bims-mesote 2025-04-27 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2025–04–27
seven papers selected by
Laura Mannarino, Humanitas Research

The Role of Epithelial-Mesenchymal Transition in Malignant Pleural Mesothelioma: From Pathogenesis to Diagnosis and Treatment.
Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook.
Incidence and Outcomes of Brain Metastasis in Pleural Mesothelioma in the Era of Immunotherapy.
Efficacy and safety of bintrafusp alfa evaluated in a phase II single-arm clinical trial in previously treated advanced pleural mesothelioma.
Immunotherapy in mesothelioma - systematic review and meta-analysis of immunotherapy impact on OS and its correlation with PFS and ORR.
The percentage abundance of sarcomatoid component has a prognostic role in grade 4 non-metastatic clear cell-renal carcinoma.
Malignant Cell Count in Pleural Effusion: A Potential Indicator of Mortality.

Cells. 2025 Apr 12. pii: 585. [Epub ahead of print]14(8):

The Role of Epithelial-Mesenchymal Transition in Malignant Pleural Mesothelioma: From Pathogenesis to Diagnosis and Treatment.

Dimitrios E Magouliotis, Fabrizio Minervini, Ugo Cioffi, Matilde De Simone, Davide Patrini, Marco Scarci.

  Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural lining, primarily associated with asbestos exposure. Despite advancements in multimodal treatment, patient survival remains poor. Epithelial-mesenchymal transition (EMT) has emerged as a crucial process driving MPM pathogenesis, metastasis, and resistance to therapy. This review explores the molecular mechanisms underlying EMT in MPM, including key signaling pathways such as TGF-β, Wnt/β-catenin, and PI3K/Akt. We also discuss the diagnostic and prognostic significance of EMT-related biomarkers and emerging targeted therapies aimed at reversing EMT or exploiting EMT-induced vulnerabilities. Additionally, recent clinical trials, including the MARS 2 trial, are reviewed to provide insight into the evolving treatment landscape.

Keywords:  EMT; MPM; biomarkers; clinical trials; epithelial–mesenchymal transition; immunotherapy; malignant pleural mesothelioma

DOI:  https://doi.org/10.3390/cells14080585
Curr Treat Options Oncol. 2025 Apr 23.

Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook.

Giovanni Luca Ceresoli, Letizia Gianoncelli.

   OPINION STATEMENT: Pleural mesothelioma is an incurable cancer with unmet diagnostic and therapeutic needs. Due to its pattern of local spread, few patients are candidates for multimodality treatment and thus most patients only receive systemic therapy. Chemotherapy (pemetrexed plus platinum) was standard of care until the recent addition of immunotherapy (nivolumab plus ipilimumab, or pembrolizumab plus chemotherapy) as further first-line option. Physicians treating pleural mesothelioma should be aware of another option with Tumor Treating Fields (TTFields) therapy, a locoregionally-applied therapy utilizing electric fields generated by a portable medical device, and delivered to the tumor by skin-placed arrays. TTFields therapy delivered to the thorax using the NovoTTF- 100L device concomitant with pemetrexed and platinum agent is approved for unresectable pleural mesothelioma in the US, and received Conformité Européenne certification in Europe, based on results from the phase 2 STELLAR study (EF- 23; NCT02397928), where TTFields-related toxicity was limited to mild-to-moderate reversible skin reactions. Overall survival in the STELLAR study with TTFields therapy was 18.2 months, with further post-hoc analysis showing extended survival in patients with epithelioid histology. Within the evolving landscape of systemic treatments, TTFields therapy represents a novel and clinically versatile therapeutic option in the battle against pleural mesothelioma without introducing additional toxicities other than mild-to-moderate skin irritation. While promising, additional research is needed to optimize clinical application of TTFields therapy in patients with pleural mesothelioma, such as identifying the molecular determinants of therapy efficacy, and further investigation into the safe and effective delivery of TTFields therapy together with systemic agents, including immunotherapies.

Keywords:  Mechanism of action; Medical device usage; NovoTTF- 100L; NovoTTF- 200 T; Pleural mesothelioma; Tumor Treating Fields

DOI:  https://doi.org/10.1007/s11864-025-01320-w
JTO Clin Res Rep. 2025 May;6(5): 100823

Incidence and Outcomes of Brain Metastasis in Pleural Mesothelioma in the Era of Immunotherapy.

Margaret Stalker, Suzanne L Walker, Emily Lebow, Emily Ling-Lin Pai, Alex Watts, Wei-Ting Hwang, Amir Banihashemi, Evan Anderson, Leonid Roshkovan, Sharyn I Katz, Leslie Litzky, Andrew R Haas, Sunil Singhal, Corey J Langer, Keith Cengel, Melina E Marmarelis.

   Introduction: Immunotherapy (IO) has reported efficacy in pleural mesothelioma (PM). Brain metastases (BMs) in PM are rare; thus, surveillance brain imaging is not included in the guidelines. We evaluated the incidence of BM by treatment type.
Methods: In this retrospective analysis, patients with PM treated at the University of Pennsylvania between January 1, 2015, and August 31, 2023, were included. Demographic and clinical data were extracted from the medical records. The treatment categories included chemotherapy, single-agent IO, and dual-agent IO. A two-tailed Z score was used to determine a difference in the proportion of BM. Overall survival (OS) was analyzed using the Kaplan-Meier method. Of those with BM, available brain tissue was further analyzed.
Results: In total, 251 patients were included; the median age of the participants was 73 years (range: 35-92 y), 79% were male individuals, 91% were white, and 73% had epithelioid histology. In the study, 102 (40.6%) were treated with chemotherapy, 100 (39.8%) with single-agent IO, and 49 (19.5%) with dual-agent IO. The median OS (mOS) was 21.6 months (95% confidence interval: 17.7-25.5) and did not differ between treatment groups (p = 0.774). A higher proportion of patients treated with IO developed BM than those treated with chemotherapy (6/149 [4%] versus 0/102 [0%]; Z score p = 0.04). The mOS from BM diagnosis was 95 days (range: 16-1025 d). The histomorphology of three patients with available brain tissue were similar to the primary site and reported substantial edema and hemorrhage.
Conclusions: In this retrospective study, clinically significant BM was most prevalent in those exposed to IO and not seen in those receiving chemotherapy despite similar mOS between the groups. Brain imaging should be considered before starting IO in patients with PM.

Keywords:  Brain metastasis; Immunotherapy; Mesothelioma; Pleural mesothelioma; Survival

DOI:  https://doi.org/10.1016/j.jtocrr.2025.100823
Lung Cancer. 2025 Apr 17. pii: S0169-5002(25)00437-4. [Epub ahead of print]203 108545

Efficacy and safety of bintrafusp alfa evaluated in a phase II single-arm clinical trial in previously treated advanced pleural mesothelioma.

Spanish Lung Cancer Group

   OBJECTIVES: We aimed to evaluate the efficacy (progression-free survival [PFS]) of bintrafusp alfa in patients with pleural mesothelioma (PM) who had progressed to platinum-based chemotherapy and had not previously received immunotherapy. We also assessed overall survival [OS], objective response rate [ORR], and safety and tolerability.
MATERIALS AND METHODS: This open-label, non-randomised, multicentre, phase II, single-arm clinical trial was carried out by the Spanish Lung Cancer Group between October 2021 and March 2023 in 15 Spanish hospitals. We included patients ≥ 18 years old, with an ECOG PS of 0 or 1, with a histologically confirmed unresectable or metastatic PM, and with a life expectancy of at least three months.
RESULTS: 46 patients were included in the analysis. Most patients were men (78.3 %), the mean age was 70.0 years (SD, 9.5), and most presented epithelioid PM (84.8 %). The median PFS was 1.9 months (95 % CI, 1.7-3.2 months), the median duration of bintrafusp alfa response was 3.8 months, and the ORR was 6.5 % (95 % CI, 2.1-18.8 %). The median OS was 11.9 months (95 % CI, 5.8-15.7 months). Grade 3 or higher adverse events were observed in 34.8 % of patients and no grade 5 adverse event was reported.
CONCLUSION: Bintrafusp alfa did not reach the expected efficacy in patients with advanced PM. We did not identify new safety signals with bintrafusp alfa, and no case of bleeding was reported. Our study suggested that bintrafusp alfa has limited efficacy in PM, as reported in other solid tumours.

Keywords:  Immunotherapy; Mesothelioma; PD-L1; TGF-β blockade

DOI:  https://doi.org/10.1016/j.lungcan.2025.108545
J Chemother. 2025 Apr 22. 1-12

Immunotherapy in mesothelioma - systematic review and meta-analysis of immunotherapy impact on OS and its correlation with PFS and ORR.

Marko Skelin, Kaja Matić, Andrea Anić-Matić, Ivan Krečak, Bruna Perkov-Stipičin, Mirko Grubor.

  Mesothelioma has a poor prognosis, with a 5-year overall survival (OS) rate less than 5%. Immunotherapy has been proven as a promising alternative to platinum-based therapies in first-line treatment. Our systematic literature search included 7 randomized clinical trials involving 2,549 patients to evaluate the impact of immunotherapy on OS across different lines of therapy, histologic subtypes, and ECOG performance status, and to assess the correlation between OS, progression-free survival (PFS), and objective response rate (ORR). Immunotherapy significantly improved OS (HR 0.78, P = 0.0005) with a similar benefit observed in first-line and second/later-line treatment (P = 0.25) as well as in all ECOG statuses (P = 0.32). A significantly greater benefit was observed in non-epithelioid compared to epithelioid mesothelioma (P = 0.002). Additionally, a strong correlation was shown only between OS and PFS (r = 0.86, P = 0.01). Our results emphasize the importance of immunotherapy in mesothelioma and further support PFS as a surrogate endpoint.

Keywords:  Mesothelioma; chemotherapy; immunotherapy; objective response rate; overall survival; progression free survival

DOI:  https://doi.org/10.1080/1120009X.2025.2492935
World J Urol. 2025 Apr 23. 43(1): 243

The percentage abundance of sarcomatoid component has a prognostic role in grade 4 non-metastatic clear cell-renal carcinoma.

Giuseppe Lucarelli, Francesco Lasorsa, Monica Rutigliano, Martina Milella, Marco Spilotros, Antonio d'Amati, Giuseppe Ingravallo, Felice Crocetto, Savio Domenico Pandolfo, Marco Fabiano, Matteo Ferro, Riccardo Autorino, Michele Battaglia, Pasquale Ditonno.

   PURPOSE: Sarcomatoid dedifferentiation represents one of the most aggressive features of clear cell renal cell carcinoma (ccRCC). In this study we evaluated whether grade 4-ccRCC subclassification based on the intratumoral abundance of sarcomatoid features could have a prognostic impact.
METHODS: A cohort of 212 patients with localized or locally advanced sarcomatoid ccRCC was identified. This population was stratified according to abundance of sarcomatoid features in low-sarcomatoid (LS = < 20% sarcomatoid component; n = 117) and high-sarcomatoid (HS = ≥ 20% sarcomatoid component; n = 95). Estimates of cancer-specific survival (CSS) and recurrence-free survival (RFS) were calculated according to the Kaplan-Meier method and compared with the log-rank test. Multivariable analysis was performed using the Cox proportional hazards regression model to identify the most significant variables for predicting CSS and RFS.
RESULTS: Kaplan-Meier survival curves stratified by abundance of sarcomatoid component, showed that CSS and RFS were significantly decreased in patients with sarcomatoid component ≥ 20% (both P < 0.0001). At multivariable analysis by Cox regression modeling, the abundance of sarcomatoid component was an independent adverse prognostic factor for CSS (P < 0.0001) and RFS (P < 0.0001).
CONCLUSION: ccRCC Subclassification based on the abundance of intratumoral sarcomatoid component has a clinical significance. Our study showed that ccRCC subclassification into HS versus LS groups had a prognostic impact in terms of CSS and RFS in non-metastatic ccRCC.

Keywords:  Grading; Percentage; Prognosis; Renal cell carcinoma; Sarcomatoid

DOI:  https://doi.org/10.1007/s00345-025-05630-4
Am J Med Sci. 2025 Apr 17. pii: S0002-9629(25)00985-1. [Epub ahead of print]

Malignant Cell Count in Pleural Effusion: A Potential Indicator of Mortality.

Celal Satici, Sinem Nedime Sokucu, Ibrahim Aras, Furkan Atasever, Damla Azakli, Halide Nur Urer.

   BACKGROUND: The role of malignant cell count in pleural fluid as a potential predictor of survival remains under investigation. This study aims to assess the relationship between malignant cell count in pleural effusion and mortality in patients with malignant pleural effusion (MPE).
METHODS: This retrospective cohort study was conducted at a tertiary referral and research hospital, including treatment-naive patients diagnosed with MPE. Univariate and multivariate Cox regression analyses were employed to identify independent predictors of mortality.
RESULTS: A total of 63 patients were included in the analysis, with a male predominance (39 males, 61.9%) and a mean age of 65.7 ± 12.5 years. The majority (76.2%) of patients had NSCLC. Patients were stratified based on malignant cell count into two groups: those with <1700 cells/2mm² and those with ≥1700 cells/2mm². The two groups were similar in demographics, blood and pleural fluid parameters, and comorbidities. Multivariate Cox regression analysis revealed that male gender (HR: 4.14, 95% CI: 1.65-10.39), active smoking (HR: 2.99, 95% CI: 1.25-7.16), and malignant cell count (HR: 0.23, 95% CI: 0.09-0.56) were independent predictors of mortality.
CONCLUSION: Our findings indicate that a malignant cell count of <1700 cells/2mm², male gender and active smoking are independent prognostic factors associated with increased mortality in patients with MPE. Further large-scale prospective studies are necessary to confirm the clinical relevance of cytological malignant cell counts and to explore the viability and functional significance of these cells.

Keywords:  Malignant pleural effusion; malignant cell count; prognosis

DOI:  https://doi.org/10.1016/j.amjms.2025.04.003