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The Oncologist Jul 2007The incidence of malignant pleural mesothelioma (MPM) is increasing worldwide, and is predicted to peak in the next 10-20 years. Difficulties in MPM diagnosis and... (Review)
Review
The incidence of malignant pleural mesothelioma (MPM) is increasing worldwide, and is predicted to peak in the next 10-20 years. Difficulties in MPM diagnosis and staging, especially of early disease, have thwarted the development of a universally accepted therapeutic approach. Single modality therapies (surgery, radiotherapy, chemotherapy) have generally failed to significantly prolong patient survival. As a result, multimodality treatment regimens have been developed. Radical surgery with extrapleural pneumonectomy and adjuvant treatments has become the preferred option in early disease, but the benefits of such an aggressive approach have been questioned because of significant treatment-related morbidity and mortality. In the past few years, there have been several major advances in the management of patients with MPM, including more accurate staging and patient selection, improvements in surgical techniques and postoperative care, novel chemotherapy regimens with definite activity such as antifolate (pemetrexed or raltitrexed)-platinum combinations, and new radiotherapy techniques such as intensity-modulated radiation therapy. Induction chemotherapy followed by surgery and adjuvant radiotherapy has shown promising results. A number of molecular alterations occurring in MPM have been reported, providing broader insights into its biology and leading to the identification of new targets for therapy. However, currently available treatments still appear to have modest results. Further studies are needed to provide evidence-based recommendations for the treatment of early and advanced stages of this disease.
Topics: Combined Modality Therapy; Humans; Mesothelioma; Neoplasm Staging; Pleural Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 17673616
DOI: 10.1634/theoncologist.12-7-850 -
Journal of Thoracic Oncology : Official... Mar 2023Malignant pleural mesothelioma (MPM) is an aggressive primary malignancy of the pleura that presents unique radiologic challenges with regard to accurate and... (Review)
Review
Malignant pleural mesothelioma (MPM) is an aggressive primary malignancy of the pleura that presents unique radiologic challenges with regard to accurate and reproducible assessment of disease extent at staging and follow-up imaging. By optimizing and harmonizing technical approaches to imaging MPM, the best quality imaging can be achieved for individual patient care, clinical trials, and imaging research. This consensus statement represents agreement on harmonized, standard practices for routine multimodality imaging of MPM, including radiography, computed tomography, F-2-deoxy-D-glucose positron emission tomography, and magnetic resonance imaging, by an international panel of experts in the field of pleural imaging assembled by the International Mesothelioma Interest Group. In addition, modality-specific technical considerations and future directions are discussed. A bulleted summary of all technical recommendations is provided.
Topics: Humans; Mesothelioma, Malignant; Public Opinion; Pleural Neoplasms; Lung Neoplasms; Neoplasm Staging; Mesothelioma; Positron-Emission Tomography
PubMed: 36549385
DOI: 10.1016/j.jtho.2022.11.018 -
Cancer Control : Journal of the Moffitt... Oct 2006The solitary fibrous tumor of the pleura (SFTP) is a rare primary tumor arising from mesenchymal cells in the areolar tissue subjacent to the mesothelial-lined pleura.... (Review)
Review
BACKGROUND
The solitary fibrous tumor of the pleura (SFTP) is a rare primary tumor arising from mesenchymal cells in the areolar tissue subjacent to the mesothelial-lined pleura. Only about 800 cases have been reported in the medical literature. The tumor appears to be unrelated to malignant pleural mesothelioma, the most common primary tumor of the pleura.
METHODS
In just over half of these cases, the neoplasm presents as an asymptomatic mass, is often quite large, and is benign in 78% to 88% of patients. The initial evaluation and diagnosis, tumor classification, surgical treatment, results of therapy, and long-term prognosis are reviewed, based on a selective review of the literature from MEDLINE beginning 1980.
RESULTS
Complete en bloc surgical resection is the preferred treatment of benign and malignant varieties of the tumor. The pedunculated tumors attached to the visceral pleura can be effectively treated with a wedge resection of lung. Sessile tumors arising on the lung require a larger lung resection. Sessile tumors on the chest wall require wide local excision, often with chest wall resection because of their propensity for local recurrence. Adjuvant therapy remains controversial in SFTP.
CONCLUSIONS
Benign SFTP has a high cure rate and an 8% local recurrence rate that is usually amenable to curative re-excision. Malignant SFTP, especially the more common sessile type, has a 63% recurrence rate even with complete resection. The majority of patients with recurrent disease die of the tumor within 2 years. Nevertheless, the overall long-term cure rate for all patients is 88% to 92%.
Topics: Diagnosis, Differential; Humans; Incidence; Neoadjuvant Therapy; Neoplasms, Fibrous Tissue; Pleural Neoplasms; Thoracic Surgical Procedures; Tomography, X-Ray Computed; United States
PubMed: 17075563
DOI: 10.1177/107327480601300403 -
Cancer Medicine Jun 2023The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not...
OBJECTIVES
The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not been fully verified. We aimed to develop an individualized prediction model for identifying optimal candidates for PORT among MPM patients who received surgery plus chemotherapy and externally validate the performance of the new TNM staging scheme.
MATERIALS AND METHODS
Detailed characteristics of MPM patients during 2004-2015 were retrieved from SEER registries. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics (age, sex, histologic type, stage, and type of surgery) between the PORT group and no-PORT group. A novel nomogram was constructed based on independent prognosticators identified by multivariate Cox regression model. The discriminatory performance and degree of calibration were evaluated. We stratified patients into different risk groups according to nomogram total scores and estimated the survival benefit of PORT in different subgroups in order to identify the optimal candidates.
RESULTS
We identified 596 MPM patients, among which 190 patients (31.9%) received PORT. PORT conferred significant survival benefit in the unmatched population, while there was no significant survival difference favoring PORT in the matched population. The C-index of the new TNM staging scheme was closed to 0.5, which represented a poor discriminatory ability. A novel nomogram was constructed based on clinicopathological factors, including age, sex, histology, and N stage. We stratified patients into three risk groups. Subgroup analyses indicated that PORT was beneficial for high-risk group (p = 0.003) rather than low-risk group (p = 0.965) and intermediate-risk group (p = 0.661).
CONCLUSION
We established a novel predictive model, which could make individualized prediction of survival benefit of PORT for MPM and could compensate for weakness in TNM staging system.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Lung Neoplasms; Neoplasm Staging; Prognosis
PubMed: 37076977
DOI: 10.1002/cam4.5955 -
International Journal of Molecular... Nov 2021Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach.... (Review)
Review
Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.
Topics: Biomarkers, Tumor; Epithelial-Mesenchymal Transition; Humans; Mesothelioma, Malignant; MicroRNAs; Neoplasm Metastasis; Neoplasm Proteins; Pleural Neoplasms; RNA, Neoplasm; Transforming Growth Factor beta
PubMed: 34830097
DOI: 10.3390/ijms222212216 -
Pathology, Research and Practice Dec 2021The role of 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) in evaluating induction chemotherapy in pleural mesothelioma...
The role of 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) in evaluating induction chemotherapy in pleural mesothelioma (PM) patients is debated. We compared histology at tumor sites with high versus low [F]FDG uptake in order to define a morphologic correlate for persistent metabolic activity. Twenty PM patients with talc pleurodesis and induction chemotherapy followed by extrapleural pleuro-pneumonectomy (EPP, n = 17) or tumor debulking (n = 3) were included. All patients received a PET/CT scan prior to surgery. Orthogonal tissue sections of pleural rind (n total=86) were taken at areas of maximum standardized uptake value (SUV, n = 53) and of low [F]FDG uptake (n = 33) and scored on hematoxylin-eosin and immunohistochemical stainings. Total metabolic activity was scored semiquantitatively. Mean SUV of hot and cold spots correlated with total metabolic activity per patient, but no correlation was found with ypT and tumor cells were present in both hot and cold areas. SUV of only hot spots and cold versus hot spots as well as cold versus hot patients correlated with increased thickness of total pleural rind and fibrosis reaction, but not thickness of vital tumor cells or giant cell reaction. They further correlated with increased expression of glucose transporter 1 (GLUT1) in giant cells but not mesothelioma amount, density, vitality or vascularization. Biphasic histology was associated with SUV in only hot spots and higher total metabolic activity (all p-values <0.05). Interpretation of [F]FDG PET/CT in PM patients is difficult after talc pleurodesis and induction chemotherapy. High glucose turnover is mostly related to fibro-inflammatory remodeling of the pleural rind and GLUT1 transporter expression in giant cells. Response assessment using this technology should only be done to assess extra-thoracic lesions.
Topics: Female; Fluorodeoxyglucose F18; Humans; Induction Chemotherapy; Male; Mesothelioma; Neoadjuvant Therapy; Neoplasm Staging; Pleura; Pleural Neoplasms; Pleurodesis; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Talc; Treatment Outcome
PubMed: 34749212
DOI: 10.1016/j.prp.2021.153660 -
Thoracic Surgery Clinics Nov 2020In the absence of standardized treatment algorithms for patients with malignant pleural mesothelioma, one of the main difficulties remains patient allocation to... (Review)
Review
In the absence of standardized treatment algorithms for patients with malignant pleural mesothelioma, one of the main difficulties remains patient allocation to therapies with potential benefit. This article discusses clinical, radiologic, pathologic, and molecular prognostic factors as well as genetic background leading to preoperative identification of benefit from surgery, which have been investigated over the past years to simplify and at the same time specify patient selection for surgical treatment.
Topics: Humans; Mesothelioma, Malignant; Patient Selection; Pleural Neoplasms; Preoperative Care; Prognosis
PubMed: 33012431
DOI: 10.1016/j.thorsurg.2020.08.003 -
Respirology (Carlton, Vic.) Jan 2017Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth...
BACKGROUND AND OBJECTIVE
Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo-resistance of mesothelioma.
METHODS
Pleural fluid samples from 151 patients (56 mesothelioma, 60 metastatic pleural cancer and 35 benign) were used. Seven validated human mesothelioma cell lines and three primary cultured mesothelioma lines were employed.
RESULTS
Pleural fluid from mesothelioma patients (diluted to 30%) consistently stimulated cell proliferation (trypan-blue cell viability assay) in five mesothelioma cell lines tested by (median) 2.23-fold over controls (all P < 0.0001). The fluid also induced cell migration by (median) 2.13-fold in six mesothelioma cell lines using scratch-wound assay. In a murine flank model of mesothelioma, tumour infused with daily instillations of pleural fluid grew significantly faster over saline controls (median 52.5 cm vs 28.0 cm at day 13, P = 0.028). Addition of MPE (diluted to 30%) to culture media significantly protected mesothelioma from cisplatin/pemetrexed-induced cell death in all three cell lines tested (median fold reduction of 1.29, 1.98 and 3.90, all P < 0.001 vs control). The growth effects of matched pleural fluid and cultured mesothelioma cells from the same patients did not differ significantly from unmatched pairs.
CONCLUSION
This 'proof-of-concept' study reveals potent biological capabilities of malignant pleural fluid in mesothelioma pathobiology.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Cisplatin; Drug Resistance, Neoplasm; Exudates and Transudates; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mice; Pemetrexed; Pleural Effusion, Malignant; Pleural Neoplasms
PubMed: 27560254
DOI: 10.1111/resp.12874 -
In Vivo (Athens, Greece) 2018A strategy for improving survival of malignant pleural mesothelioma (MPM) patients is earlier diagnosis paired with earlier stage implementation of therapeutic...
BACKGROUND/AIM
A strategy for improving survival of malignant pleural mesothelioma (MPM) patients is earlier diagnosis paired with earlier stage implementation of therapeutic interventions. This study aimed to determine the clinical signs of early-stage MPM to aid an earlier diagnosis and earlier-stage intervention.
MATERIALS AND METHODS
Out of the 72 cases in our institution, 40 cases with F-FDG-PET/CT-negative MPM were retrospectively identified between 2007 and 2015. Overall survival rates were determined and compared with pathological features, histology, and treatment.
RESULTS
The biphasic histological type of early-stage MPM was characterized by poor prognosis (p=0.0006). Additionally, the cytology-negative group (Class III and below) showed significantly shorter survival times (p=0.0290). There was no significant difference in survival between patients who received pleurectomy and those who received chemotherapy only (p=0.6991). Bimodal therapy resulted in a longer survival rate than trimodal therapy.
CONCLUSION
In early-stage PET-negative MPM cases, biphasic histology and pleural effusion of Class III and below correlated with a poor prognosis. Surgical treatment using pleurectomy/decortication resulted in higher patient survival outcomes than therapy with extrapleural pneumonectomy.
Topics: Aged; Combined Modality Therapy; Female; Fluorodeoxyglucose F18; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Neoplasm Staging; Pleural Neoplasms; Positron Emission Tomography Computed Tomography; Treatment Outcome
PubMed: 30150440
DOI: 10.21873/invivo.11360 -
Cancer Reports (Hoboken, N.J.) Apr 2024Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral...
BACKGROUND
Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural-based sarcoma of predominantly pediatric patients suggest EPP may be a life-prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center.
METHODS
Clinicopathologic variables, surgical details, and follow-up information were extracted for patients undergoing EPP for pleural-based sarcoma between August 2017 and December 2020. Primary outcomes were event-free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease-free interval (DFI) prior to EPP, and early and late postoperative complications.
RESULTS
Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural-based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow-up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation-related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low-grade histology and achieving a metabolic response to preoperative chemotherapy.
CONCLUSIONS
In adults with pleural-based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.
Topics: Adult; Humans; Child; Pneumonectomy; Pleural Neoplasms; Neoplasm Recurrence, Local; Mesothelioma; Sarcoma
PubMed: 38627902
DOI: 10.1002/cnr2.2065