bims-mesote Biomed News
on Mesothelioma
Issue of 2024–10–20
eleven papers selected by
Laura Mannarino, Humanitas Research



  1. J Clin Med. 2024 Sep 30. pii: 5837. [Epub ahead of print]13(19):
      Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body's external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant mesothelioma, characterized by recurrent inflammation, disruption of cell division, activation of proto-oncogenes, and generation of free radicals. In pleural mesothelioma, BAP1, CDKN2A, and NF are the most often mutated genes. Accurate diagnosis and assessment usually require the use of chest computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.
    Keywords:  asbestos; biomarkers; chemotherapy; malignant pleural mesothelioma; mesothelioma; radiotherapy; surgery
    DOI:  https://doi.org/10.3390/jcm13195837
  2. Am J Respir Crit Care Med. 2024 Oct 15.
      
    Keywords:  Electrocautery Snare; Semirigid thoracoscopy; pleural biopsy; pleural effusion
    DOI:  https://doi.org/10.1164/rccm.202403-0619IM
  3. J Thorac Cardiovasc Surg. 2024 Oct 10. pii: S0022-5223(24)00914-0. [Epub ahead of print]
       OBJECTIVE: Immune checkpoint therapy (ICT) has significantly impacted malignant pleural mesothelioma (MPM) treatment. Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT.
    METHODS: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of MSLN and PD-L1. Both univariable and multivariable Cox regression analyses were used to determine independent prognosticators for overall survival (OS). A prospective ICT clinical trial and our historical cohort were included for validation.
    RESULTS: Seventy-seven patients (62%) were treated with either anti-PD-(L)1 monotherapy, and the remaining 38% were given combination ICT. Higher pre-ICT SMRP levels were observed in epithelioid versus non-epithelioid MPM. Serum PD-L1 levels did not show significant differences between the groups. Univariable analysis identified durable clinical benefit, development of immune-related adverse events, and SMRP levels as significantly associated with OS. Multivariable analysis confirmed SMRP as an independent prognostic factor, with lower levels (≤1.35 nmol/L) correlating with improved OS. The association of high SMRP with worse prognosis was validated in the prospective ICT clinical trial cohort and not in our historical cohort treated without ICT.
    CONCLUSIONS: SMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.
    Keywords:  SMRP; checkpoint immunotherapy; liquid biomarker; mesothelioma; prognostic biomarker; soluble PD-L1
    DOI:  https://doi.org/10.1016/j.jtcvs.2024.10.005
  4. J Community Hosp Intern Med Perspect. 2024 ;14(5): 14-20
       Background: Malignant Pleural Mesothelioma (MPM) is a primary pleural tumor with scarce prognostic data estimates given its rarity. This study aims to explore the epidemiologic and survival predictors amongst patients with MPM, extending from the largest and most recent study conducted between 1973 and 2009.
    Methods: 3384 patients diagnosed with MPM between 2010 and 2017 were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Demographics, clinical characteristics, overall mortality (OM), and cancer-specific mortality (CSM) estimates were analyzed. Multivariate Cox model was used to identify independent prognostic factors, where a hazard ratio (HR) greater than 1 denotes adverse prognostic factors.
    Results: Our cohort revealed a male predominance (77.16%), with over 80% diagnosed after age 59, peaking between 60 and 79 years old (60.17%). Epithelioid mesothelioma (41.78%), non-Hispanic whites (78.13%), and diagnosis at distant stage (71.60%) were the most common subgroups in their respective categories. 365 patients (10.79%) lacked pleural effusion at diagnosis. In multivariate analyses, higher overall mortality (OM) was associated with male gender (HR = 1.24, 95% CI 1.14-1.37, p < 0.01), age >80 years (HR = 2.17, 95% CI 1.41-3.35, p < 0.01), fibrous mesothelioma (HR = 2.21, 95% CI 1.95-2.51, p < 0.01), and distant stage (HR = 1.55, 95% CI 1.34-1.81, p < 0.01). Higher cancer-specific mortality (CSM) was associated with male gender (HR = 1.25, 95% CI 1.13-1.38, p < 0.01), age >80 years (HR = 2.02, 95% CI 1.29-3.15, p < 0.01), fibrous mesothelioma (HR = 2.24, 95% CI 1.97-2.55, p < 0.01), and distant stage (HR = 1.59, 95% CI 1.36-1.87, p < 0.01). Lower OM and CSM was observed in patients who underwent any type of treatment. Nonmalignant pleural effusion, based on histology, was associated with higher CSM (HR = 1.22, 95% CI 1.05-1.4, p < 0.05).
    Conclusion: Fibrous mesothelioma, older age, and distant disease were associated with increased mortality. All intervention strategies were associated with improved survival outcomes. Earlier diagnosis may improve outcomes, as available interventions are associated with lower mortality when feasible at diagnosis. The study paves the way for further prospective and retrospective studies to focus on the identification of patient subsets that may benefit from early mesothelioma screening.
    Keywords:  Malignant pleural mesothelioma; Rare malignancies; Rare oncology; Tumor epidemiology; Uncommon cancers
    DOI:  https://doi.org/10.55729/2000-9666.1384
  5. Int J Mol Sci. 2024 Oct 09. pii: 10861. [Epub ahead of print]25(19):
      Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%. Outcomes may vary according to stage at time of diagnosis and histologic subtype. Most recently, clinical trials utilizing dual checkpoint inhibitor regimens and chemotherapy in combination with immune oncologic agents have demonstrated impactful changes in outcomes. In this article, we review studies that have led to the successful implementation of immunotherapy in clinical practice for the treatment of this disease and highlight ongoing clinical trials exploring the use of different immunotherapy strategies for the treatment of pleural mesothelioma. We also discuss the challenges of immunotherapy-based approaches in the context of mesothelioma and future strategies currently being investigated to overcome them.
    Keywords:  immune checkpoint inhibitor; immunotherapy; mesothelioma
    DOI:  https://doi.org/10.3390/ijms251910861
  6. Cancers (Basel). 2024 Oct 08. pii: 3418. [Epub ahead of print]16(19):
      Background: Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth. Methods: The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters. Results: A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (p = 0.016). The presence of PD-L1 expression had a negative effect on overall survival (p = 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (p = 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis. Conclusions: Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.
    Keywords:  PD-L1; epithelioid; immune cell; pleural mesothelioma; sarcomatoid; t cell; thoracic cancer; tumor microenvironment
    DOI:  https://doi.org/10.3390/cancers16193418
  7. Clin Lung Cancer. 2024 Sep 21. pii: S1525-7304(24)00200-6. [Epub ahead of print]
       BACKGROUND: The phase 3 CheckMate-743 trial demonstrated a prolonged overall survival (OS) benefit with nivolumab plus ipilimumab over chemotherapy as first-line treatment in patients with unresectable pleural mesothelioma (PM). However, given that Latin American (LATAM) patients were notably underrepresented in this trial, we retrospectively assessed the effectiveness and safety of this regimen in this population.
    METHODS: This retrospective study included patients from 15 centers in LATAM with unresectable or metastatic PM treated with first-line nivolumab plus ipilimumab in a real-world data (RWD) scenario. Demographic, clinicopathological characteristics, and safety data were collected from medical charts. Progression-free survival (PFS), and OS were calculated using the Kaplan-Meier method.
    RESULTS: From June 2017, and January 2024 96 patients were included: epithelioid 78% (n = 75), 81% were ECOG 0-1 (n = 78). With a median follow-up of 24.1 months, median PFS and OS were 8 months (95% CI, 6.6-9.4), and 22 months (95% CI, 18.9-25), respectively. No statistical difference in OS was observed between epithelioid versus nonepithelioid histology (median 23 months vs. 19 months, respectively; P = .29). Treatment efficacy was also consistent among different clinical subgroups. Any and grade 3-4 adverse events were found in 43.1% (n = 28), and 18.5% (n = 12) of patients, respectively. Remarkably, no OS impact was observed in patients who had dose delay or treatment discontinuation due to immune-related adverse events, and those who experienced any adverse event.
    CONCLUSIONS: This multicenter RWD study demonstrated the clinically meaningful benefit of first-line ipilimumab and nivolumab in LATAM patients with unresectable or metastatic PM, and data is consistent with previous trial findings.
    Keywords:  Checkpoint inhibition; Immunotherapy; Malignant pleural mesothelioma; Nivolumab+Ipilimumab; Real-world
    DOI:  https://doi.org/10.1016/j.cllc.2024.09.005
  8. J Natl Compr Canc Netw. 2024 Oct;pii: e247031. [Epub ahead of print]22(8):
      Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma. At present, the recommended first-line systemic treatment options may include immunotherapy with nivolumab plus ipilimumab or chemotherapy with pemetrexed plus either cisplatin or carboplatin. For second-line treatment, the other previously unchosen first-line option can be used. Off-label bevacizumab may be considered in combination with chemotherapy among carefully selected patients. The benefit of third-line treatment or beyond is less clear. Nonetheless, a number of single-agent regimens show modest activity. Anecdotal reports of children or young adults with peritoneal mesothelioma harboring ALK rearrangement have suggested the efficacy of ALK inhibitors for this rare population. In summary, there is a growing number of systemic therapy options for peritoneal mesothelioma. To gain a better insight into this disease, future prospective trials in mesothelioma should include more patients with peritoneal mesothelioma.
    DOI:  https://doi.org/10.6004/jnccn.2024.7031
  9. Cancers (Basel). 2024 Oct 04. pii: 3391. [Epub ahead of print]16(19):
      Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction. The experimental pre-clinical background and rationale are discussed as well.
    Keywords:  cell therapy; local delivery; phase I study; pleural mesothelioma
    DOI:  https://doi.org/10.3390/cancers16193391
  10. Curr Opin Pulm Med. 2024 Oct 17.
       PURPOSE OF REVIEW: Translational research in Interventional Pulmonology has made significant advances in recent years, ranging from novel biomarkers and imaging to practice-changing clinical trials in lung cancer and pleural disease. This review article aims to summarize key research studies in the field to understand the latest published evidence and to highlight areas of growing academic interest.
    RECENT FINDINGS: In lung cancer, the role of novel imaging and biomarkers and their potential utility in early lung cancer diagnosis will be highlighted. In pleural disease, less invasive/conservative treatment in pneumothorax, early aggressive treatment in pleural infection along with novel biomarkers, and the shift beyond drainage strategies in malignant pleural effusion and mesothelioma will be discussed.
    SUMMARY: This overview of translational research in the field of interventional pulmonology will ultimately help to highlight the gaps in current evidence to promote research in areas of clinical significance.
    DOI:  https://doi.org/10.1097/MCP.0000000000001125
  11. Pathol Res Pract. 2024 Oct 15. pii: S0344-0338(24)00572-7. [Epub ahead of print]263 155661
       INTRODUCTION: High endothelial venules (HEVs) are vessels specialized in the extravasation of lymphocytes from the blood to the tissue implicated in the immune microenvironment of several tumors. Their presence has been never studied in the pleural tissue.
    MATERIAL AND METHODS: We retrospectively studied 149 surgical pleural biopsies by immunohistochemistry for MECA-79 expression, a marker specifically recognizing HEVs. The tissues included 44 (44 %) inflammatory and 105 (56 %) neoplastic diseases. The latter corresponded to 34 (22.8 %) mesotheliomas and 71 (47.7 %) metastases from lung (n=50) or breast (n=21) primaries.
    RESULTS: HEVs were present in 102 (68 %) of all pleural specimens with a mean number of foci containing HEVs of 13.33 (±20.64). Neoplastic pleural pathologies harbored HEVs in 73.3 % of the cases compared to the non-neoplastic pathologies which harbored HEVs in 56.8 % of the cases (p=0.048). Their presence did not differ between pulmonary or mammary metastasis (p=0.7).
    CONCLUSION: We show for the first time that HEVs are present in the pleural cavity probably participating in the immune microenvironment of inflammatory and neoplastic pleural disease.
    Keywords:  Inflammation; Lymphocyte recruitment; MECA-79; Mesothelium; Vessels
    DOI:  https://doi.org/10.1016/j.prp.2024.155661