Perspectives on the Treatment of Malignant Pleural Mesothelioma

Janes, Sam M.; Alrifai, Doraid; Fennell, Dean A.

doi:10.1056/nejmra1912719

Cited by 95 publications

(97 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Example images of immune cell phenotypes associated with survival are presented in Figure 1. Regarding checkpoint inhibitors (PD-1 and PD-L1) and exhaustion markers (TIM3, LAG3, and IDO), which are targets of immunotherapies and thus are also currently of great interest also in mesothelioma research (26), we did not observe any associations with patient survival (Supplementary Table S4) (6, 7).…”

Section: Univariate Cox Regression Analysis Of Immune Cell Populationsmentioning

confidence: 76%

Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma

et al. 2022

View full text Add to dashboard Cite

BackgroundPleural mesothelioma (MPM) is an aggressive malignancy with an average patient survival of only 10 months. Interestingly, about 5%–10% of the patients survive remarkably longer. Prior studies have suggested that the tumor immune microenvironment (TIME) has potential prognostic value in MPM. We hypothesized that high-resolution single-cell spatial profiling of the TIME would make it possible to identify subpopulations of patients with long survival and identify immunophenotypes for the development of novel treatment strategies.MethodsWe used multiplexed fluorescence immunohistochemistry (mfIHC) and cell-based image analysis to define spatial TIME immunophenotypes in 69 patients with epithelioid MPM (20 patients surviving ≥ 36 months). Five mfIHC panels (altogether 21 antibodies) were used to classify tumor-associated stromal cells and different immune cell populations. Prognostic associations were evaluated using univariate and multivariable Cox regression, as well as combination risk models with area under receiver operating characteristic curve (AUROC) analyses.ResultsWe observed that type M2 pro-tumorigenic macrophages (CD163+pSTAT1−HLA-DRA1−) were independently associated with shorter survival, whereas granzyme B+ cells and CD11c+ cells were independently associated with longer survival. CD11c+ cells were the only immunophenotype increasing the AUROC (from 0.67 to 0.84) when added to clinical factors (age, gender, clinical stage, and grade).ConclusionHigh-resolution, deep profiling of TIME in MPM defined subgroups associated with both poor (M2 macrophages) and favorable (granzyme B/CD11c positivity) patient survival. CD11c positivity stood out as the most potential prognostic cell subtype adding prediction power to the clinical factors. These findings help to understand the critical determinants of TIME for risk and therapeutic stratification purposes in MPM.

show abstract

Section: Univariate Cox Regression Analysis Of Immune Cell Populationsmentioning

confidence: 76%

Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Malignant pleural mesothelioma (MPM) is an aggressive, incurable thoracic cancer that is strongly associated with asbestos exposure. Despite recent advances in treatment, the fiveyear survival rate remains only 5 to 10% [1]. It is believed that screening and early detection could reduce mortality, which prompted an ongoing search for MPM biomarkers more than 30 years ago [2,3].…”

Section: Introductionmentioning

confidence: 99%

External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma

Janssens

Schillebeeckx

Zwijsen

et al. 2022

Cancers

View full text Add to dashboard Cite

During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, we performed the first external validation of a VOC-based prediction model for MPM. The external validation cohort was prospectively recruited, consisting of 47 MPM patients and 76 asbestos-exposed (AEx) controls. The predictive performance of the previously developed model was assessed by determining the degree of agreement between the predicted and actual outcome of the participants (patient/control). Additionally, to optimise the performance, the model was updated by refitting it to the validation cohort. External validation revealed a poor performance of the original model as the accuracy was estimated at only 41%, indicating poor generalisability. However, subsequent updating of the model improved the differentiation between MPM patients and AEx controls significantly (73% accuracy, 92% sensitivity, and 92% negative predictive value), substantiating the validity of the original predictors. This updated model will be more generalisable to the target population and exhibits key characteristics of a potential screening test for MPM, which could significantly impact MPM management.

show abstract

“…Even though the mining and industrial use of asbestos has been banned or strictly regulated in many countries, including those in the European Union, Russia, Kazakhstan and China contribute to more than 80% of the global production. Global consumption remains high particularly in swing states, where the import and usage of asbestos without adequate safety equipment will inevitably lead to a rise in global disease burden in the coming decades [ 2 , 3 , 4 ]. Well-conducted clinical trials, investment in research, and development of new and more effective drugs that are affordable globally are the current requirements to improve the treatment landscape in mesothelioma.…”

Section: Introductionmentioning

confidence: 99%

Current Management and Future Perspective in Pleural Mesothelioma

Shah

Klotz

Glade

2022

Cancers

View full text Add to dashboard Cite

Pleural mesothelioma is an aggressive malignancy arising from pleural mesothelial cell lining, predominantly associated with prior exposure to asbestos. The ban on asbestos use has led to its lower incidence in many countries, but globally the disease burden is expected to rise. Therefore, well-planned research is needed to develop more effective, tolerable and affordable drugs. The development of novel treatment has been too slow, with only two regimens of systemic therapy with robust phase 3 data approved formally to date. The treatment scenario for resectable disease remains controversial. However, recent developments in the understanding of disease and clinical trials have been encouraging, and may add better treatment options in the coming years. In this review, we discuss the current treatment options for pleural mesothelioma and shed light on some recent studies and ongoing trials.

show abstract

Perspectives on the Treatment of Malignant Pleural Mesothelioma

Cited by 95 publications

References 75 publications

Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma

Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma

External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma

Current Management and Future Perspective in Pleural Mesothelioma

Contact Info

Product

Resources

About