bims-mesote Biomed News
on Mesothelioma
Issue of 2021–08–01
eight papers selected by
Laura Mannarino, Humanitas Research
  1. Reconstruction of asbestos exposure in workers suffering from pleural neoplasms and employed in sectors not generally associated with high exposure levels: the importance of an accurate standardized assessment of occupational medicine.
  2. Blocking the GITR-GITRL pathway to overcome resistance to therapy in sarcomatoid malignant pleural mesothelioma.
  3. Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.
  4. Heterogeneity of treatment effects in malignant pleural mesothelioma.
  5. Comparative effectiveness of second-line immune checkpoint inhibitor therapy versus chemotherapy for malignant pleural mesothelioma.
  6. Heterogeneity of treatment effects in malignant pleural mesothelioma - Authors' reply.
  7. Primary Pericardial Mesothelioma: A Population-Based Propensity Score-Matched Analysis.
  8. Unusual case of malignant pleural mesothelioma.
  1. J Prev Med Hyg. 2021 Mar;62(1): E148-E151
    Reconstruction of asbestos exposure in workers suffering from pleural neoplasms and employed in sectors not generally associated with high exposure levels: the importance of an accurate standardized assessment of occupational medicine.
    Pasquale Scopa.
       Introduction: Malignant pleural mesothelioma onset in workers exposed to asbestos is well known with reference to multiple working sectors. In some cases, occurring among workers of sectors characterized by a presumed lower relevance of asbestos exposure, the absence of a well-defined correlation can prevent their emergence and compensation. To improve definition of these cases, this article underlines the importance of a standardized approach to occupational anamnesis.
    Methods: Thorough standardized occupational health assessment method application in a case of pleural malignant neoplasm occurred in a hauler, a job generally not associated with high levels of exposure to asbestos fibres.
    Results: Assessment of malignant pleural mesothelioma diagnosis and dual mode relevant occupational exposure to asbestos during both truck driving and loading and unloading operations of asbestos-containing goods.
    Conclusions: Systematic occupational medicine assessment with accurate standardized approach is essential for reconstruction of asbestos exposure, in order to highlight every aspect useful to establish causal link between cases of pleural mesothelioma and possible occupational and non-occupational exposure to the mineral, even in cases where the first-level occupational history does not appear to be suggestive.
    Keywords:  Asbestos; Pleural mesothelioma; Standardized occupational medicine assessment
    DOI:  https://doi.org/10.15167/2421-4248/jpmh2021.62.1.1334
  2. Commun Biol. 2021 Jul 26. 4(1): 914
    Blocking the GITR-GITRL pathway to overcome resistance to therapy in sarcomatoid malignant pleural mesothelioma.
    Meilin Chan, Licun Wu, Zhihong Yun, Trevor D McKee, Michael Cabanero, Yidan Zhao, Mikihiro Kohno, Junichi Murakami, Marc de Perrot.
      Malignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.
    DOI:  https://doi.org/10.1038/s42003-021-02430-5
  3. Acta Oncol. 2021 Jul 27. 1-7
    Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.
    Odd Terje Brustugun, Yngvar Nilssen, Inger Johanne Zwicky Eide.
       BACKGROUND: Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy.
    MATERIAL AND METHODS: Complete national data on 1509 pleural and peritoneal malignant mesothelioma from the Cancer Registry of Norway from 2000 to 2019 are presented. Age standardised incidence and median survival were calculated.
    RESULTS: The age-standardised incidence of pleural mesothelioma among males has decreased from 1.7 per 100 000 in 2000-2004 to 1.1 in 2015-2019, whereas the incidence for females has been stable, lower than 0.3 per 100 000 throughout the period. Incidence of peritoneal mesotheliomas remained low, below 0.08 per 100 000. The female to male ratio among pleural mesotheliomas was 1:7 with no differences among morphological subtypes, whereas this ratio was 1:1.2 in peritoneal mesotheliomas. Median age at diagnosis for pleural mesothelioma was 73 years and 76 years for females and males respectively in the last 5-year period, and 67 years for peritoneal mesotheliomas of both sexes. Median survival among pleural mesotheliomas has been stable, with significantly worse prognosis among sarcomatoid subtype (5.4 months) compared to epithelioid subtype (15.8 months). Peritoneal mesothelioma of the epithelioid subtype, representing 38% of cases, had a median survival of 43.3 months, contrasting the non-epithelioid subtype of 5.1 months.
    DISCUSSION: Mesothelioma is still a significant disease with a dismal prognosis. Improvement in treatment is warranted.
    Keywords:  Mesothelioma; peritoneal; pleural; population-based study; registry; survival
    DOI:  https://doi.org/10.1080/0284186X.2021.1955971
  4. Lancet. 2021 07 24. pii: S0140-6736(21)00882-5. [Epub ahead of print]398(10297): 301-302
    Heterogeneity of treatment effects in malignant pleural mesothelioma.
    Massimo Di Maio, Marco Tagliamento.
      
    DOI:  https://doi.org/10.1016/S0140-6736(21)00882-5
  5. Lung Cancer. 2021 Jul 17. pii: S0169-5002(21)00473-6. [Epub ahead of print]159 107-110
    Comparative effectiveness of second-line immune checkpoint inhibitor therapy versus chemotherapy for malignant pleural mesothelioma.
    Roger Y Kim, Yimei Li, Melina E Marmarelis, Anil Vachani.
       OBJECTIVES: Second-line immune checkpoint inhibition (ICI) was recently shown to have a survival advantage over placebo in malignant pleural mesothelioma (MPM), but the survival comparison to chemotherapy in patients with MPM receiving routine clinical care is unknown. Our objective was to examine the effectiveness of second-line ICI versus chemotherapy on overall survival (OS) outcomes in real-world patients with advanced MPM.
    MATERIALS AND METHODS: We performed a multicenter retrospective cohort study of real-world adult patients with advanced MPM who received first-line platinum-based chemotherapy and at least two total lines of systemic therapy. Patients received either second-line chemotherapy (gemcitabine and/or vinorelbine) or ICI therapy (pembrolizumab or nivolumab ± ipilimumab). The primary outcome was OS, defined as the time from second-line therapy initiation to death or end of the observation period. We used Kaplan-Meier methods and Cox proportional hazards modeling with adjustment for relevant patient demographic and clinical variables to compare OS between the two second-line treatment groups.
    RESULTS: Of the 176 patients with MPM, the median age was 75 years (IQR: 69-79.5 years), and most were white (77%), male (74%), and had epithelioid histology (67%). Thirty-five percent (61) received second-line chemotherapy and 65% (115) ICI therapy (80 pembrolizumab, 31 nivolumab, and 4 nivolumab + ipilimumab). Treatment with ICI was associated with significantly longer median OS compared to chemotherapy (8.7 vs 5.0 months, p=0.001; adjusted hazard ratio: 0.52, 95% CI: 0.34-0.81). The estimated 12-month OS probability was 36.7% (95% CI: 27.6%-45.8%) and 15.6% (95% CI: 7.7%-26.1%) in the ICI and chemotherapy groups, respectively.
    CONCLUSION: In this "real-world" population of patients with MPM, treatment with ICI was associated with improved OS outcomes compared to chemotherapy in the second-line setting, in contrast with a recent clinical trial. Our findings suggest that ICI may benefit patients with advanced MPM and progression after initial platinum-based chemotherapy.
    Keywords:  Immunotherapy; Mesothelioma; Survival
    DOI:  https://doi.org/10.1016/j.lungcan.2021.06.017
  6. Lancet. 2021 07 24. pii: S0140-6736(21)00876-X. [Epub ahead of print]398(10297): 302
    Heterogeneity of treatment effects in malignant pleural mesothelioma - Authors' reply.
    Paul Baas, Arnaud Scherpereel, Anna K Nowak, Abderrahim Oukessou, Gerard Zalcman.
      
    DOI:  https://doi.org/10.1016/S0140-6736(21)00876-X
  7. Semin Thorac Cardiovasc Surg. 2021 Jul 25. pii: S1043-0679(21)00332-4. [Epub ahead of print]
    Primary Pericardial Mesothelioma: A Population-Based Propensity Score-Matched Analysis.
    Hilliard Brydges, Kanhua Yin, Ramkumar Balasubramaniyan, Kyle W Lawrence, Rongkui Luo, Karl J Karlson, David B McAneny, Niloo M Edwards, Michael J Reardon, Nikola Dobrilovic.
      Primary pericardial mesothelioma is a rare malignancy of the mesothelial lining of the pericardium. This study aimed to evaluate the clinical characteristics and survival outcomes of these patients using a US population-based cancer database. We queried the Surveillance, Epidemiology, and End Results program (1973-2015). Primary pericardial mesothelioma patients with complete follow-up data were included, and primary pleural mesothelioma patients were identified as controls. Propensity-score matching was used to balance individual characteristics. Kaplan-Meier analysis and log-rank tests were performed to compare overall survival. Forty-one primary pericardial mesothelioma and 15,970 primary pleural mesothelioma patients were identified. Before matching, when compared to the pleural mesothelioma counterparts, primary pericardial mesothelioma patients were younger (median 57 vs. 73 years, p < 0.001), more likely to be female (46.3% vs. 20.2%, p < 0.001), more likely to be non-white (24.4% vs. 8.4%, p = 0.001), and less likely to have been diagnosed in the most recent study decade (2006-2015, 34.1% vs. 43.5%, p = 0.002). The overall one- and two-year survival rates were 22.0% and 12.2%, with a median survival of two months (IQR: 1-6). After 1:2 nearest neighbor propensity-score matching, 38 pericardial mesothelioma and 76 matched pleural mesothelioma cases were identified. The two matched groups had comparable baseline characteristics, including age, sex, race, year of diagnosis, histological type, and cancer history. Compared to their pleural mesothelioma counterparts, primary pericardial mesothelioma patients were less likely to receive chemotherapy (23.7% vs. 50.0%, p = 0.01) and had worse overall survival (median survival: two vs. ten months, log-rank p = 0.006). Primary pericardial mesothelioma has worse survival outcomes than pleural mesothelioma, with a median survival of only two months. These patients should seek care from experienced multidisciplinary teams at tertiary care centers that handle high volumes of mesothelioma patients.
    Keywords:  Pleural mesothelioma; Primary pericardial mesothelioma; Propensity score; SEER; Survival
    DOI:  https://doi.org/10.1053/j.semtcvs.2021.07.020
  8. BMJ Case Rep. 2021 Jul 28. pii: e243803. [Epub ahead of print]14(7):
    Unusual case of malignant pleural mesothelioma.
    Timothy Johanan Rajaratnam, Jurgen Herre.
      We present the case of a 65-year-old woman who presented with progressive dysphagia and was diagnosed with achalasia. She subsequently developed bilateral chylous pleural effusions, with no cause identified despite extensive investigations (including computed tomography (CT) scans, gastroscopy and medical thoracoscopy (MT)) and review at a dedicated pleural multidisciplinary team meeting.Despite optimal supportive management she deteriorated and was admitted to the intensive care unit, where she passed away due to sepsis and respiratory failure 10 months after initial presentation. A postmortem returned a diagnosis of epithelioid mesothelioma, encasing the carina, distal oesophagus and coeliac axis.Mesothelioma only very rarely presents with either chylous effusions or achalasia. Additionally while MT normally conveys excellent sensitivity for pleural malignancy, it was insufficient here. This case highlights how an unusually located mesothelioma can produce an unusual clinical picture. It also suggests a role for early video-assisted thoracoscopy to aid diagnosis.
    Keywords:  cancer intervention; gastroenterology; oncology; respiratory medicine
    DOI:  https://doi.org/10.1136/bcr-2021-243803
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