bims-mesote Biomed News
on Mesothelioma
Issue of 2021–09–19
six papers selected by
Laura Mannarino, Humanitas Research
  1. Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy.
  2. GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma.
  3. Treatment Patterns and Outcomes of Patients With Advanced Pleural Mesothelioma at an Academic Referral Centre.
  4. Evidence for marked underutilization of insurance billing in malignant pleural mesothelioma in Finland.
  5. Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma.
  6. Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.
  1. J Immunother Cancer. 2021 Sep;pii: e003032. [Epub ahead of print]9(9):
    Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy.
    James Harber, Tamihiro Kamata, Catrin Pritchard, Dean Fennell.
      Malignant pleural mesothelioma (MPM) is an incurable cancer with a dismal prognosis and few effective treatment options. Nonetheless, recent positive phase III trial results for immune checkpoint blockade (ICB) in MPM herald a new dawn in the fight to advance effective treatments for this cancer. Tumor mutation burden (TMB) has been widely reported to predict ICB in other cancers, but MPM is considered a low-TMB tumor. Similarly, tumor programmed death-ligand 1 (PD-L1) expression has not been proven predictive in phase III clinical trials in MPM. Consequently, the precise mechanisms that determine response to immunotherapy in this cancer remain unknown. The present review therefore aimed to synthesize our current understanding of the tumor immune microenvironment in MPM and reflects on how specific cellular features might impact immunotherapy responses or lead to resistance. This approach will inform stratified approaches to therapy and advance immunotherapy combinations in MPM to improve clinical outcomes further.
    Keywords:  CD8-positive T lymphocytes; immunotherapy; lymphocytes; macrophages; tumor microenvironment; tumor-infiltrating
    DOI:  https://doi.org/10.1136/jitc-2021-003032
  2. World J Clin Oncol. 2021 Aug 24. 12(8): 581-608
    GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma.
    Javier Luna, Andrea Bobo, Joaquín José Cabrera-Rodriguez, María Pagola, Margarita Martín-Martín, María Ángeles González Ruiz, Miguel Montijano, Aurora Rodríguez, Lira Pelari-Mici, Almudena Corbacho, Marta Moreno, Felipe Couñago.
      Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis and rising incidence. Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement. Numerous therapeutic advances have been made in recent years, including the use of less aggressive surgical techniques associated with lower morbidity and mortality (e.g., pleurectomy/decortication), technological advancements in the field of radiotherapy (intensity-modulated radiotherapy, image-guided radiotherapy, stereotactic body radiotherapy, proton therapy), and developments in systemic therapies (chemotherapy and immunotherapy). These improvements have had as yet only a modest effect on local control and survival. Advances in the management of MPM and standardization of care are hampered by the evidence to date, limited by high heterogeneity among studies and small sample sizes. In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology, we review clinical, histologic, and therapeutic aspects of MPM, with a particular focus on all aspects relating to radiotherapy, including the current evidence base, associations with chemotherapy and surgery, treatment volumes and planning, technological advances, and reradiation.
    Keywords:  Chemotherapy; Malignant pleural mesothelioma; Radiation techniques; Radiotherapy; Reradiation; Surgery
    DOI:  https://doi.org/10.5306/wjco.v12.i8.581
  3. Clin Lung Cancer. 2021 Aug 10. pii: S1525-7304(21)00207-2. [Epub ahead of print]
    Treatment Patterns and Outcomes of Patients With Advanced Pleural Mesothelioma at an Academic Referral Centre.
    Sabine Schmid, Luna Zhan, Kristen Dietrich, Khaleeq Khan, Maisha Chowdhury, Michael Herman, Devalben Patel, Fatemeh Zaeimi, Natasha B Leighl, Adrian Sacher, Ronald Feld, Frances A Shepherd, Laura Donahoe, Marc de Perrot, Byoung Chun John Cho, Geoffrey Liu, Penelope A Bradbury.
       BACKGROUND: Overall survival (OS) for malignant pleural mesothelioma (MPM) in vulnerable subgroups remains poorly understood with scarce data available to guide treatment decisions. The study describes real-world detailed treatment patterns and outcomes of patients with advanced MPM overall and specifically in elderly and poor performance status (PS) patients.
    METHODS: Retrospective chart review was performed for all patients with histologically confirmed MPM seen at University Health Network/Princess Margaret Cancer Centre (UHN-PM).
    RESULTS: A total of 667 patients with MPM were identified and 304 advanced-disease MPM (aMPM) patients had continuing care at UHN-PM (UP-cohort). In the UP-cohort, 77% of patients received ≥ one line of systemic treatment. Systemic therapy trial participation was 39%. Patients not treated with systemic therapy (29%) were more likely to be ≥ 75 years and PS ≥ 2. Median OS was 15.3 months (95%CI 13.6-18.3), with longer survival in treated vs. untreated patients (17.4 vs. 10.6 months; P = .01). Longer survival with systemic treatment was seen in patients ≥75 years (12.7 vs. 6.6 months) and patients with poor PS (9.1 vs. 5.9 months). Median progression-free-survival (PFS) and OS for patients treated with second-line therapy was poor (3.0 and 8.9 months, respectively).
    DISCUSSION: In our real-world analysis of patients with aMPM treated at an academic referral centre, systemic treatment was given to the majority of patients and benefit was seen even in the elderly and poor PS patients frequently underrepresented in clinical trials. Trial participation was potentially facilitated by the formation of a dedicated multidisciplinary MPM clinic.
    Keywords:  Elderly; mesothelioma; multidisciplinary clinic; poor performance status; real-world analysis; systemic, treatment
    DOI:  https://doi.org/10.1016/j.cllc.2021.08.003
  4. Thorac Cancer. 2021 Sep 13.
    Evidence for marked underutilization of insurance billing in malignant pleural mesothelioma in Finland.
    Paulus Torkki, Juuso Paajanen, Ville Kytö, Sanna Laaksonen, Jari Räsänen, Marjukka Myllärniemi, Ilkka Ilonen.
       BACKGROUND: Substantial variation in health care costs for malignant pleural mesothelioma (MPM) has previously been identified.
    MATERIALS AND METHODS: We analyzed the changes in health care costs in MPM in Finland during 2002-2012. Finland has low-threshold public health care and a mandatory Workers' Compensation scheme that covers all occupational-related disease expenses. The costs include treatment costs for inpatients, hospice care, medication costs, rehabilitation costs, and travel costs. All costs are expressed in 2012 prices, adjusted using the consumer price index.
    RESULTS: A total of 907 MPM patients were included in the study. Mean duration of inpatient episodes increased 7% per year from 2002 to 2012, correlating with total costs (R2  = 0.861, p < 0.05). The annual total costs for treatment increased from 1.7 to 4.3 m€ during the study period and the cost per patient from 27 000 to 43 000 €. The overall costs increased progressively by the number of procedures performed. In patients who had been compensated for occupational cause by Workers' Compensation Center, only 36% of the overall care costs were billed from the insurance company. Billing of inpatient costs was 86% in these patients.
    CONCLUSION: During the study period, we found that the costs of MPM increased more than the average health care costs. This may be because of advanced diagnostic workup or more costly treatment (e.g., pemetrexed). Moreover, only one-third of all health care costs are charged to Workers' Compensation Insurance.
    Keywords:  asbestos; health care costs; malignant pleural mesothelioma; occupational disease
    DOI:  https://doi.org/10.1111/1759-7714.14146
  5. Int J Gen Med. 2021 ;14 4987-5003
    Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma.
    Dongli Xie, Jianchen Hu, Tong Wu, Kangli Cao, Xiaogang Luo.
       Background: Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM.
    Methods: Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers.
    Results: WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of >0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1).
    Conclusion: These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.
    Keywords:  carbon nanotubes; diagnosis; malignant pleural mesothelioma; malignant transformation; prognosis; tumor-infiltrating immune cells
    DOI:  https://doi.org/10.2147/IJGM.S324365
  6. Environ Health. 2021 Sep 15. 20(1): 103
    Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.
    C Airoldi, C Magnani, F Lazzarato, D Mirabelli, S Tunesi, D Ferrante.
       BACKGROUND: Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering.
    METHODS: A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed.
    RESULTS: One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5 km and 5-10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors.
    CONCLUSIONS: In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.
    Keywords:  Asbestos; Mesothelioma; Spatial analysis
    DOI:  https://doi.org/10.1186/s12940-021-00790-3
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