bims-mesote Biomed News
on Mesothelioma
Issue of 2022–11–20
nine papers selected by
Laura Mannarino, Humanitas Research
  1. ASO Author Reflections: Pleural Thickness in Patients with Malignant Pleural Mesothelioma.
  2. Imaging of Malignant Pleural, Pericardial, and Peritoneal Mesothelioma.
  3. Differentiating malignant pleural mesothelioma and metastatic pleural disease based on a machine learning model with primary CT signs: A multicentre study.
  4. Impact of Pleural Thickness on Occurrence of Postoperative Complications in Patients with Malignant Pleural Mesothelioma.
  5. A case report of breast metastasis from malignant pleural mesothelioma invading the rhabdoid muscle.
  6. Immune checkpoint inhibitors in lung tumors with rare histologies and other thoracic malignancies.
  7. Genomic and transcriptomic analysis of a diffuse pleural mesothelioma patient-derived xenograft library.
  8. Immune marker expression of irradiated mesothelioma cell lines.
  9. Pharmacokinetics of antibiotics for pleural infection.
  1. Ann Surg Oncol. 2022 Nov 16.
    ASO Author Reflections: Pleural Thickness in Patients with Malignant Pleural Mesothelioma.
    Shota Nakamura, Toshinari Ito, Toyofumi Fengshi Chen-Yoshikawa.
      
    DOI:  https://doi.org/10.1245/s10434-022-12844-y
  2. Adv Anat Pathol. 2022 Nov 18.
    Imaging of Malignant Pleural, Pericardial, and Peritoneal Mesothelioma.
    Chad D Strange, Edith M Marom, Jitesh Ahuja, Girish S Shroff, Gregory W Gladish, Brett W Carter, Mylene T Truong.
      Malignant mesothelioma is a rare tumor arising from the mesothelial cells that line the pleura, pericardium, peritoneum, and tunica vaginalis. Imaging plays a primary role in the diagnosis, staging, and management of malignant mesothelioma. Multimodality imaging, including radiography, computed tomography (CT), magnetic resonance imaging (MRI), and F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), is used in a variety of scenarios, including diagnosis, guidance for tissue sampling, staging, and reassessment of disease after therapy. CT is the primary imaging modality used in staging. MRI has superior contrast resolution compared with CT and can add value in terms of determining surgical resectability in equivocal cases. MRI can further assess the degree of local invasion, particularly into the mediastinum, chest wall, and diaphragm, for malignant pleural and pericardial mesotheliomas. FDG PET/CT plays a role in the diagnosis and staging of malignant pleural mesothelioma (MPM) and has been shown to be more accurate than CT, MRI, and PET alone in the staging of malignant pleural mesothelioma. PET/CT can also be used to target lesions for biopsy and to assess prognosis, treatment response, and tumor recurrence.
    DOI:  https://doi.org/10.1097/PAP.0000000000000386
  3. Heliyon. 2022 Nov;8(11): e11383
    Differentiating malignant pleural mesothelioma and metastatic pleural disease based on a machine learning model with primary CT signs: A multicentre study.
    Ye Li, Botao Cai, Bing Wang, Yan Lv, Wei He, Xiaoxia Xie, Dailun Hou.
       Rationale and Objectives: It is still a challenge to make confirming diagnosis of malignant pleural mesothelioma (MPM), especially differentiating from metastatic pleural disease (MPD). The aim of this study was to develop a model to distinguish MPM with MPD based on primary CT signs.
    Materials and methods: We retrospectively recruited 150 MPM patients and 147 MPD patients from two centers and assigned them to training (115 MPM patients and 113 MPD patients) and testing (35 MPM patients and 34 MPD patients) cohorts. The images were analyzed for pleural thickening, hydrothorax, lymphadenopathy, thoracic volume and calcified pleural plaque (CPP). The selected clinical characteristics and primary CT signs comprised the model by multivariate logistic regression in the training cohort. Then the model was tested on the external testing cohort. ROC curve and F1 score were used to validate the capability of the model in both two cohorts.
    Results: There were significant differences between two groups: (1) carcinoembryonic antigen (CEA); (2) nodular and mass pleural thickening; (3) the enhancement of pleura; (4) focal, diffuse and circumferential pleural thickening; (5) the thickest pleura; (6) thickening of diaphragmatic pleura; (7) multiple nodules and effusion of interlobar pleura; (8) hilar LN and ring enhancement of LN; (9) punctate and stipe CPP. The AUC and F1 score of the model were 0.970 and 0.857 in the training cohort, 0.955 and 0.818 in the testing cohort.
    Conclusion: The model holds promise for use as a diagnostic tool to distinguish MPM from MPD.
    Keywords:  Computer tomography; Machine learning; Malignant pleural mesothelioma; Metastatic pleural disease
    DOI:  https://doi.org/10.1016/j.heliyon.2022.e11383
  4. Ann Surg Oncol. 2022 Nov 13.
    Impact of Pleural Thickness on Occurrence of Postoperative Complications in Patients with Malignant Pleural Mesothelioma.
    Toshinari Ito, Shota Nakamura, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Naoki Ozeki, Koichi Fukumoto, Toyofumi Fengshi Chen-Yoshikawa.
       OBJECTIVES: The rates of postoperative mortality and morbidity are high in patients with malignant pleural mesothelioma (MPM). Therefore, it is important to identify variables that increase the risk of postoperative complications. Pleural thickness has recently been identified as a prognostic indicator in patients with MPM. The aim of this study was to investigate clinical variables, including pleural thickness, that contribute to postoperative complications in patients with MPM.
    PATIENTS AND METHODS: A total of 47 patients who underwent surgical excision of MPM between 2005 and 2021 were enrolled in this study. Correlations between postoperative complications within 90 days of surgery and preoperative clinical factors were investigated.
    RESULTS: A total of 27 patients underwent extrapleural pneumonectomy (EPP), and the remaining 20 underwent pleurectomy/decortication (P/D). Macroscopic complete resections were obtained in all but three patients. Of the 47 patients, 23 (49%) experienced postoperative complications of grade 3 or worse. The major complication in patients with EPP was respiratory failure (n = 6), whereas the major complication in patients with P/D was prolonged air leakage (n = 7). Univariate logistic regression analysis found a correlation between postoperative complications and age, surgical side, and pleural thickness, while multivariate logistic regression analysis found surgical side (p = 0.04, 95% Cl 1.10-21.71, OR 4.90) and pleural thickness (p = 0.03, 95% Cl 1.21-23.00, OR 5.26) to significantly influence the occurrence of postoperative complications.
    CONCLUSIONS: Pleural thickness has a significant effect on the occurrence of postoperative complications. Patients with thick pleura on the right side are at greater risk of postoperative complications.
    DOI:  https://doi.org/10.1245/s10434-022-12790-9
  5. Asian J Surg. 2022 Nov 11. pii: S1015-9584(22)01572-X. [Epub ahead of print]
    A case report of breast metastasis from malignant pleural mesothelioma invading the rhabdoid muscle.
    Lingxin Kong, Dahu Ren, Shuangqing Chen, Guochen Duan.
      
    DOI:  https://doi.org/10.1016/j.asjsur.2022.11.025
  6. Immunotherapy. 2022 Nov 16.
    Immune checkpoint inhibitors in lung tumors with rare histologies and other thoracic malignancies.
    Elisa Andrini, Alessandro Di Federico, Monia Sisi, Matteo Rosellini, Arianna Palladini, Giuseppe Lamberti, Andrea De Giglio, Francesco Gelsomino.
      In recent years, immunotherapy has significantly changed the treatment of locally advanced/metastatic non-small-cell lung cancer (NSCLC). Conversely, the role of immunotherapy in NSCLC with uncommon histologies remains unclear, while in other rare thoracic malignancies, such as malignant pleural mesothelioma and thymic epithelial tumors, the use of immune checkpoint inhibitors is modifying therapeutic strategies with solid hopes for the future. However, larger prospective studies are urgently needed to define the best treatment strategies and the role of immunotherapy in these orphan tumors. This review provides a comprehensive overview of the emerging role of immunotherapy in the treatment of patients affected by these rare thoracic malignancies.
    Keywords:  NSCLC; PD-(L)1 inhibitor; malignant pleural mesothelioma; rare histologies; thymic epithelial tumors
    DOI:  https://doi.org/10.2217/imt-2022-0060
  7. Genome Med. 2022 Nov 15. 14(1): 127
    Genomic and transcriptomic analysis of a diffuse pleural mesothelioma patient-derived xenograft library.
    Michael Offin, Jennifer L Sauter, Sam E Tischfield, Jacklynn V Egger, Shweta Chavan, Nisargbhai S Shah, Parvathy Manoj, Katia Ventura, Viola Allaj, Elisa de Stanchina, William Travis, Marc Ladanyi, Andreas Rimner, Valerie W Rusch, Prasad S Adusumilli, John T Poirier, Marjorie G Zauderer, Charles M Rudin, Triparna Sen.
       BACKGROUND: Diffuse pleural mesothelioma (DPM) is an aggressive malignancy that, despite recent treatment advances, has unacceptably poor outcomes. Therapeutic research in DPM is inhibited by a paucity of preclinical models that faithfully recapitulate the human disease.
    METHODS: We established 22 patient-derived xenografts (PDX) from 22 patients with DPM and performed multi-omic analyses to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these PDX models and compared features to those of the matched primary patient tumors. Targeted next-generation sequencing (NGS; MSK-IMPACT), immunohistochemistry, and histologic subtyping were performed on all available samples. RNA sequencing was performed on all available PDX samples. Clinical outcomes and treatment history were annotated for all patients. Platinum-doublet progression-free survival (PFS) was determined from the start of chemotherapy until radiographic/clinical progression and grouped into < or ≥ 6 months.
    RESULTS: PDX models were established from both treatment naïve and previously treated samples and were noted to closely resemble the histology, genomic landscape, and proteomic profiles of the parent tumor. After establishing the validity of the models, transcriptomic analyses demonstrated overexpression in WNT/β-catenin, hedgehog, and TGF-β signaling and a consistent suppression of immune-related signaling in PDXs derived from patients with worse clinical outcomes.
    CONCLUSIONS: These data demonstrate that DPM PDX models closely resemble the genotype and phenotype of parental tumors, and identify pathways altered in DPM for future exploration in preclinical studies.
    DOI:  https://doi.org/10.1186/s13073-022-01129-4
  8. Front Oncol. 2022 ;12 1020493
    Immune marker expression of irradiated mesothelioma cell lines.
    Faith Chang, Synat Keam, Tracy Seymour Hoang, Jenette Creaney, Suki Gill, Anna K Nowak, Martin Ebert, Alistair M Cook.
       Background: Though immune checkpoint inhibition has recently shown encouraging clinical efficacy in mesothelioma, most patients do not respond. Combining immune checkpoint inhibition with radiotherapy presents an attractive option for improving treatment responses owing to the various immunomodulatory effects of radiation on tumors. However, the ideal dosing and scheduling of combined treatment remains elusive, as it is poorly studied in mesothelioma. The present study characterizes the dose- and time-dependent changes to expression of various immune markers and cytokines important to antitumor responses following irradiation of mesothelioma cell lines.
    Methods: Two murine (AB1, AE17) and two human (BYE, JU77) mesothelioma cell lines were treated with titrated gamma-radiation doses (1-8 Gy) and the expression of MHC class-I, MHC class-II and PD-L1 was measured over a series of post-irradiation timepoints (1-72 hours) by flow cytometry. Levels of cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β, IFN-γ, TNF-α, and GM-CSF were measured by multiplex immunoassay in murine cell lines following 8 Gy radiation.
    Results: Following irradiation, a dose-dependent upregulation of MHC-I and PD-L1 was observed on three of the four cell lines studied to varying extents. For all cell lines, the increase in marker expression was most pronounced 72 hours after radiation. At this timepoint, increases in levels of cytokines IFN-β, MCP-1 and IL-6 were observed following irradiation with 8 Gy in AB1 but not AE17, reflecting patterns in marker expression.
    Conclusions: Overall, this study establishes the dose- and time-dependent changes in immune marker expression of commonly studied mesothelioma cell lines following radiation and will inform future study into optimal dosing and scheduling of combined radiotherapy and immune checkpoint inhibition for mesothelioma.
    Keywords:  MHC; PD-L1; immune checkpoint inhibition; mesothelioma; radiotherapy
    DOI:  https://doi.org/10.3389/fonc.2022.1020493
  9. Expert Rev Respir Med. 2022 Nov 15.
    Pharmacokinetics of antibiotics for pleural infection.
    E P M Lau, Calvinjit Sidhu, Natalia D Popowicz, Y C Gary Lee.
       INTRODUCTION: Pleural infection causes significant morbidity and mortality. An important aspect in the treatment of pleural infection is the pharmacokinetics of antibiotics, an area often neglected.
    AREAS COVERED: Pathophysiology of pleural infection and the importance of antibiotic therapy in the treatment of pleural infection are discussed. After reviewing all available literature on pharmacokinetics of antibiotics for pleural infection, the scarcity of data and knowledge gaps are highlighted.
    EXPERT OPINION: This review aims to heighten awareness of the limited pharmacokinetic data of commonly used antibiotics for pleural infection. It serves to remind clinicians that choice of antibiotics for pleural infection should be based not only on bacterial sensitivity but also adequate delivery of antibiotics to the infected pleural cavity. Antibiotic pharmacokinetics may vary with agents used, pleural thickness and individual characteristics. Consideration must be given to insufficient pleural delivery of systemic antibiotics in patients lacking clinical improvement.
    Pleural infection research has disproportionately focused on fluid drainage. Optimizing delivery of effective antibiotic therapy to the pleural cavity must be regarded a key priority to progress clinical care. Large comprehensive cohort studies on pharmacokinetic variability are the essential next step. The possibility of intrapleural administration is also an area that warrants additional research.
    Keywords:  antibiotics; infection; pharmacokinetics; pleural
    DOI:  https://doi.org/10.1080/17476348.2022.2147508
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