bims-mesote Biomed News
on Mesothelioma
Issue of 2022–04–24
nine papers selected by
Laura Mannarino, Humanitas Research
  1. Systemic treatment in patients with malignant pleural mesothelioma - real life experience.
  2. Clinical and molecular validation of BAP1, MTAP, P53, and Merlin immunohistochemistry in diagnosis of pleural mesothelioma.
  3. Feasibility of Tumor Treating Fields with Pemetrexed and Platinum-Based Chemotherapy for Unresectable Malignant Pleural Mesothelioma: Single-Center, Real-World Data.
  4. Diffuse Peritoneal Malignant Mesothelioma Presenting with Abnormal Uterine Bleeding: Case Report.
  5. [Research progress on the role of lncRNA in the occurrence and development of malignant mesothelioma].
  6. Molecular and Immunohistochemical Characterization of Mesothelioma of the Tunica Vaginalis.
  7. What has changed in malignant mesothelioma between 1990 and 2019? A time- series analyses in Turkey.
  8. Well differentiated papillary mesothelial tumor: a new name and new problems.
  9. How Our Continuing Studies of the Pre-clinical Inbred Mouse Models of Mesothelioma Have Influenced the Development of New Therapies.
  1. BMC Cancer. 2022 Apr 20. 22(1): 432
    Systemic treatment in patients with malignant pleural mesothelioma - real life experience.
    Barbara Ziółkowska, Bożena Cybulska-Stopa, Dimitrios Papantoniou, Rafał Suwiński.
       BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural cavity linked to asbestos exposure. The combination of pemetrexed and platinum is a standard first-line therapy for malignant pleural mesothelioma. Despite some progress, almost all MPM patients experience progression after first-line therapy. The second-line treatment is still being under discussion and there are very limited data available on the second-line and subsequent treatments.
    METHODS: The retrospective analysis included 57 patients (16 females and 41 males) from two Polish oncological institutions treated for advanced mesothelioma between 2013 and 2019. We analysed the efficacy of first-line and second-line therapy: progression-free survival (PFS), overall survival (OS), overall response rate (ORR).
    RESULTS: In the first-line treatment, 55 patients received pemetrexed-based chemotherapy (PBC) and two cisplatin in monotherapy. Patients' characteristics at baseline: median age was 64.2 years, ECOG PS ≤ 1 (86.2%), epithelial histology (85.7%). Median PFS and OS were 7.6 months and 14 months, respectively. Patients with ECOG PS ≤ 1 vs > 1 had a longer median OS (14.8 months vs 9.7 months, p = 0.057). One-year OS and PFS were 60.9% and 32.0%, respectively. Disease control rate (DCR) was 82.5%. Response to first-line therapy: PFS ≥ 6 months and PFS ≥ 12 months had a significant impact on median OS. Twelve patients received second-line therapy (seven PBC and five other cytotoxic single agents: navelbine, gemcitabine, or adriamycin/vincristine/methotrexate triplet). Median PFS and OS were 3.7 months and 7.2 months, respectively. DCR was 83%. One-year OS and PFS were 37% and 16.7%, respectively. In the group receiving PBC, OS was prolonged by 4.5 months compared to the non-PBC group (6.0 months vs 10.5 months, p = 0.47).
    CONCLUSION: Patients who benefited from first-line therapy and had prolonged PFS at first-line and achieve PFS longer than 6 months at first-line should be offered second-line treatment. Consideration of retreatment with the same cytotoxic agent could to be a viable option when no other treatment are available.
    Keywords:  Malignant pleural mesothelioma; Pemetrexed; Retreatment
    DOI:  https://doi.org/10.1186/s12885-022-09490-8
  2. Mod Pathol. 2022 Apr 22.
    Clinical and molecular validation of BAP1, MTAP, P53, and Merlin immunohistochemistry in diagnosis of pleural mesothelioma.
    David B Chapel, Jason L Hornick, Julianne Barlow, Raphael Bueno, Lynette M Sholl.
      BAP1 and MTAP immunostains play an important role in diagnosis of mesothelioma, but additional markers are needed to increase sensitivity. We analyzed 84 pleural mesotheliomas (51 epithelioid, 27 biphasic, 6 sarcomatoid) by a hybrid-capture next-generation sequencing (NGS) panel including complete coverage of coding and splicing regions for BAP1, CDKN2A/MTAP, NF2, and TP53 and correlated molecular findings with diagnostic immunostains for BAP1, MTAP, Merlin, and p53, respectively. Fifty-seven reactive mesothelial proliferations served as benign comparators. Loss of BAP1, MTAP, and Merlin protein expression were, respectively, 54%, 46%, and 52% sensitive and 100% specific for mesothelioma. Two-marker immunopanels of BAP1 + MTAP, BAP1 + Merlin, and MTAP + Merlin were 79%, 85%, and 71% sensitive for mesothelioma, while a three-marker immunopanel of BAP1 + MTAP + Merlin was 90% sensitive. Diffuse (mutant-pattern) p53 immunostaining was seen in only 6 (7%) tumors but represented the only immunohistochemical abnormality in 2 cases. Null-pattern p53 was not specific for malignancy. An immunopanel of BAP1 + MTAP + Merlin + p53 was 93% sensitive for mesothelioma, and panel NGS detected a pathogenic alteration in BAP1, MTAP, NF2, and/or TP53 in 95%. Together, 83 (99%) of 84 tumors showed a diagnostic alteration by either immunohistochemistry or panel NGS. Adding Merlin to the standard BAP1 + MTAP immunopanel increases sensitivity for mesothelioma without sacrificing specificity. p53 immunohistochemistry and panel NGS with complete coverage of BAP1, CDKN2A/MTAP, TP53, and NF2 may be useful in diagnostically challenging cases.
    DOI:  https://doi.org/10.1038/s41379-022-01081-z
  3. Cancers (Basel). 2022 Apr 16. pii: 2020. [Epub ahead of print]14(8):
    Feasibility of Tumor Treating Fields with Pemetrexed and Platinum-Based Chemotherapy for Unresectable Malignant Pleural Mesothelioma: Single-Center, Real-World Data.
    Tugce Kutuk, Haley Appel, Maria Carolina Avendano, Federico Albrecht, Paul Kaywin, Suyen Ramos, Melanie E Suarez-Murias, Minesh P Mehta, Rupesh Kotecha.
       PURPOSE: The objectives of this study were to evaluate the implementation, device usage rates, clinical outcomes, and treatment-related toxicities associated with TTFields and pemetrexed plus platinum-based chemotherapy in patients with unresectable MPM, outside the initial trial results.
    METHODS: Consecutive patients with unresectable MPM were enrolled onto an FDA-required HDE protocol from 2019 to 2021. All patients were treated with a protocol-defined regimen of continuous TTFields (150 kHz) and pemetrexed plus platinum-based chemotherapy.
    RESULTS: Five patients with unresectable MPM were enrolled. The median number of 4-week TTFields cycles was 5 (range: 2-7 cycles). Median TTFields device usage in the first 3 months was 12.5 h per day (range: 5-16.8 h), representing 52% (21-70%) of the potential daily duration. The median follow-up was 5.4 months (range: 1.1-20.9 months). Treatment-related dermatitis was the only side effect associated with TTFields and was reported as grade 1-2 in all patients; no patient had grade 3+ device-related toxicities.
    CONCLUSIONS: This study represents the first results of real-world implementation of TTFields for MPM. In comparison to the initial clinical trial (STELLAR), compliance rates were lower, although skin-related toxicities appeared similar. Further initiatives and guidelines should be developed to manage treatment-related dermatitis and improve device usage.
    Keywords:  compliance; dermatitis; malignant pleural mesothelioma; real world experience; skin adverse events; tumor treating fields (TTFields)
    DOI:  https://doi.org/10.3390/cancers14082020
  4. Case Rep Oncol. 2022 Jan-Apr;15(1):15(1): 251-256
    Diffuse Peritoneal Malignant Mesothelioma Presenting with Abnormal Uterine Bleeding: Case Report.
    Ivana Rizzuto, Theresa Power, Martin Klaus Oehler.
      This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who presented with abnormal menstrual bleeding due to diffuse infiltration of the uterus. MPM is a rare entity, which on initial clinical presentation can be indistinguishable from a primary gynecological malignancy such as ovarian cancer. As differential diagnosis is challenging among primary care physicians, gynecologists, gynecological oncologists, and pathologists, misdiagnosis and subsequent mismanagement are not uncommon. Immunohistochemical stains were required in our case to help to make the final diagnosis. We included multiple mesothelial markers such as calretinin, CK5/6, WT-1, and D240 in our analysis, in addition to epithelial markers such as Claudin-4, BerEP4, B72.3, and PAX-8, to exclude metastatic adenocarcinoma.
    Keywords:  Malignant peritoneal mesothelioma; Mesothelioma; Pleural mesothelioma
    DOI:  https://doi.org/10.1159/000522608
  5. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022 Mar 20. 40(3): 231-235
    [Research progress on the role of lncRNA in the occurrence and development of malignant mesothelioma].
    M Y Jin, Z Q Jiang.
      Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.
    Keywords:  Diagnosis; LncRNA; Mesothelioma; Prognosis
    DOI:  https://doi.org/10.3760/cma.j.cn121094-20210413-00205
  6. Histopathology. 2022 Apr 23.
    Molecular and Immunohistochemical Characterization of Mesothelioma of the Tunica Vaginalis.
    William J Anderson, Lynette M Sholl, Christopher D M Fletcher, Stephanie Schulte, Li Juan Wang, Fiona M Maclean, Michelle S Hirsch.
       AIMS: Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare and aggressive tumor, and the molecular features and staining profile with contemporary immunohistochemical (IHC) biomarkers are largely unexplored. We characterize the clinicopathologic, molecular, and IHC features of MM (N=13) and mesothelial neoplasms of uncertain malignant potential (MUMP) (N=4).
    METHODS AND RESULTS: Targeted next-generation sequencing was performed on 7 MMs and 2 MUMPs. IHC was performed for MTAP, BAP1 and SOX6. 13 adenomatoid tumors were also assessed with SOX6. MM were epithelioid (7/13) or biphasic (6/13). In MM, NF2 (5/7; 71%), CDKN2A (3/7; 43%), and BAP1 (2/7; 29%) were most frequently altered. Non-recurrent driver events were identified in PTCH1 and TSC1. In contrast, none of these alterations were identified in MUMPs; however, one MUMP harbored a TRAF7 missense mutation. By IHC, loss of MTAP (2/12; 17%) and BAP1 (2/9; 22%) was infrequent in MM, whereas both were retained in the MUMPs. SOX6 was positive in 9/11 (82%) MMs, and negative in all MUMPs and adenomatoid tumors.
    CONCLUSIONS: Testicular MM exhibit a similar mutational profile to those of the pleura/peritoneum; however, alterations in CDKN2A and BAP1 are less common. These findings suggest that although MTAP and BAP1 IHC are specific for MM, their sensitivity in testicular MMs appears lower. In addition, rare tumors may harbor targetable alterations in driver genes (PTCH1 and TSC1) that are unusual in MMs at other anatomic sites. SOX6 is sensitive for MM; accordingly, the presence of SOX6 expression argues against a benign neoplastic process.
    Keywords:  BAP1; MTAP; Mesothelioma; SOX6; adenomatoid; paratesticular; testis; tunica vaginalis
    DOI:  https://doi.org/10.1111/his.14669
  7. Int J Clin Oncol. 2022 Apr 21.
    What has changed in malignant mesothelioma between 1990 and 2019? A time- series analyses in Turkey.
    Selma Metintas, Guntulu Ak, Emine Dundar, Muzaffer Metintas.
       OBJECTIVES: To investigate the changes in epidemiological and survival characteristics of malignant mesothelioma (MM) cases diagnosed in a 30-year period between 1990 and 2019.
    METHODS: Data were analyzed considering three time periods (1990-1999, 2000-2009, 2010-2019) when treatment practices changed. The Join point Regression Program was used to analyze the change in clinical and epidemiological characteristics of the cases. Kaplan-Meier analysis was used to calculate the overall survival of the patients. Cox regression analysis was used to determine the effect of variables on survival.
    RESULTS: The study group consisted of 928 MM patients. During the study period, the mean age of the patients and the percentage of epithelioid subtype increased, while the percentage of female and histopathologically unidentified cases decreased. The median survival (95%CI) of patients according to the study periods was 9.0 (7.2-10.9), 9.0 (7.6-10.4) and 12.0 (10.5-13.5) months, respectively. A significant increase in overall survival was observed in the time trend (p = 0.013). There was no significant change in overall survival in patients receiving best supportive care over the 30-year period (p = 0.060), but an improvement of 1.4 (95%CI 0.2 to 2.7) months (p = 0.027) was observed in patient receiving chemotherapy. An improvement in overall survival of 4.8 (1.2 to 8.4) months was also observed in patients receiving multimodality treatment during 2000-2019 (p = 0.014). MM patients who were younger, female, diagnosed after 2000, epithelioid subtype, early stage, and received chemotherapy or multimodal treatment had longer survival.
    CONCLUSIONS: It was found that histopathological diagnosis and treatment success in MM have improved over the years.
    Keywords:  Chemotherapy; Histopathological diagnosis; Join point regression analysis; Malignant mesothelioma; Multimodality treatment
    DOI:  https://doi.org/10.1007/s10147-022-02168-y
  8. Mod Pathol. 2022 Apr 19.
    Well differentiated papillary mesothelial tumor: a new name and new problems.
    Andrew Churg, Francoise Galateau-Salle.
      Well-differentiated papillary mesothelial tumor (WDPMT, formerly called well-differentiated papillary mesothelioma) is a morphologically distinctive lesion composed of expansile papillae with a myxoid core covered by a single layer of generally bland mesothelial cells. Whether some WDPMT are precursors of invasive mesothelioma is uncertain, and this question is confounded by shallow biopsies of ordinary diffuse mesotheliomas that have superficial areas resembling WDPMT as well as by misinterpretation of some cases of mesothelioma in situ. Genetic analyses on a very small number of published cases of peritoneal WDPMT have shown a variety of mutations/copy number losses that do not overlap at all with those that are found recurrently in invasive mesotheliomas. The newly described entity of mesothelioma in situ usually appears as a single layer of mesothelial cells that have lost BAP1 by immunostaining, but sometimes is papillary and produces a morphologic mimic of WDPMT. We propose that, at least in the peritoneal cavity where most WDPMT occur, there are two morphologically identical but functionally distinct lesions: one is true WDPMT, a process that is probably benign, and the other is papillary mesothelioma in situ with the configuration of WDPMT. For that reason immunostaining for BAP1, and if necessary MTAP or CDKN2A FISH, should always be performed on cases with the appearance of WDPMT. It is possible, but speculative, that the small number of reports in the literature which describe invasive mesothelioma arising from WDMPT are actually describing invasive mesothelioma arising from mesothelioma in situ that looks like WDPMT.
    DOI:  https://doi.org/10.1038/s41379-022-01082-y
  9. Front Pharmacol. 2022 ;13 858557
    How Our Continuing Studies of the Pre-clinical Inbred Mouse Models of Mesothelioma Have Influenced the Development of New Therapies.
    Bruce W S Robinson, Alec J Redwood, Jenette Creaney.
      Asbestos-induced preclinical mouse models of mesothelioma produce tumors that are very similar to those that develop in humans and thus represent an ideal platform to study this rare, universally fatal tumor type. Our team and a number of other research groups have established such models as a stepping stone to new treatments, including chemotherapy, immunotherapy and other approaches that have been/are being translated into clinical trials. In some cases this work has led to changes in mesothelioma treatment practice and over the last 30 years these models and studies have led to trials which have improved the response rate in mesothelioma from less than 10% to over 50%. Mouse models have had a vital role in that improvement and will continue to play a key role in the future success of mesothelioma immunotherapy. In this review we focus only on these original inbred mouse models, the large number of preclinical studies conducted using them and their contribution to current and future clinical therapy for mesothelioma.
    Keywords:  asbestos; cancer; chemotherapy; immunothearpy; mesothelioma
    DOI:  https://doi.org/10.3389/fphar.2022.858557
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