bims-mesote 2025-02-16 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2025–02–16
eight papers selected by
Laura Mannarino, Humanitas Research

Malignant Pleural Mesothelioma: A 2025 Update.
"Current Status of Staging and Restaging Malignant Pleural Mesothelioma".
Diagnostic Challenges in the Pathological Approach to Pleural Mesothelioma.
Prevalence and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project.
Tumor Treating Fields enhance chemotherapy efficacy by increasing cellular drug uptake and retention in mesothelioma cells.
Malignant pleural mesothelioma.
Immune checkpoint inhibitors in the treatment of pleural mesothelioma: insights from real-world data.
Prognostic Stratification of Epithelioid Pleural Mesothelioma Based on the Hippo-TEADs Network.

J Clin Med. 2025 Feb 05. pii: 1004. [Epub ahead of print]14(3):

Malignant Pleural Mesothelioma: A 2025 Update.

Giuseppe Cardillo, David Waller, Sara Tenconi, Vincenzo Di Noia, Sara Ricciardi.

The incidence of pleural mesothelioma (PM) is slightly increasing, with 2417 new cases/year worldwide [...].

DOI: https://doi.org/10.3390/jcm14031004
Semin Nucl Med. 2025 Feb 10. pii: S0001-2998(25)00002-9. [Epub ahead of print]

"Current Status of Staging and Restaging Malignant Pleural Mesothelioma".

Egesta Lopci.

Malignant pleural mesothelioma (MPM) is the most frequent aggressive tumor affecting the pleura, accounting for over 38,000 deaths worldwide. It originates from the mesothelial cells and is mostly associated to asbestos exposure. Depending on the extent of the disease, the management of MPM varies from surgical intervention to a combination of systemic chemotherapy, immunotherapy, and radiation therapy. Major International scientific societies provide continuous updates on proper management of the disease, including recommendations on the optimal imaging algorithms, which are crucial for determining effective treatment options and optimizing clinical outcomes. However, despite the continuous efforts to improve patients' prognosis, median overall survival remains poor, ranging from 8 to 14 months. And even in case of initial response to treatment, local or distant recurrences represent almost a certainty, requiring appropriate imaging for the assessment of tumor sites. The aim of the present article is to illustrate the current status of imaging for staging and restaging of MPM, not forgetting most recent novelties in the diagnostic work-up of the disease.

DOI: https://doi.org/10.1053/j.semnuclmed.2025.01.003
Cancers (Basel). 2025 Feb 01. pii: 481. [Epub ahead of print]17(3):

Diagnostic Challenges in the Pathological Approach to Pleural Mesothelioma.

Stefano Lucà, Giovanna Pignata, Alessandro Cioce, Cecilia Salzillo, Rossella De Cecio, Gerardo Ferrara, Carminia Maria Della Corte, Floriana Morgillo, Alfonso Fiorelli, Marco Montella, Renato Franco.

  Malignant pleural mesothelioma (MPM) still represents a complex diagnostic challenge for pathologists in routine practice. This diagnosis requires a multidisciplinary approach, and pathological evaluation is mandatory. The histopathological diagnosis is stepwise and should be based on morphological and immunohistochemical assessment, sometimes associated with molecular tests, and supported by clinical and radiological findings. A correct morphological approach aims to exclude pleural metastasis or benign mesothelial proliferations, which are the main differential diagnoses. While certain histological features are diagnostic of MPM, others are highly suggestive but not definitive. Immunohistochemistry plays a pivotal role, with a panel of both traditional and newer markers being used to assess mesothelial differentiation and to differentiate malignant from benign proliferations. In more challenging cases, molecular tests, such as fluorescent in situ hybridization (FISH) to detect CDKN2A deletion, can be helpful in distinguishing malignant from benign pleural lesions. This review summarizes the key morphological, immunohistochemical, and molecular features that should be considered when pleural biopsy samples are examined, with the aim of improving diagnostic accuracy in this complex area.

Keywords:  histopathology; malignant; molecular tests; pleural mesothelioma

DOI:  https://doi.org/10.3390/cancers17030481
JCO Precis Oncol. 2025 Feb;9 e2400675

Prevalence and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project.

ETOP Mesoscape Consortium

PURPOSE: CD276 (B7-H3) is an immunoregulatory protein that plays an important role in the inhibition of T-cell function. CD276 is overexpressed on a variety of human solid cancer cells with limited expression in normal tissues, making it an appealing target for innovative cancer immunotherapy approaches. Pleural mesothelioma (PM) is a highly aggressive disease with a need for new treatment options. Our objective was to investigate the expression of CD276 in the multicenter PM cohort of the European Thoracic Oncology Platform Mesoscape project and correlate the results with annotated clinical data.
MATERIALS AND METHODS: Using tissue microarrays (TMAs), the expression of CD276, assessed using a semiquantitative aggregate H-score method on the membrane (and secondarily in the cytoplasm), was correlated with clinicopathologic characteristics and survival outcome.
RESULTS: CD276 immunohistochemistry results were available for 353 patients, with mostly epithelioid histology (71%). Membranous CD276 expression was present in 86%. High membranous CD276 expression (H-score ≥the median H-score of 120) was significantly more common in females (P = .0029; 71% v 47%) and in epithelioid histology (P < .001; 59% v 29%), whereas no significant association in clinical outcome (overall survival [OS]/progression-free survival) was found. Cross-validation of the TMA method using whole sections revealed a moderate agreement for membranous assessment (Cohen's kappa = 0.47) and a lower agreement for cytoplasm assessment (Cohen's kappa = 0.37). In an exploratory analysis, high cytoplasmic CD276 expression was associated with worse prognosis (OS, log-rank P = .043), but was not significant when adjusting for other clinical variables.
CONCLUSION: Although no prognostic value of CD276 expression was found, its high membranous expression (86%) in the PM samples of the study supports further research of its potential as a therapeutic target for this disease.

DOI: https://doi.org/10.1200/PO-24-00675
Am J Cancer Res. 2025 ;15(1): 271-285

Tumor Treating Fields enhance chemotherapy efficacy by increasing cellular drug uptake and retention in mesothelioma cells.

Rosy Amodeo, Lavinia Morosi, Marina Meroni, Ezia Bello, Sara Timo, Roberta Frapolli, Maurizio D'Incalci, Monica Lupi.

  Tumor Treating Fields (TTFields) applied with standard chemotherapy have been approved for the first-line treatment of unresectable pleural mesothelioma (PM), an aggressive malignancy with limited effective therapy options. In this study, we demonstrated that the simultaneous exposure to TTFields and doxorubicin or vinorelbine enhanced treatment efficacy in patient-derived PM cells by increasing intracellular drug concentrations. This was achieved by modulating several genes that encode transport proteins, such as the downregulation of P-glycoprotein (P-gp). Using specific, sensitive and quantitative analytical techniques, we observed a more than 70% increase in intracellular concentrations of doxorubicin and vinorelbine in samples treated with TTFields, and a greater than 50% increase in drug uptake in cells exposed to TTFields and pemetrexed. This result indicates that the increased drug concentration observed in TTFields treated cells is significant not only for drugs that are P-gp substrates but also suggests that TTFields could potentially affect other efflux pumps. However, the co-exposure to the drug and TTFields was critical to increasing intracellular drug levels, highlighting the necessity of concurrent use with drugs to enhance the antiproliferative effects of treatment. The in vitro findings were further corroborated by in vivo pharmacokinetic experiments in mice subcutaneously injected with epithelioid PM tumors. Indeed, a 30% increase in intratumor concentrations was observed when vinorelbine was administered with TTFields. Our findings suggest that TTFields could be a well-tolerated approach for enhancing intratumoral drug levels and potentially achieving a more significant therapeutic impact on PM treatment.

Keywords:  Pleural mesothelioma; Tumor Treating Fields (TTFields); cancer therapy; cellular drug uptake; combination treatment; pharmacokinetics

DOI:  https://doi.org/10.62347/ODWL5634
BMJ Case Rep. 2025 Feb 13. pii: e263562. [Epub ahead of print]18(2):

Malignant pleural mesothelioma.

Pragati Rao D, Sruthy Vijayan, Shashidhar S Vananjakar, Prasanna Kumar T.

  Malignant pleural mesothelioma is a rare and aggressive tumour of the pleura, commonly linked to asbestos exposure. However, its diagnosis is challenging, especially without known exposure. We present the case of a woman in her early 70s with no history of asbestos exposure, who presented with progressive breathlessness and left-sided chest pain. Radiological assessment revealed a large pleural effusion and nodular pleural thickening. Malignant pleural mesothelioma was confirmed through histopathological analysis of biopsies obtained via medical thoracoscopy. The patient was initiated on a palliative chemotherapy regimen, underwent talc slurry pleurodesis for recurrent effusion, and is currently under follow-up. This case emphasises the importance of a high index of suspicion for malignant pleural mesothelioma in patients with unexplained pleural effusion, even in the absence of typical risk factors, and the need for a timely diagnosis due to the disease's dismal prognosis.

Keywords:  Lung cancer (oncology); Respiratory medicine

DOI:  https://doi.org/10.1136/bcr-2024-263562
Int J Clin Oncol. 2025 Feb 12.

Immune checkpoint inhibitors in the treatment of pleural mesothelioma: insights from real-world data.

Masatoshi Kanayama, Takehiko Manabe, Katsuma Yoshimatsu, Rintaro Oyama, Hiroki Matsumiya, Masataka Mori, Masaru Takenaka, Koji Kuroda, Fumihiro Tanaka.

   BACKGROUND: Immune checkpoint inhibitors (ICIs) have recently emerged as a promising strategy for the treatment of pleural mesothelioma (PM).
METHODS: This retrospective study evaluated treatment efficacy and safety in Japanese patients with PM treated with nivolumab and ipilimumab (N + I group: 41 patients) as first-line therapy and nivolumab monotherapy (N group: 33 patients) as second- or later-line treatment.
RESULTS: The median overall survival (OS) and progression-free survival (PFS) were not reached and 10.4 months in the N + I group, and 8.6 months and 3.5 months in the N group, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 68.3% of the N + I group and 72.7% of the N group, with grade 3-4 TRAEs in 19.5% and 12.1% of patients, respectively. Patients with an ECOG PS 0-1 had significantly better OS and PFS in both treatment groups (p < 0.001). In the N + I group, OS was significantly better in patients with TRAEs (p = 0.020) and in those with the epithelioid subtype (p = 0.047), although PFS was not significantly different (p = 0.138 and p = 0.154, respectively). In the N group, both OS (p = 0.007) and PFS (p = 0.048) were significantly longer in patients with TRAEs.
CONCLUSION: This study provides valuable real-world clinical evidence of the efficacy and safety of nivolumab plus ipilimumab and nivolumab monotherapy in Japanese patients with PM. These results support the use of ICIs as a viable treatment option for advanced or relapsed disease.

Keywords:  Immune checkpoint inhibitor; Ipilimumab; Nivolumab; Pleural mesothelioma

DOI:  https://doi.org/10.1007/s10147-025-02706-4
Cancers (Basel). 2025 Jan 30. pii: 469. [Epub ahead of print]17(3):

Prognostic Stratification of Epithelioid Pleural Mesothelioma Based on the Hippo-TEADs Network.

Anello Marcello Poma, Rossella Bruno, Iacopo Petrini, Iosè Di Stefano, Alessandra Celi, Andrea Sbrana, Sabrina Cappelli, Antonio Chella, Franca Melfi, Marco Lucchi, Greta Alì.

  Background. The Hippo pathway is the most frequently altered signaling in pleural mesothelioma (PM). Epithelioid PM (ePM) is associated with better outcome than non-epithelioid subtypes, but its prognosis can be heterogeneous. Here, we tried to stratify ePM using the expression levels of the Hippo-TEAD network. Methods. Thirty patients with ePM were included in this study. Tumors were stratified using the expression levels of 74 genes belonging to the Hippo-TEAD network and using the non-negative matrix factorization algorithm. Results were validated using ePM cases from the TCGA cohort. Alterations associated with the molecular subgroups were investigated using mutation and copy number alteration data from TCGA. Results. Two groups of ePM (i.e., HP1 and HP2) were identified and validated using TCGA data. HP2 comprises about one-third of tumors. These tumors are frequently high-grade (73% vs. 35%), have higher levels of downstream Hippo effectors (i.e., YAP1, WWTR1 and TEADs), lower levels of VSIR-which encodes for VISTA-and poorer PFS and OS. HP2 tumors commonly harbor homodeletions in Hippo core suppressors (25% vs. 3%), while no specific gene mutation or copy number alterations of Hippo genes was associated with the two groups. Conclusions. ePM can be stratified in prognostic subtypes based on the expression levels of the Hippo-TEAD network. Higher levels of downstream Hippo effectors are associated with poor response to platinum-pemetrexed doublet and worse OS. The stratification of ePM based on the activation of the YAP/TAZ-TEAD axis is an intriguing approach in the light of the inhibitors of this signaling that are currently under investigation.

Keywords:  Hippo pathway; TAZ; TEADs; YAP1; pleural mesothelioma; prognosis

DOI:  https://doi.org/10.3390/cancers17030469