bims-mesote Biomed News
on Mesothelioma
Issue of 2024–07–14
seven papers selected by
Laura Mannarino, Humanitas Research
  1. Treatment patterns and humanistic burden of malignant pleural mesothelioma in Spain.
  2. Major pathological response obtained after neoadjuvant chemotherapy combined with dual immunotherapy for malignant pleural mesothelioma: a case report.
  3. Spatial landscape of malignant pleural and peritoneal mesothelioma tumor immune microenvironment.
  4. Characterizing soluble immune checkpoint molecules and TGF-β1,2,3 in pleural effusion of malignant pleural mesothelioma.
  5. Real-World efficacy and safety of combination nivolumab plus ipilimumab for Untreated, Unresectable, pleural Mesothelioma: The Meso-Immune (GFPC 04-2021) trial.
  6. Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.
  7. Mortality in an Italian cohort of former asbestos cement workers.
  1. Clin Transl Oncol. 2024 Jul 06.
    Treatment patterns and humanistic burden of malignant pleural mesothelioma in Spain.
    Susana Cedres, Julio Calvete, Gavin Taylor-Stokes, Néstor Álvarez Ayerza, David Vilanova Larena, Melinda Daumont.
       PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer with long latency and poor prognosis. The real-world treatment patterns and humanistic burden of MPM in an international cohort of patients were recently published. Spanish data are currently lacking and are reported here.
    METHODS/PATIENTS: Data were collected from three sources: physician-abstracted demographic, clinical and treatment characteristics of patients with MPM; patient-completed questionnaires on treatment satisfaction, symptoms, caregiver use, and impact of the disease; and caregiver-completed questionnaire reporting their activity and its impact on their daily life.
    RESULTS: The 241 patients in Spain were primarily elderly (median age: 67 years), male, retired/unemployed/on long-term sick leave, and diagnosed at stage IV with unresectable disease. Exposure to asbestos was detected (54%, 101/188). First-line treatment (1L) consisted primarily of doublet chemotherapy (86%, 207/241). Of 102 patients who completed 1L at data abstraction, 67 were receiving maintenance therapy, most commonly singlet chemotherapy with pemetrexed. Best supportive care was given to 29 patients, primarily after 1L (86.2%, 25/29). Symptom burden was high and health-related quality of life was poor and declined with progression: mean (SD) EQ-5D score and EQ-5D visual analogue scale score were 0.615 (0.285) and 60.8 (17.1) in 1L and 0.497 (0.370) and 56.1 (19.5) in second line. Overall, 67% of patients (162/241) required daily assistance from their caregiver, who reported an impact on their psychological well-being.
    CONCLUSIONS: Patients with MPM in Spain were overall treated according to treatment guidelines at the time. Nevertheless, a considerable burden of disease was reported by patients and caregivers.
    Keywords:  Health-related quality of life; Malignant pleural mesothelioma; Spain; Treatment
    DOI:  https://doi.org/10.1007/s12094-024-03591-5
  2. Transl Lung Cancer Res. 2024 Jun 30. 13(6): 1420-1425
    Major pathological response obtained after neoadjuvant chemotherapy combined with dual immunotherapy for malignant pleural mesothelioma: a case report.
    Yuchen Zhang, Guangyin Zhao, Chen Xu, Jie Gu, Di Ge.
       Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking.
    Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment.
    Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.
    Keywords:  Malignant pleural mesothelioma (MPM); case report; double immunotherapy; major pathological response (MPR); neoadjuvant therapy
    DOI:  https://doi.org/10.21037/tlcr-24-195
  3. Cancer Res Commun. 2024 Jul 12.
    Spatial landscape of malignant pleural and peritoneal mesothelioma tumor immune microenvironment.
    Xiaojun Ma, David Lembersky, Elena S Kim, Michael J Becich, Joseph R Testa, Tullia C Bruno, Hatice U Osmanbeyoglu.
      Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence (mIF) analyses on tissue microarrays (n=3) from malignant peritoneal (MPeM, n=25) and pleural (MPM, n=88) mesothelioma patients. Our study aimed to elucidate spatial distributions of key immune cell populations and their association with LAG3, BAP1, NF2, and MTAP, with MTAP serving as a CDKN2A/B surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types with MM patient prognosis and clinical characteristics. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared to MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared to those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma (https://mesotheliomaspatialatlas.streamlit.app/), containing mIF and hematoxylin and eosin (H&E) images.
    DOI:  https://doi.org/10.1158/2767-9764.CRC-23-0524
  4. Sci Rep. 2024 Jul 10. 14(1): 15947
    Characterizing soluble immune checkpoint molecules and TGF-β1,2,3 in pleural effusion of malignant pleural mesothelioma.
    Riki Okita, Tomoya Senoo, Yuka Mimura-Kimura, Yusuke Mimura, Tomoyuki Murakami, Eiji Ikeda, Masanori Okada, Hidetoshi Inokawa, Keisuke Aoe.
      The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-β isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the levels of six molecules, clinicopathological characteristics, and efficacy of immune checkpoint inhibitors. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-β1, TGF-β2, and TGF-β3 were variably produced in PE of FP (n = 34) and MPM (n = 79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-β2 level in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-β1 and TGF-β3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.
    Keywords:  Immune checkpoint molecule; Mesothelioma; Pleural effusion; TGF-β; Tumor immune microenvironment
    DOI:  https://doi.org/10.1038/s41598-024-66189-5
  5. Lung Cancer. 2024 Jun 29. pii: S0169-5002(24)00400-8. [Epub ahead of print]194 107866
    Real-World efficacy and safety of combination nivolumab plus ipilimumab for Untreated, Unresectable, pleural Mesothelioma: The Meso-Immune (GFPC 04-2021) trial.
    GFPC
       BACKGROUND: First-line standard-of-care for unresectable, pleural mesothelioma (PM) changed with the phase 3 CheckMate 743 study results, showing that nivolumab plus ipilimumab (Nivo + Ipi) significantly extended overall survival (OS) versus platinum + pemetrexed chemotherapy for PM (median OS 18.1 versus 14.1 months; hazard ratio: 0.74; p = 0.002). Efficacy and safety data in real-world (rw) settings are needed to confirm these results.
    METHODS: This French multicenter, retrospective cohort study was undertaken to assess the outcomes of treatment-naïve PM patients given Nivo + Ipi via an early-access program (EAP). The primary objective was investigator-assessed real world -progression-free survival (PFS). The secondary objectives were the combination's -overall survival (OS) and safety.
    RESULTS: From 1 April 2021 to 15 Feb 2022, the analysis included 201 of the 305 EAP-enrolled patients treated in 63 centers (79.6 % men; median age: 75 years; 91.8 % Eastern Cooperative Oncology Group performance status (ECOG-PS) 0/1; 74.5 % epithelioid histology). With median (95 % CI) follow-up for all patients of 18.4 (17.7-19.2) months, -PFS and OS were 6.3 (5.3-7.5) and 18.9 (17.6-not reached (NR)) months, with 1-year OS at 66.4 % (60.1-73.3 %). Median OS and 1-year survival rates were 21.0 (18.7-NR) and 70.8 % (63.9 %-780.6 %), and 14.1 (10.9-21.0) months and 54.9 % (42.8 %-70.4 %) for epithelioid and non-epithelioid PM subgroups, respectively. PFS was equal between the two subgroups. Grade 3-4 adverse events occurred in 23.3 % of patients and three deaths were treatment-related.
    CONCLUSIONS: For this unselected PM population, efficacy and safety outcomes compared favorably with CheckMate 743 trial results.
    Keywords:  Immunotherapy; Pleural mesothelioma; Real-world data; Safety; Survival
    DOI:  https://doi.org/10.1016/j.lungcan.2024.107866
  6. Proc Natl Acad Sci U S A. 2024 Jul 16. 121(29): e2405231121
    Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.
    Flavia Novelli, Yoshie Yoshikawa, Veronica Angela Maria Vitto, Lorenzo Modesti, Michael Minaai, Sandra Pastorino, Mitsuru Emi, Jin-Hee Kim, Franz Kricek, Fang Bai, José N Onuchic, Angela Bononi, Joelle S Suarez, Mika Tanji, Cristina Favaron, Alicia A Zolondick, Ronghui Xu, Yasutaka Takanishi, Zhanwei Wang, Greg Sakamoto, Giovanni Gaudino, Joseph Grzymski, Federica Grosso, David S Schrump, Harvey I Pass, Lilit Atanesyan, Jan Smout, Suvi Savola, Kavita Y Sarin, Hassan Abolhassani, Lennart Hammarström, Qiang Pan-Hammarström, Carlotta Giorgi, Paolo Pinton, Haining Yang, Michele Carbone.
      We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 (BARD1) gene that were predicted to be damaging by computational analyses. We conducted functional assays, essential for accurate interpretation of missense variants, in primary fibroblasts that we established in tissue culture from a patient carrying the heterozygous BARD1V523A mutation. We found that these cells had genomic instability, reduced DNA repair, and impaired apoptosis. Investigating the underlying signaling pathways, we found that BARD1 forms a trimeric protein complex with p53 and SERCA2 that regulates calcium signaling and apoptosis. We validated these findings in BARD1-silenced primary human mesothelial cells exposed to asbestos. Our study elucidated mechanisms of BARD1 activity and revealed that heterozygous germline BARD1 mutations favor the development of mesothelioma and increase the susceptibility to asbestos carcinogenesis. These mesotheliomas are significantly less aggressive compared to mesotheliomas in asbestos workers.
    Keywords:  cancer prevention; carcinogenesis; gene × environment; genetics; mesothelioma
    DOI:  https://doi.org/10.1073/pnas.2405231121
  7. Ann Ist Super Sanita. 2024 Apr-Jun;60(2):60(2): 118-125
    Mortality in an Italian cohort of former asbestos cement workers.
    Amerigo Zona, Caterina Bruno, Achille Cernigliaro, Marco De Santis, Salvatore Scondotto, Lucia Fazzo.
       BACKGROUND: A pooled study on Italian asbestos cement plant cohorts observed mortality risk for asbestos-related diseases. This study analysed the mortality of workers cohort of an asbestos cement plant in Syracuse, Italy.
    METHODS: Workers' vital status and causes of death, during 1970-2018, were identified in regional health databases. Standardized mortality ratios (SMRs) by sex and temporal variables were calculated.
    RESULTS: Of the 900 cohort's subjects (636 men, 259 women, 5 unknown sex), for 867 the vital ascertainment was possible: 505 died during study period. All-cause mortality is similarly to the expected among men and lower among women. Pleural and lung malignant neoplasms (MN) exceeded in men (SMR=27.1, SMR=1.95), retroperitoneal and peritoneal MN in both sexes, no cases of larynx MN were observed. Mortality excess for ovarian MN (SMR=1.5) and asbestosis in both sexes (men: SMR=431.9, women: SMR=116.6) were found.
    CONCLUSIONS: Exceeding mortality from asbestos-related diseases, particularly in men was highlighted.
    DOI:  https://doi.org/10.4415/ANN_24_02_06
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