bims-mesote Biomed News
on Mesothelioma
Issue of 2024–06–23
eight papers selected by
Laura Mannarino, Humanitas Research
  1. Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.
  2. Comprehensive Pulmonary Rehabilitation for Patients with Malignant Pleural Mesothelioma: A Feasibility Pilot Study.
  3. The Pleural Mesothelioma Cases and Mortality in Portugal in 2014-2020: A Descriptive Study.
  4. Evaluation of the combination of gemcitabine, carboplatin, and lactate dehydrogenase A inhibitor on malignant mesothelioma.
  5. Targeted Therapy in Mesotheliomas: Uphill All the Way.
  6. The past, present, and future of targeted therapeutic approaches in patients with diffuse pleural mesotheliomas.
  7. Rethinking continuity in primary care for people with mesothelioma.
  8. NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity.
  1. Oncotarget. 2024 Jun 20. 15 408-417
    Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.
    Kazuhiro Kitajima, Kozo Kuribayashi, Toshiyuki Minami, Hiroyuki Yokoyama, Akifumi Nakamura, Masaki Hashimoto, Takashi Kijima, Seiki Hasegawa, Hayato Kaida, Koichiro Yamakado.
       OBJECTIVES: Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST (imPERCIST), shown by [18F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and modified RECIST (mRECIST), shown by CT, were compared for response evaluation and prognosis prediction.
    RESULTS: imPERCIST indicated nine progressive metabolic disease (PMD), eight stable metabolic disease (SMD), four partial metabolic response (PMR), and five complete metabolic response (CMR) cases. mRECIST showed nine with progressive disease (PD), nine stable disease (SD), seven partial response (PR), and one complete response (CR). Although high concordance was noted (κ = 0.827), imPERCIST correctly judged a greater percentage with CMR (15.4%). Following a median 10.0 months, 15 patients showed progression and eight died from MPM. With both, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients without progression (CMR/PMR/SMD, CR/PR/SD, respectively) as compared to PMD/PD patients (imPERCIST p < 0.0001 and p = 0.015, respectively; mRECIST p < 0.0001 and p = 0.015, respectively).
    METHODS: Twenty-six patients (23 males, 3 females; median 73.5 years) with histologically proven MPM and no curative surgery received nivolumab plus ipilimumab combination therapy. FDG-PET/CT and diagnostic CT scanning at the baseline, and after 2-4 cycles (2 in three, 3 in 17, 4 in six patients) were performed. Therapeutic response findings evaluated using imPERCIST and mRECIST were compared. PFS and OS analyses were done using log-rank and Cox methods.
    CONCLUSION: For unresectable MPM patient examinations, FDG-PET and CT provide accurate findings for evaluating tumor response and also prognosis prediction following first-line nivolumab plus ipilimumab immunotherapy (approximately three cycles).
    Keywords:  FDG (fluorodeoxyglucose); PET-CT (positron emission tomography-computed tomography); immunotherapy; immunotherapy-modified PERCIST (positron emission tomography response criteria in solid tumors); mesothelioma
    DOI:  https://doi.org/10.18632/oncotarget.28594
  2. Cancers (Basel). 2024 May 26. pii: 2023. [Epub ahead of print]16(11):
    Comprehensive Pulmonary Rehabilitation for Patients with Malignant Pleural Mesothelioma: A Feasibility Pilot Study.
    Lorenzo Lippi, Alessandro de Sire, Arianna Folli, Claudio Curci, Dario Calafiore, Mariano Lombardi, Luca Bertolaccini, Alessio Turco, Antonio Ammendolia, Nicola Fusco, Lorenzo Spaggiari, Marco Invernizzi.
      Malignant pleural mesothelioma (MPM) represents a significant health burden, with limited treatment options and poor prognosis. Despite advances in pharmacological and surgical interventions, the role of rehabilitation in MPM management remains underexplored. This study aims to assess the feasibility of a tailored pulmonary rehabilitation intervention addressing physical and respiratory function in MPM patients. A prospective pilot study was conducted on surgically treated MPM patients referred to a cardiopulmonary rehabilitation service. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. However, some issues, such as time constraints and lack of continuous supervision, were reported by participants. This pilot study demonstrates the feasibility and potential benefits of a tailored pulmonary rehabilitation intervention in MPM patients. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM.
    Keywords:  complementary treatment; malignant pleural mesothelioma; muscle; physical exercise; physical function; rehabilitation
    DOI:  https://doi.org/10.3390/cancers16112023
  3. Healthcare (Basel). 2024 May 28. pii: 1103. [Epub ahead of print]12(11):
    The Pleural Mesothelioma Cases and Mortality in Portugal in 2014-2020: A Descriptive Study.
    Cátia Santos, Ema Sacadura-Leite, Joana Ferreira, Maria Dos Anjos Dixe, Philippe Astoul, António Sousa-Uva.
       BACKGROUND: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known.
    OBJECTIVE: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020.
    METHODS: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System.
    RESULTS: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%).
    CONCLUSION: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases.
    Keywords:  asbestos; exposure; incidence; malignant mesothelioma; mortality; pleural mesothelioma; years of life loss
    DOI:  https://doi.org/10.3390/healthcare12111103
  4. Nucleosides Nucleotides Nucleic Acids. 2024 Jun 20. 1-8
    Evaluation of the combination of gemcitabine, carboplatin, and lactate dehydrogenase A inhibitor on malignant mesothelioma.
    Marika A Frańczak, Federica Borea, Ryszard T Smoleński, Carlotta Granchi, Filippo Minutolo, Elisa Giovannetti, Godefridus J Peters.
       OBJECTIVES: Lactate dehydrogenase A (LDH-A) catalyzes the last step of glycolysis: supplying cells rapidly but inefficiently with ATP. Many tumors, including malignant mesothelioma (MM), have a high expression of LDH-A, which is associated with cancer aggressiveness. We aimed to determine whether the efficacy of the gemcitabine/carboplatin (Gem + Carbo) combination, widely used to treat this disease, could be increased by inhibition of LDH-A (by NHI-2). To this aim, we analyzed the growth inhibition of pleural and peritoneal MM by multiple combinations.
    METHODS: The 72 h sulforhodamine B assay (SRB) was used to test the cytotoxicity of the combination of gemcitabine (in the range 0.1 - 400 nM) and carboplatin (0.01 - 40 µM) with a fixed concentration of NHI-2 (at IC25). We used pleural (H2452) and primary peritoneal (STO, MESO-II) MM cell lines, cultured at normoxic conditions.
    RESULTS: NHI-2 did not increase the cytotoxicity of the combination of 100 nM gemcitabine and 10 µM carboplatin in peritoneal MM cell lines. The cell growth inhibition was 10% smaller after the triple combination than the Gem + Carbo treatment.
    CONCLUSIONS: Inhibition of LDH-A did not increase the efficacy of gemcitabine and carboplatin in MM under normoxic conditions.
    Keywords:  Lactate dehydrogenase A inhibitor; carboplatin; gemcitabine; malignant mesothelioma
    DOI:  https://doi.org/10.1080/15257770.2024.2356201
  5. Cancers (Basel). 2024 May 22. pii: 1971. [Epub ahead of print]16(11):
    Targeted Therapy in Mesotheliomas: Uphill All the Way.
    Elisa Bertoli, Elisa De Carlo, Martina Bortolot, Brigida Stanzione, Alessandro Del Conte, Michele Spina, Alessandra Bearz.
      Mesothelioma (MM) is an aggressive and lethal disease with few therapeutic opportunities. Platinum-pemetrexed chemotherapy is the backbone of first-line treatment for MM. The introduction of immunotherapy (IO) has been the only novelty of the last decades, allowing an increase in survival compared to standard chemotherapy (CT). However, IO is not approved for epithelioid histology in many countries. Therefore, therapy for relapsed MM remains an unmet clinical need, and the prognosis of MM remains poor, with an average survival of only 18 months. Increasing evidence reveals MM complexity and heterogeneity, of which histological classification fails to explain. Thus, scientific focus on possibly new molecular markers or cellular targets is increasing, together with the search for target therapies directed towards them. The molecular landscape of MM is characterized by inactivating tumor suppressor alterations, the most common of which is found in CDKN2A, BAP1, MTAP, and NF2. In addition, cellular targets such as mesothelin or metabolic enzymes such as ASS1 could be potentially amenable to specific therapies. This review examines the major targets and relative attempts of therapeutic approaches to provide an overview of the potential prospects for treating this rare neoplasm.
    Keywords:  mesothelioma; molecular alterations; targeted therapy
    DOI:  https://doi.org/10.3390/cancers16111971
  6. J Cancer Metastasis Treat. 2023 ;pii: 21. [Epub ahead of print]9
    The past, present, and future of targeted therapeutic approaches in patients with diffuse pleural mesotheliomas.
    Michael Offin, Bailey Fitzgerald, Marjorie G Zauderer, Deborah Doroshow.
      Despite our growing understanding of the genomic landscape of diffuse pleural mesotheliomas (DPM), there has been limited success in targeted therapeutic strategies for the disease. This review summarizes attempts to develop targeted therapies in DPM, focusing on the following targets being clinically explored in recent and ongoing clinical trials: vascular endothelial growth factor, mesothelin, BRCA1-associated protein 1, Wilms tumor 1 protein, NF2/YAP/TAZ, CDKN2, methylthioadenosine phosphorylase, v-domain Ig suppressor T-cell activation, and argininosuccinate synthetase 1. Although preclinical data for these targets are promising, few have efficaciously translated to benefit our patients. Future efforts should seek to expand the availability of preclinical models that faithfully recapitulate DPM biology, develop clinically relevant biomarkers, and refine patient selection criteria for clinical trials.
    Keywords:  Mesothelioma; biomarkers; genomics; targeted therapy
    DOI:  https://doi.org/10.20517/2394-4722.2022.140
  7. Br J Gen Pract. 2024 Jun 20. pii: bjgp24X737373. [Epub ahead of print]74(suppl 1):
    Rethinking continuity in primary care for people with mesothelioma.
    Emilie Couchman, Steph Ejegi-Memeh, Sarah Mitchell, Clare Gardiner.
       BACKGROUND: Mesothelioma is a terminal disease that is linked to asbestos exposure. Continuity is difficult for GPs, and other healthcare professionals (HCPs), to provide within the current NHS primary care system, but is highly valued by people with mesothelioma.
    AIM: To understand the experiences of continuity in primary care among people with mesothelioma, their close persons, and their HCPs; how they achieve this (or not); and how it affects their healthcare service use.
    METHOD: Realist case studies of patient journeys through the healthcare system (involving longitudinal interviews with people with mesothelioma, their close persons, and HCPs; and exploration of the organisational context). Data analysis allowed understanding of hidden mechanisms (resources and reasoning), triggered in certain contexts, leading to specific outcomes.
    RESULTS: Forty-eight interviews (involving 9 patients, 8 close persons, and 12 HCPs) were undertaken (totalling 30.8 hours/1848 minutes). Context-Mechanism-Outcome configurations related to: challenges unique to mesothelioma; capacity of patients/close persons/HCPs to facilitate continuity; multidisciplinary (MDT) approach differs from the family doctor model; and 'the NHS primary care system is broken'.
    CONCLUSION: Patients perceive their continuity needs to be unmet by the inflexible primary care system, which needs to adapt to a society in which people receive increasingly novel treatments and live longer with complex healthcare needs. A societal perspective shift is required to understand that an MDT now shares responsibility for care, rather than an individual family doctor. Policy documents continue to focus on access, and still do not advocate strongly enough for continuity, despite unequivocal evidence demonstrating its worth.
    DOI:  https://doi.org/10.3399/bjgp24X737373
  8. NPJ Precis Oncol. 2024 Jun 15. 8(1): 133
    NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity.
    Duo Xu, Shiyuan Yin, Yongqian Shu.
      Neurofibromatosis type 2 (NF2) is a tumor suppressor gene implicated in various tumors, including mesothelioma, schwannomas, and meningioma. As a member of the ezrin, radixin, and moesin (ERM) family of proteins, merlin, which is encoded by NF2, regulates diverse cellular events and signalling pathways, such as the Hippo, mTOR, RAS, and cGAS-STING pathways. However, the biological role of NF2 in tumorigenesis has not been fully elucidated. Furthermore, cross-cancer mutations may exert distinct biological effects on tumorigenesis and treatment response. In addition to the functional inactivation of NF2, the codeficiency of other genes, such as cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B), BRCA1-associated protein-1 (BAP1), and large tumor suppressor 2 (LATS2), results in unique tumor characteristics that should be considered in clinical treatment decisions. Notably, several recent studies have explored the metabolic and immunological features associated with NF2, offering potential insights into tumor biology and the development of innovative therapeutic strategies. In this review, we consolidate the current knowledge on NF2 and examine the potential connection between cancer metabolism and tumor immunity in merlin-deficient malignancies. This review may provide a deeper understanding of the biological roles of NF2 and guide possible therapeutic avenues.
    DOI:  https://doi.org/10.1038/s41698-024-00627-5
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