-
Current Oncology Reports Nov 2022For patients with malignant pleural mesothelioma, prognosis is poor with extremely low 5-year survival rates and limited therapeutic options. Here, we review the current... (Review)
Review
PURPOSE OF REVIEW
For patients with malignant pleural mesothelioma, prognosis is poor with extremely low 5-year survival rates and limited therapeutic options. Here, we review the current treatment landscape for mesothelioma and highlight promising future therapeutic directions.
RECENT FINDINGS
Evolving frontline therapeutic options for mesothelioma include VEGF inhibition in combination with chemotherapy and dual immune checkpoint inhibition, with synergisms between the therapies and response prediction via biomarkers also being explored. Evolving experimental treatments for mesothelioma include PARP and ALK inhibitors, dendritic and CAR T-cell therapies, anti-mesothelin vaccines, and oncolytic viral therapies, representing timely advances in the field. The therapeutic landscape for malignant pleural mesothelioma is evolving and preferred treatment in the frontline and later settings will likely evolve with it. However, this does not preclude the evidence for including multi-modal therapies spanning angiogenesis and immune checkpoint inhibitors, and biomarker utilization, in current clinical trials and management.
Topics: Humans; Mesothelioma, Malignant; Pleural Neoplasms; Immune Checkpoint Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Vascular Endothelial Growth Factor A; Lung Neoplasms; Immunotherapy; Mesothelioma; Receptor Protein-Tyrosine Kinases
PubMed: 35657483
DOI: 10.1007/s11912-022-01302-3 -
Journal of Cardiothoracic Surgery Feb 2023Solitary fibrous tumors (SFTs) are rare mesenchymal pleural neoplasms with an overall good prognosis and low recurrence rate if completely resected and if degree of... (Review)
Review
Solitary fibrous tumors (SFTs) are rare mesenchymal pleural neoplasms with an overall good prognosis and low recurrence rate if completely resected and if degree of differentiation is favorable. Within the last decade, advances in research have led to more reliable methods of differentiating SFTs from other soft tissue tumors. Historically, several markers were used to distinguish SFTs from similar tumors, but these markers had poor specificity. Recent evidence showed NAB2-STAT6 fusion gene to be a distinct feature of SFTs with 100% specificity and sensitivity. Surgical resection, with an emphasis on obtaining negative margins, is the mainstay of treatment for SFTs. Preoperative planning with detailed imaging is imperative to delineate the extent of disease and vascular supply. One important radiologic distinction to aid delineation of a pleural-based tumor compared to a pulmonary parenchymal-based tumor is the angle that the tumor forms with the chest wall, which is obtuse for a pleural-based tumor, and acute for tumors of the lung parenchyma. Often, preoperative tissue diagnosis is not available, and surgery is both diagnostic and curative. Intraoperatively, emphasis should be on complete resection with negative margins. SFTs are resected via several approaches: thoracotomy, sternotomy with the option of hemi-clamshell extension, video-assisted thoracoscopic surgery, and robotic approach, which is increasingly being used and is our preference. We recommend a minimally invasive approach for most lesions, and have resected SFTs of the pleura that are up to 12 cm with the robotic approach. However, the current literature often cites 5 cm as the cut off for an open thoracotomy. Nevertheless, even with larger tumors, a minimally invasive robotic approach is our preference and practice. For giant SFTs (> 20 cm), an open approach may be preferable. Multiple thoracotomies and rib resection may be required to gain adequate exposure and ensure complete resection in these tumors. However, it is noteworthy that most of these tumors have a soft consistency and thus, once bagged, can easily be removed minimally invasively, and thus minimally invasive approach should not be completely ruled out. Recurrence in SFTs usually results from incomplete resection and redo surgery may portend a favorable prognosis.
Topics: Humans; Pleura; Severe Fever with Thrombocytopenia Syndrome; Solitary Fibrous Tumors; Pleural Neoplasms; Prognosis
PubMed: 36823638
DOI: 10.1186/s13019-023-02168-7 -
Thoracic Cancer Dec 2020Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy,...
BACKGROUND
Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM.
METHODS
We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields.
RESULTS
A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months.
CONCLUSIONS
Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Mesothelioma, Malignant; Middle Aged; Pleural Neoplasms; Prospective Studies; Radiotherapy, Intensity-Modulated
PubMed: 33030313
DOI: 10.1111/1759-7714.13668 -
Targeted Oncology Jul 2022Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a... (Review)
Review
Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12-18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma's carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway's member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Asbestos; Bevacizumab; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pemetrexed; Pleural Neoplasms
PubMed: 35906513
DOI: 10.1007/s11523-022-00900-2 -
Medicina (Kaunas, Lithuania) Dec 2022Malignant pleural mesothelioma (MPM) is an aggressive and rare malignant pleural tumor. MPM patients diagnosed in Beijing Chaoyang Hospital and Beijing Tongren...
Malignant pleural mesothelioma (MPM) is an aggressive and rare malignant pleural tumor. MPM patients diagnosed in Beijing Chaoyang Hospital and Beijing Tongren Hospital were the focus of this study. We collected and analyzed the histological, radiological, and metabolic features of MPM patients. At the same time, Cox univariable and multivariable analyses were used to explore the laboratory risk factors affecting the prognosis of MPM patients. A total of 129 MPM patients were included in this study. MPM includes three main histological subtypes: epithelioid, sarcomatoid and biphasic. Among them, epithelial subtypes accounted for the highest proportion. Calretinin, Wilms' tumor gene (WT1), cytokeratin 5/6 (CK5/6), and D2-40 were the most useful mesothelial markers to support a MPM diagnosis. The imaging features of MPM patients are pleural thickening and pleural effusion. In PET-CT, the affected pleura showed obvious high uptake of tracer, and the degree was related to the specific subtype. The median follow-up time was 55.0 (30.0, 94.0) months. A total of 92 (71.3%) patients died during follow-up. The median survival time of patients was 21.0 (9.0, 48.0) months. The Cox multivariable analysis showed that age [hazard ratio (HR), 1.824; 95% confidence interval (CI) 1.159-2.872; = 0.009; uncorrected], ESR (HR, 2.197; 95% CI 1.318-3.664; = 0.003; with Bonferroni correction), lymphocytes (HR, 0.436; 95% CI 0.258-0.737; = 0.002; with Bonferroni correction), platelets (HR, 1.802; 95% CI 1.084-2.997; = 0.023; uncorrected) and total protein (HR, 0.625; 95% CI 0.394-0.990; = 0.045; uncorrected) were independent risk factors for prognosis, after adjusting for confounding factors. Age, ESR, lymphocytes, platelets and total protein may be related to the prognosis of MPM patients. Summarizing the histological, radiological, and metabolic features of MPM patients in the two centers can increase clinicians' understanding of this rare tumor.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Positron Emission Tomography Computed Tomography; Prognosis; Pleural Neoplasms; Lung Neoplasms
PubMed: 36557076
DOI: 10.3390/medicina58121874 -
Thorax Nov 2021Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is... (Review)
Review
Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations, spheroids and microfluidic chips have more recently been used to investigate the role of the three-dimensional environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice and patient-derived xenografts. Here, we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.
Topics: Animals; Asbestos; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mice; Pleural Neoplasms
PubMed: 33692175
DOI: 10.1136/thoraxjnl-2020-216602 -
Thoracic Cancer Jan 2023Malignant pleural mesothelioma (MPM) is an invasive, aggressive pleural tumor with a predominantly local spread. The objective of this study was to assess thoracic...
BACKGROUND
Malignant pleural mesothelioma (MPM) is an invasive, aggressive pleural tumor with a predominantly local spread. The objective of this study was to assess thoracic ultrasound (TUS) as an imaging modality with high sensitivity for the identification of malignant pleural involvement and in order to guide pleural biopsies.
METHODS
In this retrospective single-center study between January 2018 and June 2022, 51 consecutive patients with impassable circumferential pleural thickening underwent TUS at the Thoracic Surgery Unit of the Vanvitelli University of Naples. Pleural biopsies were performed, and then large and multiple samples were sent to the pathological anatomy for histological examination.
RESULTS
In all patients who underwent ultrasound examination, we chose the optimal point of entry to perform pleural biopsies and selected the areas of greater thickening without pleural effusion. No patient had any complications. No drainage tubes were placed after the pleural biopsies and no pneumothorax was present during the following days of hospitalization. The patients were discharged on the second postoperative day.
CONCLUSION
With TUS the precise pleural thickening localization, local infiltration, mass extent, its nature (solid, cystic or complex) and ultrasound features can be easily defined. Furthermore, ultrasound is more economical than computed tomography and avoids the risks associated with radiation. Thoracic ultrasound is an important component of the diagnostic procedure in detecting a safe entry site for biopsies of MPMs.
Topics: Humans; Retrospective Studies; Pleura; Pleural Diseases; Pleural Neoplasms; Mesothelioma, Malignant
PubMed: 36415167
DOI: 10.1111/1759-7714.14735 -
International Journal of Molecular... Sep 2020Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.
Topics: Animals; Biomarkers, Tumor; Genomics; Humans; Mesothelioma, Malignant; Phenomics; Pleural Neoplasms
PubMed: 32882916
DOI: 10.3390/ijms21176342 -
Genome Medicine May 2022Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM...
BACKGROUND
Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.
METHODS
We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study. This was combined with RNA-seq analysis to characterize the tumour immune environment.
RESULTS
The comprehensive genome analysis identified 12 driver genes, including new candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed SBS5/40 were dominant in 93% of samples, and defects in homologous recombination repair were infrequent in our cohort. The tumour immune environment contained high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immune suppressive environment. The expression of TGFB1 was associated with overall survival. A small subset of samples (less than 10%) had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a 'hot' immune environment independent of the somatic mutations.
CONCLUSIONS
We propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future.
Topics: Genomics; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Tumor Microenvironment
PubMed: 35637530
DOI: 10.1186/s13073-022-01060-8 -
British Journal of Cancer Jan 2020Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.
Topics: Animals; Antineoplastic Agents; Asbestos; Cell Transformation, Neoplastic; Cisplatin; Humans; Loss of Function Mutation; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Oxidation-Reduction; Pleural Neoplasms; Reactive Oxygen Species; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 31819191
DOI: 10.1038/s41416-019-0661-9