis ◽  
Line Chemotherapy ◽  
Multidisciplinary Tumor Board

AbstractMesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.

scholarly journals Biomarker-guided targeted and immunotherapies in malignant pleural mesothelioma

2020 ◽  
Vol 12 ◽  
pp. 175883592097142
Author(s):  
Haitang Yang ◽  
Duo Xu ◽  
Ralph A. Schmid ◽  
Ren-Wang Peng
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Tumor Suppressor Genes ◽  
Treatment Options ◽  
Standard Of Care ◽  
Genetic Alterations ◽  
Homozygous Deletion ◽  
Pleural Mesothelioma ◽  
Precision Oncology ◽  
Tremendous Progress ◽  
High Degree

Malignant pleural mesothelioma (MPM) is a lethal thoracic malignancy whose incidence is still increasing worldwide. MPM is characterized by frequent inactivation of tumor-suppressor genes (TSGs), e.g., the homozygous deletion of CDKN2A/2B and various genetic alterations that inactivate BAP1, NF2, LATS1/2, and TP53. The leading cause for the poor prognosis of patients with MPM is the lack of effective treatment options, with conventional chemotherapy being the standard of care in the clinic, which has remained unchanged for almost 20 years. Precision oncology, a burgeoning effort to provide precise cancer treatment tailored to unique molecular changes in individual patients, has made tremendous progress in the last decade in several cancers, but not in MPM. Recent studies indicate a high degree of tumor heterogeneity in MPM and the importance to optimize histological and molecular classifications for improved treatment. In this review, we provide an up-to-date overview of recent advances in MPM by focusing on new stratifications of tumor subgroups, specific vulnerabilities associated with functional loss of TSGs and other biomarkers, and potential clinical implications. The molecularly based subdivisions not only deepen our understanding of MPM pathobiology, but more importantly, they may raise unprecedented new hopes for personalized treatment of MPM patients with biomarker-guided targeted and immunotherapies.

scholarly journals Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment

2016 ◽  
Vol 25 (142) ◽  
pp. 472-486 ◽  
Author(s):  
Anna C. Bibby ◽  
Selina Tsim ◽  
Nikolaos Kanellakis ◽  
Hannah Ball ◽  
Denis C. Talbot ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Imaging Techniques ◽  
Asbestos Exposure ◽  
Treatment Options ◽  
Incidence Rates ◽  
Pleural Mesothelioma ◽  
Global Epidemic ◽  
Pleural Surface ◽  
New Treatment ◽  
Trimodality Treatment

Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised.

New Era for Malignant Pleural Mesothelioma: Updates on Therapeutic Options

2022 ◽  
Author(s):  
Anne S. Tsao ◽  
Harvey I. Pass ◽  
Andreas Rimner ◽  
Aaron S. Mansfield
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Checkpoint Inhibitors ◽  
Treatment Plan ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Pleural Mesothelioma ◽  
Frontline Treatment ◽  
Rare Malignancy

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease.

scholarly journals Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3932
Author(s):  
Dannel Yeo ◽  
Laura Castelletti ◽  
Nico van Zandwijk ◽  
John E. J. Rasko
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Treatment Options ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Pleural Mesothelioma ◽  
Normal Tissues ◽  
Drug Conjugates ◽  
Aggressive Cancer ◽  
Immunotherapy Target ◽  
Bull's Eye

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM. Many other solid cancers overexpress MSLN, and this is associated with worse survival rates. However, this association has not been found in MPM, and the exact biological role of MSLN in MPM requires further exploration. Here, we discuss the current research on the diagnostic and prognostic value of MSLN in MPM patients. Furthermore, MSLN has become an attractive immunotherapy target in MPM, where better treatment strategies are urgently needed. Several MSLN-targeted monoclonal antibodies, antibody–drug conjugates, immunotoxins, cancer vaccines, and cellular therapies have been tested in the clinical setting. The biological rationale underpinning MSLN-targeted immunotherapies and their potential to improve MPM patient outcomes are reviewed.

scholarly journals Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1138
Author(s):  
Martina Schiavello ◽  
Elena Gazzano ◽  
Loredana Bergandi ◽  
Francesca Silvagno ◽  
Roberta Libener ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Malignant Pleural Mesothelioma ◽  
Antioxidant Defense ◽  
Asbestos Exposure ◽  
Predictive Biomarkers ◽  
Antioxidant Systems ◽  
Pleural Mesothelioma ◽  
Related Factor ◽  
Aggressive Cancer

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.

scholarly journals Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Cheng-Kuan Lin ◽  
Yu-Ying Chang ◽  
Jung-Der Wang ◽  
Lukas Jyuhn-Hsiarn Lee
Keyword(s):  
Cohort Study ◽  
General Population ◽  
Incidence Rate ◽  
Malignant Pleural Mesothelioma ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Asbestos Exposure ◽  
Pleural Mesothelioma ◽  
Calendar Period ◽  
Incident Cases

Objective. This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.Methods. All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.Results. The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25–8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19–16.89) for the workers employed for more than 20 years in asbestos-related factories.Conclusions. This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.

Case 13.8

2014 ◽  
pp. 628-629
Author(s):  
Christine U. Lee ◽  
James F. Glockner
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
The United States ◽  
Extrapleural Pneumonectomy ◽  
Parietal Pleura ◽  
Pleural Mesothelioma ◽  
Pleural Plaques ◽  
Abnormal Chest ◽  
Left Pleura ◽  
Histologic Subtypes

62-year-old man with shortness of breath and an abnormal chest CT Axial 3D SPGR postgadolinium images (Figure 13.8.1) demonstrate diffuse thickening and enhancement of the left pleura, with a few minimally enhancing, focal right-sided pleural plaques. Malignant pleural mesothelioma Malignant pleural mesothelioma is a rare neoplasm that originates from the mesothelial cells lining the visceral and parietal pleura. The incidence of malignant pleural mesothelioma in the United States is 15 cases per million; there is a strong correlation with asbestos exposure. Malignant pleural mesothelioma is divided into 3 histologic subtypes: epithelial (55%-65%), sarcomatoid (10%-15%), and mixed (20%-35%). Patients with epithelial malignant pleural mesothelioma have the best prognosis, and among those with limited disease who undergo extrapleural pneumonectomy (removal of the pleura, lung, hemidiaphragm, and part of the pericardium), survival is longer (5-year survival, 39%) than among all patients (median survival, 8-18 months after diagnosis)....

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