bims-mesote 2025-09-21 papers

Issue of 2025–09–21
five papers selected by
Laura Mannarino, Humanitas Research

J Thorac Dis. 2025 Aug 31. 17(8): 5687-5697

Inclusion of anti-vascular therapy as a promising option for later-line treatment of malignant pleural mesothelioma: a retrospective study.

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy with a poor prognosis. While pemetrexed-based chemotherapy and dual immunotherapy are established first-line treatments, optimal second- and later-line therapies remain underexplored. This study aims to evaluate later-line treatment options for MPM.
Methods: We retrospectively evaluated the outcomes of 85 patients with MPM who had failed in the first-line treatment between 2006 and 2023 in six hospitals. Survival outcomes were analyzed using Kaplan-Meier methodology, with between-group comparisons performed via log-rank testing. The Cox proportional hazards model was employed for both univariate and multivariate analyses to identify prognostic factors. Treatment response was assessed using standard efficacy endpoints: objective response rate (ORR) and disease control rate (DCR).
Results: This retrospective analysis evaluated 85 patients with advanced MPM. The cohort demonstrated a median progression-free survival (PFS) of 3.73 months and a median overall survival (OS) of 12.4 months. In the later-line, combining chemotherapy with anti-vascular therapy showed significant efficacy in median PFS than the chemotherapy scheme (4.57 vs. 3.00 months, P=0.004), as well as differences in median OS (13.00 vs. 10.03 months, P=0.04).
Conclusions: For patients with MPM requiring later-line treatment, the combination of chemotherapy and anti-vascular therapy may represent a viable therapeutic alternative, demonstrating an acceptable safety profile.

Keywords: Anti-vascular therapy; malignant pleural mesothelioma (MPM); pretreated patients

DOI: https://doi.org/10.21037/jtd-2025-566

Front Immunol. 2025 ;16 1578746

Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of diffuse pleural mesothelioma: a systematic review and meta-analysis.

Peiyuan Sun, Dandan Song, Ning Ma, Shufu Hou, Lei Liu, Jing Gao, Yanyan Tian.

Background: While clinical trials confirm the therapeutic value of PD-1/PD-L1 and CTLA-4 inhibitors in diffuse pleural mesothelioma, their real-world safety and efficacy profiles remain incompletely defined. This meta-analysis synthesizes clinical evidence to comprehensively evaluate these outcomes, addressing an urgent need for robust real-world evidence.
Methods: PubMed, Embase, the Cochrane Library were systematically searched for relevant studies. Outcomes including median progression-free survival (mPFS), median overall survival (mOS), 1-year overall survival (1-y OS), 1 year progression-free survival (1-year PFS),objective response rate (ORR), disease control rate (DCR), complete response(CR),partial response (PR), stable disease(SD), progressive disease(PD), treatment-related adverse events (TRAEs) and ≥grade 3 TRAEs were extracted for further analysis. The risk of bias was assessed by subgroup analysis.
Results: 14 articles with 1345 patients were identified and subjected to meta-analysis. With regard to survival analysis, the pooled mOS and mPFS were 6.66 months (95%CI 4.85-9.16) and 2.92 months (95%CI 2.23-3.83), respectively. In terms of tumor response, the pooled ORR and DCR were 21% (95%CI 6%-41%) and 49% (95%CI 27%-71%), respectively. The pooled AEs rate and ≥ grade 3 AEs rate were 94% (95%CI 86%-99%) and 44% (95%CI 30%-58%).
Conclusion: PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors have shown effective clinical responses in the treatment of Diffuse Pleural Mesothelioma (DPM). Although the incidence of adverse reactions is high, they are generally tolerable.
Systematic Review Registration: www.inplasy.com, identifier INPLASY202520045.

Keywords: CTLA-4; PD-1; PD-L1; immune checkpoint inhibitors; malignant pleural mesothelioma

DOI: https://doi.org/10.3389/fimmu.2025.1578746

Pathol Int. 2025 Sep 19.

Two Cases of Diffuse Pleural Mesothelioma Discovered After Spontaneous Pneumothorax.

Yuki Kato, Susumu Kirimura, Eisaku Ito, Ichiro Kasahara, Kenichi Ohashi.

Keywords: aged; mesothelioma; pleural neoplasms; pneumothorax; spontaneous; thoracic surgery

DOI: https://doi.org/10.1111/pin.70051

Radiology. 2025 Sep;316(3): e250531

Radiologist's Guide to the Ninth Edition TNM Staging System for Quantitative and Qualitative Assessment of Pleural Mesothelioma.

David J Murphy, Anna K Nowak, Thomas Frauenfelder, Michelle S Ginsberg, Hiroshi Kodama, Veronica Lenge de Rosen, Maria Mayoral, Christopher Straus, Giulia Benedetti, Valerie W Rusch, Ritu R Gill.

Pleural mesothelioma is a highly lethal, rare thoracic malignant neoplasm arising from mesothelial cells. Previous versions of the clinical TNM staging classification have relied on a qualitative radiologic assessment of tumor invasion. However, these qualitative assessments have not proved practical to implement, with poor interobserver agreement and lack of prognostic significance. The updated ninth edition of the International Association for the Study of Lung Cancer TNM staging system for pleural mesothelioma, jointly published by the American Joint Committee on Cancer and Union for International Cancer Control, proposes key evidence-based changes. The ninth edition incorporates quantitative measurements of pleural tumor and fissural thickness in the T descriptors for pleural mesothelioma and removes the qualitative descriptors that cannot be reliably detected on CT scans, such as endothoracic fascia, lung parenchymal invasion, and nontransmural diaphragm invasion or involvement. This article explains the rationale behind these changes and provides a practical guide to the ninth edition of the TNM staging system in clinical practice.

DOI: https://doi.org/10.1148/radiol.250531

Radiol Oncol. 2025 09 01. 59(3): 403-411

Genetic variability of HIF1A and response to treatment with cisplatin in combination with pemetrexed or gemcitabine in patients with malignant mesothelioma.

Matic Setina, Eva Setina, Ziga Doljak, Katja Goricar, Vita Dolzan, Viljem Kovac.

BACKGROUND: Treatment of malignant mesothelioma (MM) still relies on chemotherapy with cisplatin in combination with pemetrexed or other drugs. Studies indicate that hypoxic conditions within tumour tissue may reduce responsiveness to cisplatin-based chemotherapy. Hypoxia-inducible factors (HIF) play an important role in regulation of cellular adaptation to hypoxia. The aim of our study was to investigate single nucleotide polymorphisms (SNPs) in the HIF1A gene coding for the regulatory alpha subunit (HIF-1A) and their role in the response to chemotherapy in patients with MM.
PATIENTS AND METHODS: Our retrospective genetic association study included 234 patients with MM, who were treated with a combination of cisplatin/pemetrexed or cisplatin/gemcitabine at the Institute of Oncology Ljubljana between January 2001 and September 2018. Selected HIF1A SNPs (rs1154965, rs11549467, and rs2057482) were genotyped using the competitive allele-specific polymerase chain reaction (KASP). Additionally, we used a TaqMan assay for independent confirmation of rs11549465 genotyping results. The impact of the SNPs on response to chemotherapy was analysed using logistic regression. For survival analysis, we used the Kaplan-Meier method and Cox regression.
RESULTS: In heterozygotes with the HIF1A rs11549465 CT genotype, response to chemotherapy was significantly worse compared to homozygotes with the CC genotype, but only after adjustment for weight loss and CRP (ROadj = 0.37; 95% CI = 0.14-0.97; Padj = 0.044). HIF1A rs11549467 and rs2057482 were not associated with response to chemotherapy (all P > 0.05). None of the investigated SNPs were associated with progression-free survival or overall survival (all P > 0.05).
CONCLUSIONS: Among the investigated HIF1A SNPs, only rs11549465 has showed association with a worse response to chemotherapy after the adjustment for clinical parameters. The findings of this study have improved our understanding of the role of HIF1A polymorphisms in MM and may offer valuable insights into their impact on other cancers as well.

Keywords: chemotherapy; hypoxia-inducible factor; malignant mesothelioma; polymorphism

DOI: https://doi.org/10.2478/raon-2025-0049