bims-mesote Biomed News
on Mesothelioma
Issue of 2022–09–04
seven papers selected by
Laura Mannarino, Humanitas Research
  1. Circulating biomarkers in malignant pleural mesothelioma.
  2. A case of brain metastasis with pathological transformation of long-surviving malignant pleural mesothelioma: illustrative case.
  3. IL-7 is expressed in malignant mesothelioma and has a prognostic value.
  4. Meta-analysis of survival after extrapleural pneumonectomy (EPP) versus pleurectomy/decortication (P/D) for malignant pleural mesothelioma in the context of macroscopic complete resection (MCR).
  5. Prognostic risk assessment model for alternative splicing events and splicing factors in malignant pleural mesothelioma.
  6. Feasibility and safety of extended pleurectomy/decortication for malignant pleural mesothelioma. A single group experience.
  7. Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC.
  1. Explor Target Antitumor Ther. 2020 ;1(6): 434-451
    Circulating biomarkers in malignant pleural mesothelioma.
    Giuseppe Viscardi, Davide Di Natale, Morena Fasano, Marta Brambilla, Riccardo Lobefaro, Alessandro De Toma, Giulia Galli.
      Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.
    Keywords:  CTC; Mesothelioma; biomarkers; ctDNA; liquid biopsy; malignant pleural mesothelioma; mesothelin; miRNAs
    DOI:  https://doi.org/10.37349/etat.2020.00028
  2. J Neurosurg Case Lessons. 2021 Jan 18. 1(3): CASE2099
    A case of brain metastasis with pathological transformation of long-surviving malignant pleural mesothelioma: illustrative case.
    Ryuichi Noda, Shunsuke Yanagisawa, Masato Inoue, Tetsuo Hara.
       BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer, and in 80% of cases the cause is asbestos exposure. In 1972, the World Health Organization (WHO) declared asbestos is a carcinogenic substance. Since then, every developed country has restricted and banned the product. Because of its high heat resistance, asbestos had been widely used as building material for decades. The WHO estimated that approximately 125 million people are exposed to asbestos, and more than 107,000 die from asbestos-related diseases annually. Because of its long incubation period, the number of patients is estimated to keep increasing in the near future.
    OBSERVATIONS: The authors report a case of long-surviving MPM with a rushed clinical course after brain metastasis. A 69-year-old woman diagnosed with MPM (epithelial type) 6 years earlier presented with a brain metastasis. The pathological result of the brain metastasis was the sarcomatoid type. This case showed the possibility of subtype transition after long survival.
    LESSONS: This article aids in understanding the long-term natural history of MPM and the possibility of epithelial-mesenchymal transition. Neurosurgeons have to be aware of its the natural history and the possibility of brain metastasis.
    Keywords:  EMT = epithelial-mesenchymal transition; IMRT = intensity-modulated radiation therapy; MPM = malignant pleural mesothelioma; MRI = magnetic resonance imaging; PEM = pemetrexed; WHO = World Health Organization; asbestos; brain metastasis; epithelial-mesenchymal transition; malignant pleural mesothelioma
    DOI:  https://doi.org/10.3171/CASE2099
  3. Mol Oncol. 2022 Aug 28.
    IL-7 is expressed in malignant mesothelioma and has a prognostic value.
    Hoa-Le Mai, Sophie Deshayes, Thi-Van-Ha Nguyen, Virginie Dehame, Anne-Laure Chéné, Sophie Brouard, Christophe Blanquart.
      Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL-7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL-7R/IL-7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL-7R, IL-7 had no effect on their intracellular signalling. Accordingly, the addition of IL-7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumours was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL-7 concentration was not a good diagnostic biomarker. However, we observed that high IL-7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL-7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL-7R/IL-7 signalling pathway is not functional in MPM cells, IL-7 expression in PEs may have prognostic value in MPM patients.
    Keywords:  IL-7; IL-7R; Mesothelioma; biomarker; pleural fluids
    DOI:  https://doi.org/10.1002/1878-0261.13310
  4. Updates Surg. 2022 Sep 03.
    Meta-analysis of survival after extrapleural pneumonectomy (EPP) versus pleurectomy/decortication (P/D) for malignant pleural mesothelioma in the context of macroscopic complete resection (MCR).
    Dimitrios E Magouliotis, Prokopis-Andreas Zotos, Arian Arjomandi Rad, Despoina Koukousaki, Vasiliki Vasilaki, Ioustini Portesi, Kyriakos Spiliopoulos, Thanos Athanasiou.
       OBJECTIVE: We reviewed the available literature on patients with MPM undergoing either extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D).
    METHODS: Original research studies that evaluated long-term outcomes of P/D versus EPP were identified, from January 1980 to February 2022. The 30-days and 90-day mortality, along with the 1-, 2-, 3-, 5-year survival, the median overall survival, the macroscopic complete resection (MCR) rate, and the complications were calculated according to both a fixed and a random effect model. The Q and I2 statistic were used to test for heterogeneity among the studies. Sensitivity analysis was performed including only studies that incorporated the MCR concept.
    RESULTS: Eighteen studies were included, incorporating a total of 4,852 patients treated with EPP and P/D. The 30-day mortality was significantly higher in the EPP group (OR: 2.79 [95% CI 1.30, 6.01]; p = 0.009). The median overall survival was higher in the P/D group (WMD:-4.55 [-6.05, -3.04]; p < 0.001). No differences were found regarding the 90-day mortality, MCR rate, and the 1-, 2-,3-, 5-year survival between the EPP and P/D groups. These findings were validated by the sensitivity analysis. The incidence of atrial fibrillation, hemorrhage, pulmonary embolism, air leak, and reoperation was significantly increased in the EPP group (p < 0.05).
    CONCLUSIONS: The present meta-analysis indicates that P/D is associated with enhanced outcomes regarding 30-day mortality, median overall survival, and complications. The P/D approach should be preferred when technically feasible. However, the procedure of choice should be decided based on the goal of MCR in the safest approach for the patient.
    Keywords:  Decortication; Extrapleural pneumonectomy; Macroscopic complete resection; Malignant pleural mesothelioma; Pleurectomy
    DOI:  https://doi.org/10.1007/s13304-022-01369-4
  5. Cancer Med. 2022 Aug 28.
    Prognostic risk assessment model for alternative splicing events and splicing factors in malignant pleural mesothelioma.
    Yue Jiang, Chengda Zhang, Yang Chen, Shiyu Zhao, Yipeng He, Jun He.
       BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and highly malignant thoracic tumor. Although alternative splicing (AS) is associated with tumor prognosis, the prognostic significance of AS in MPM is unknown.
    METHODS: Transcriptomic data, clinical information, and splicing percentage values for MPM were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analyses were performed to establish a model affecting the prognosis of MPM. Survival and ROC analyses were used to test the effects of the prognostic model. LASSO/multivariate Cox analysis was used to construct the MPM prognostic splicing factor (SF) model. The SF-AS interaction network was analyzed using Spearman correlation and visualized using Cytoscape. The association between the MPM prognostic SF model and drug sensitivity to chemotherapeutic agents such as cisplatin was analyzed using pRRophetic.R.
    RESULTS: The LASSO/multivariate Cox analysis identified 41 AS events and 2 SFs that were mostly associated with survival. Nine prognostic prediction models (i.e., seven types of AS model, total AS model, and SF model) were developed. An MPM prognostic SF-AS regulatory network was subsequently constructed with decreased drug sensitivity in the SF model high-risk group (p = 0.025).
    CONCLUSION: This study provides the first comprehensive analysis of the prognostic value of AS events and SFs in MPM. The SF-AS regulatory network established in this study and our drug sensitivity analysis using the SF model may provide novel targets for pharmacological studies of MPM.
    DOI:  https://doi.org/10.1002/cam4.5174
  6. Thorac Cancer. 2022 Sep 02.
    Feasibility and safety of extended pleurectomy/decortication for malignant pleural mesothelioma. A single group experience.
    Francesco Falanga, Pietro Rinaldi, Cristiano Primiceri, Chandra Bortolotto, Olga Oneta, Francesco Agustoni, Patrizia Morbini, Laura Saracino, Dimitrios Eleftheriou, Federico Sottotetti, Giulia Maria Stella.
      Surgery is part of a multimodal therapeutic approach to malignant pleural mesothelioma (MPM) although its real beneficial effect is still controversial. The optimal precise sequence of treatments within the trimodality is unclear, and should be decided upon a multidisciplinary consensus for each individual patient. Here, we analyzed the perioperative data of 19 MPM patients who underwent extended pleurectomy/decortication (EPD) with curative intent. The mean age at diagnosis was 67 years; 11 males and eight females. Ten patients were diagnosed with MPM via medical thoracoscopy (MT), and nine via video-assisted thoracoscopic surgery (VATS). The vast majority of cases harbored epitheliod forms. We compared neoadjuvant chemotherapy (NCT) followed by surgery (11 cases) versus surgery followed by adjuvant chemotherapy (ACT, 8 cases) within a 3-year period. All patients had extended pleurectomy/decortication and none had an extended pneumonectomy. Analysis of survival curves suggested that the short-term outcomes are better with upfront EDP followed by ACT if compared to EDP preceded by NCT. Although limited, the data highlighted the safety and feasibility of EPD, with manageable postoperative complications and no major burden for the patients.
    Keywords:  malignant pleural mesothelioma; multidisciplinary; pleurectomy
    DOI:  https://doi.org/10.1111/1759-7714.14627
  7. Explor Target Antitumor Ther. 2021 ;2(1): 1-25
    Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC.
    Luca Cantini, Federica Pecci, Filippo Merloni, Andrea Lanese, Edoardo Lenci, Francesco Paoloni, Joachim G J V Aerts, Rossana Berardi.
      The introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in patient prognosis. Disappointingly, the success of ICI therapy in NSCLC has not been fully replicated in other thoracic malignancies as small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM), and thymic epithelial tumors (TETs), due to the peculiar biological features of these disease and to the difficulties in the conduction of well-designed, biomarker-driven clinical trials. Therefore, combination strategies of ICIs plus conventional therapies (either chemotherapy, alternative ICIs or targeted agents) have been implemented. Although first approvals of ICI therapy have been recently granted in SCLC and MPM (in combination with chemotherapy and different ICIs), results remain somewhat modest and limited to a small proportion of patients. This work reviews the trial results of ICI therapy in mesothelioma, SCLC, and TETs and discusses the potential of combining ICIs with old drugs.
    Keywords:  Immune checkpoint inhibitors; immune modulating; immuno-oncology; mesothelioma; small cell lung cancer; thymic epithelial tumor
    DOI:  https://doi.org/10.37349/etat.2021.00030
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