bims-mesote 2025-03-23 papers

Issue of 2025–03–23
six papers selected by
Laura Mannarino, Humanitas Research

J Clin Med. 2025 Feb 25. pii: 1547. [Epub ahead of print]14(5):

Prognostic Value of Chest CT Volumetric Analysis in Patients with Malignant Pleural Mesothelioma.

Elisa Baratella, Eleonora Ercolani, Antonio Segalotti, Marina Troian, Stefano Lovadina, Fabiola Giudici, Pierluca Minelli, Barbara Ruaro, Francesco Salton, Maria Assunta Cova.

Background/Objectives: Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer linked to asbestos exposure and with poor overall survival. In recent years, CT volumetric analysis has gained increasing interest as a more accurate method for assessing tumor burden. This study aims to evaluate the prognostic value of chest CT volumetric analysis in MPM, comparing tumor volume with tumor thickness measurements and survival outcomes. Methods: This is a retrospective, observational analysis of all patients undergoing diagnostic thoracoscopy between 2014 and 2021 at the University Hospital of Cattinara (Trieste, Italy). Inclusion criteria were as follows: age ≥ 18 years, histological diagnosis of MPM, and the availability of at least one contrast-enhanced chest CT scan at the time of diagnosis. For each patient, the tumor thickness was measured on the axial plane at three levels (upper, middle, and lower hemithorax). Tumor and effusion volumes were calculated with the RayStation® software version 11.7.174 (HealthMyne®, Madison, WI, USA). Results: A total of 81 patients were eligible for analysis. Maximum and mean tumor thickness were strongly associated with survival, with higher thicknesses correlating with an increased risk of death (adjusted hazard ratio per doubling (aHR) of 1.97 (95%CI: 1.40-2.77) and of 2.23 (95%CI: 1.56-3.20), p < 0.001)), respectively, while the effect of the tumor volume on survival was nevertheless significant but less impactful (aHR = 1.26 (1.10-1.45, p < 0.001)). The presence and volume of effusion did not correlate with survival (p = 0.48 and p = 0.64, respectively). Conclusions: This study supports the role of quantitative parameters for staging MPM, particularly given the frequent discrepancies between clinical and pathological staging when relying solely on qualitative measures.

Keywords: chest CT; mesothelioma; prognosis; volumetric analysis

DOI: https://doi.org/10.3390/jcm14051547

Cancer Control. 2025 Jan-Dec;32:32 10732748241301901

Malignant Pleural Mesothelioma CT Imaging: How to Measure It Correctly?

Carmine Picone, Annamaria Porto, Roberta Fusco, Vincenza Granata, Maria Chiara Brunese, Agnese Montanino, Giovanna Esposito, Raffaele Costanzo, Anna Manzo, Vincenzo Sforza, Claudia Sandomenico, Giuliano Palumbo, Edoardo Mercadante, Alessandro Ottaiano, Gianfranco Vallone, Ferdinando Caranci, Raffaella Mormile, Alessandro Morabito, Antonella Petrillo.

Background: Malignant pleural mesothelioma is the most common primary tumor of the pleura. The unique growth pattern of malignant pleural mesothelioma makes it difficult to apply the Response Evaluation Criteria for Solid Tumors (RECIST). Hence the need to use modified RECIST (mRECIST) criteria, as they better fit the unique growth pattern of malignant pleural mesothelioma. The thickness of the tumor perpendicular to the chest wall or mediastinum is measured at 2 points at 3 separate levels at least 1 cm apart on chest CT scans, and summed to obtain a one-dimensional pleural measurement. The same criterion has also been used to assess response to treatment. RECIST 1.1 represents a further update, taking into account new concepts such as revised minimum dimensions for lymph nodes and an approach to lesions that become non-measurable. Based on experience and published literature, the hypothesis of merging the 2 above-mentioned criteria in mRECIST 1.1 for mesothelioma and the use of iRECIST for the application to immune-based therapies (iRECIST) was considered. Purpose: Support the importance of studying pleural mesothelioma in a reliable and reproducible way, through a scrupulous methodology, applying the mRECIST1.1 and iRECIST criteria. Conclusions: Adoption of a standardized study metodology can make the study of PM reproducible and correct.

Keywords: RECIST criteria; computed tomography; malignant pleural mesothelioma

DOI: https://doi.org/10.1177/10732748241301901

Noncoding RNA Res. 2025 Jun;12 34-41

PD-L1 pfeRNAs as blood-based predictors of treatment response of unresectable malignant pleural mesothelioma patients administered Durvalumab with cisplatin and pemetrexed as first-line therapy.

Andrei Gurau, Suguru Yamauchi, Kaitlyn Ecoff, Kristen P Rodgers, James R Eshleman, Charles Conover Talbot Jr, Peng Huang, Joshua Choi, Patrick M Forde, Valsamo Anagnostou, Malcolm Brock, Yuping Mei.

Background: A new therapeutic avenue combining Durvalumab with cisplatin-pemetrexed (Durva-CP) has delivered a promising outcome for previously untreated patients with unresectable malignant pleural mesothelioma (MPM) in clinical trials. However, the limited patient response to Durva-CP needs predictors to select optimal candidates and monitor the developed resistance. Protein functional effector sncRNA (pfeRNA) reveals a fundamental mechanism underlying the regulation of protein activity. The common mechanisms underlying durvalumab, cisplatin, and pemetrexed indicate that PD-L1 pfeRNAs (PDLpfeRNAs) are key molecules that control the treatment response.
Methods: We specified PDLpfeRNAs by sncRNA deep sequencing, confirmed their binding to PD-L1 by immunoprecipitation and reverse pull-down assays, and demonstrated their roles in controlling the interaction behaviors of PD1/L1 through quality-controlled drug development assays. Following the standards required for the CLIA-compliant LDT, we measured their expression levels in 60 plasma biospecimens from 30 unresectable MPM patients enrolled in the PrE0505 Phase II multicenter study. Using the Cox proportional hazards model and Kaplan-Meier analyses, we described their significance in predicting the treatment response of unresectable MPM patients administered Durva-CP as first-line therapy.
Results: Two PDLpfeRNAs, PDLpfeRNAa and PDLpfeRNAb, were characterized, confirmed to bind to PD-L1, and identified to control the interaction behaviors of PD-1/L1. Their plasma relative expression levels (REL) demonstrated significant prognostic value for both overall survival (p = 0.0019) and progression-free survival (p = 0.019), and the association remained significant after adjusting for histological subtype (HR 2.59, 95 % CI: 1.00-6.70, p = 0.050) and age (HR 1.03, 95 % CI: 0.98-1.07, p = 0.269).
Conclusions: Plasma PDLpfeRNAs are predictors of treatment response of unresectable MPM patients treated with Durva-CP as first-line therapy to select optimal candidates and monitor the developed resistance.

Keywords: Cisplatin; Durvalumab; MPM; Non-invasive biomarker; PD-L1; Pemetrexed; pfeRNA

DOI: https://doi.org/10.1016/j.ncrna.2025.02.003

Ann Transl Med. 2025 Feb 28. 13(1): 8

A woman with a pleural mesothelioma and an inherited ATM mutation-a case report.

Marta Seca, B C John Cho, Angelina Tryon, Steven A Narod.

Background: Pleural mesothelioma (PM) is a rare and aggressive malignancy primarily linked to asbestos exposure. Up to 80% of patients have a history of such exposure. Several studies have investigated the possibility of a genetic predisposition for a subgroup of PM patients, but the data remains inconsistent. The ataxia-telangiectasia mutated (ATM) gene, crucial for DNA repair, is implicated in cancer susceptibility, with heterozygous mutations increasing risks, notably in breast and pancreatic cancers.
Case Description: We present a case of a 42-year-old woman, with no asbestos exposure history, diagnosed with metastatic PM. Initial treatment with immunotherapy showed limited efficacy. Given the rarity in young females, she opted for genetic testing via "The Screen Project", revealing a pathogenic ATM mutation. Due to enhanced radiosensitivity in ATM mutation carriers, to reduce adverse events conventional palliative radiotherapy (RT) was chosen over stereotactic hypofractionated RT. A follow-up computed tomography (CT) scan after 4 weeks indicated disease burden reduction.
Conclusions: This case highlights the importance of genetic testing in atypical PM cases, guiding treatment decisions tailored to individual genetic profiles. Awareness of ATM mutations can optimize therapeutic strategies, particularly regarding RT choices, in managing this challenging malignancy. Integrating genetic insights into clinical practice holds promise for enhancing treatment outcomes and refining management strategies in PM and related conditions.

Keywords: Ataxia-telangiectasia mutated mutation (ATM mutation); case report; pleural mesothelioma (PM); radiotherapy (RT)

DOI: https://doi.org/10.21037/atm-24-138

Ann Thorac Surg Short Rep. 2025 Mar;3(1): 222-224

Robotic Treatment of Postoperative Chylothorax.

Alfonso Fiorelli, Anna Cecilia Izzo, Vincenzo Di Filippo, Francesca Capasso, Domenico Galetta, Giovanni Natale.

A high-output chyle leak developed in a 69-year-old man who had undergone pleurectomy and decortication for malignant pleural mesothelioma. Conservative treatment was unsuccessful while a clear area of leakage could not be identified on lymphangiography. Right-sided robotic reexploration with ligation of the thoracic duct was successfully performed. The patient was discharged 6 days later, and no recurrence was observed.

DOI: https://doi.org/10.1016/j.atssr.2024.07.026

J Immunother Cancer. 2025 Mar 17. pii: e010112. [Epub ahead of print]13(3):

New soluble CSF-1R-dimeric mutein with enhanced trapping of both CSF-1 and IL-34 reduces suppressive tumor-associated macrophages in pleural mesothelioma.

Noémie Joalland, Agnès Quéméner, Sophie Deshayes, Romain Humeau, Mike Maillasson, Héloïse LeBihan, Apolline Salama, Judith Fresquet, Séverine Remy, Erwan Mortier, Christophe Blanquart, Carole Guillonneau, Ignacio Anegon.

BACKGROUND: Colony stimulating factor-1 receptor (CSF-1R) and its ligands CSF-1 and interleukin (IL)-34 have tumorigenic effects through both induction of suppressive macrophages, and survival/proliferation of tumor cells. In addition, the IL-34 tumorigenic effect can also be mediated by its other receptors, protein-tyrosine phosphatase zeta, Syndecan-1 (CD138) and triggering receptor expressed on myeloid cells 2. Small tyrosine kinase inhibitors are used to block CSF-1R signaling but lack specificity. Neutralizing anti-CSF-1 and/or IL-34 antibodies have been proposed, but their effects are limited. Thus, there is a need for a more specific and yet integrative approach.
METHODS: A human mutated form of the extracellular portion of CSF-1R was in silico modelized to trap both IL-34 and CSF-1 with higher affinity than the wild-type CSF-1R by replacing the methionine residue at position 149 with a Lysine (M149K). The extracellular portion of the mutated CSF-1R M149K was dimerized using the immunoglobulin Fc sequence of a silenced human IgG1 (sCSF-1RM149K-Fc). Signaling through CSF-1R, survival of monocytes and differentiation of suppressive macrophages were analyzed using pleural mesothelioma patient's samples and mesothelioma/macrophage spheroids in vitro and in vivo in the presence of sCSF-1RM149K-Fc or sCSF-1R-Fc wild type control (sCSF-1RWT-Fc).
RESULTS: We defined that the D1 to D5 domains of the extracellular portion of CSF-1R were required for efficient binding to IL-34 and CSF-1. The mutein sCSF-1RM149K-Fc trapped with higher affinity than sCSF-1RWT-Fc both CSF-1 and IL-34 added in culture and naturally produced in mesothelioma pleural effusions. sCSF-1RM149K-Fc inhibited CSF-1R signaling, survival and differentiation of human suppressive macrophage in vitro and in vivo induced by pleural mesothelioma cells. Neutralization of IL-34 and CSF-1 by sCSF-1RM149K-Fc also resulted in higher killing of pleural mesothelioma cells by a tumor-specific CD8+ T cell clone in mesothelioma/macrophage spheroids.
CONCLUSIONS: sCSF-1RM149K-Fc efficiently traps both CSF-1 and IL-34 and inhibits CSF-1R signaling, monocyte survival and suppressive macrophage differentiation induced by pleural mesothelioma cells producing CSF-1 and IL-34, as well as restores cytotoxic T-cell responses. sCSF-1RM149K-Fc has therapeutic potential vs other therapies under development targeting single components of this complex cytokine pathway involved in cancer.

Keywords: Cytokine; Immunotherapy; Macrophages; Mesothelioma; Tolerance

DOI: https://doi.org/10.1136/jitc-2024-010112