bims-mesote 2025-09-14 papers

Issue of 2025–09–14
five papers selected by
Laura Mannarino, Humanitas Research

Cancers (Basel). 2025 Aug 26. pii: 2786. [Epub ahead of print]17(17):

Malignant Local Seeding in Procedure Tracts of Pleural Mesothelioma: Incidence and Novel Risk Factors in 308 Patients.

Moshe Lapidot, Emanuele Mazzola, Raphael Bueno.

Background/Objectives: Unlike other thoracic malignancies, seeding malignant cells along surgical tracts is a known complication of invasive diagnostic or therapeutic procedures for pleural mesothelioma (PM). We report the tract dissemination rate and risk factors in 308 consecutive patients treated over 9 years in a single institution who underwent pleurectomy decortication (PD). Methods: Clinical and outcome data were reviewed. Fisher's exact test, Kaplan-Meier estimators, and log-rank tests were used to identify significant risk factors for surgical tract dissemination and to compare overall survival. Results: There were 233 males (75.6%), 187 right-sided operations (61%), 190 (61.7%) epithelioid histology cases, and the median age was 69 (29-84). During the study, malignant cell dissemination in resected surgical tracts was diagnosed in 69 (22.4%) patients. The dissemination rates in epithelioid, biphasic, and sarcomatoid tumors were 24.7%, 20.4%, and 0%, respectively. Disseminated malignant surgical tract was associated with advanced nodal status (p = 0.001), advanced staging by the American Joint Committee on Cancer (AJCC 8th edition, p = 0.03), female sex (0.02), side of surgery (p = 0.03), and the number of video-assisted thoracoscopic surgery (VATS) ports (p = 0.003). In epithelioid mesothelioma, the median survival from diagnosis was 19.7 months in patients with tract seeding versus 36.3 months in patients without seeding (hazard ratio, 1.9; p = 0.001). Conclusions: Procedure tract dissemination occurs in almost every fourth patient with pleural mesothelioma and is associated with shorter overall survival in the epithelioid subtype.

Keywords: pleural mesothelioma; pleurectomy decortication; procedure tracts; video-assisted thoracic surgery

DOI: https://doi.org/10.3390/cancers17172786

Transl Oncol. 2025 Sep 04. pii: S1936-5233(25)00251-7. [Epub ahead of print]61 102520

MiR-193b-3p and miR-132-3p as prognostic biomarkers of survival in pleural mesothelioma patients treated with first-line bevacizumab plus pemetrexed-platinum chemotherapy in the IFCT-0701 MAPS phase 3 trial.

Guénaëlle Levallet, Christian Creveuil, Alexandre Léger-Vigot, Solenn Brosseau, Claire Danel, Arnaud Scherpereel, Sylvie Lantuejoul, Julien Mazières, Laurent Greillier, Clarisse Audigier-Valette, Emmanuel Bergot, Denis Moro-Sibilot, Olivier Molinier, Hervé Léna, Isabelle Monnet, Franck Morin, Valérie Gounant, Gérard Zalcman.

We investigated whether angiogenesis-related microRNAs (miRNAs) predict survival in patients with pleural mesothelioma (PM) treated with bevacizumab plus pemetrexed-platinum chemotherapy in the Mesothelioma Avastin Cisplatin Pemetrexed Study ('MAPS', NCT00651456) phase 3 trial phase III trial (NCT00651456). Twelve miRNAs were measured in FFPE samples from 236 of the 448 MAPS trial patients (50.8 %), normalized to RNU48. Overall survival (OS) and progression-free survival (PFS) were analyzed by miRNA expression using univariate and multivariate models adjusted for clinical covariates. Internal validation was performed by bootstrapping. Interaction tests assessed the predictive value of each miRNA with respect to treatment arm. Low miR-193b-3p expression was associated with longer OS in PM patients, as shown in both univariate and multivariate analyses (adjusted HR = 0.87 [0.81-0.93], p < 0.001; bootstrap inclusion fraction [BIF]: 81.3 %), with both treatment arms analyzed together. It also predicted longer PFS (adjusted HR = 0.91 [0.85-0.97], p = 0.0042). Interaction tests revealed that for four miRNAs (miR-155-5p, miR-29c-5p, miR-132-3p, and miR-100-5p), lower expression levels were associated with greater efficacy of the bevacizumab/cisplatin/pemetrexed combination. Notably, the interaction between treatment arms and miR-132-3p expression was statistically significant (p = 0.004). In the IFCT-GFPC-0701 MAPS trial, low miR-193b-3p expression demonstrated significant independent prognostic value, being associated with longer OS and PFS. Additionally, low expression of miR-155-5p, miR-29c-5p, miR-132-3p, and miR-100-5p showed independent predictive value for improved survival in the bevacizumab plus chemotherapy arm. Thus, a simple qRT-PCR assay of these four miRNAs may help identifying PM patients most likely to benefit from bevacizumab.

Keywords: Bevacizumab; Pleural mesothelioma; Predictive biomarker; microRNA

DOI: https://doi.org/10.1016/j.tranon.2025.102520

J Clin Med. 2025 Aug 23. pii: 5964. [Epub ahead of print]14(17):

Pleurectomy/Decortication Versus Extrapleural Pneumonectomy in Pleural Mesothelioma: A Systematic Review and Meta-Analysis of Survival, Mortality, and Surgical Trends.

Margherita Brivio, Matteo Chiari, Claudia Bardoni, Antonio Mazzella, Monica Casiraghi, Lorenzo Spaggiari, Luca Bertolaccini.

Background: The optimal surgical approach for malignant pleural mesothelioma (PM) remains a topic of debate. While extrapleural pneumonectomy (EPP) offers radical resection, it is associated with significant morbidity. Pleurectomy/decortication (P/D) is less extensive but may offer comparable oncologic outcomes with reduced perioperative risk. This study aimed to conduct a comprehensive systematic review and meta-analysis to systematically evaluate and quantitatively compare survival outcomes, 30-day postoperative mortality, and baseline characteristics between patients undergoing P/D and EPP for PM. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. MEDLINE, Embase, and Scopus were searched up to May 2025. Studies comparing EPP and P/D in PM that reported on survival, mortality, or baseline demographics were included. Data from 24 retrospective studies were extracted. Pooled estimates were calculated using random-effects models. Meta-regression and subgroup analyses were performed by geographic region and publication year. Results: P/D was associated with a significantly improved overall survival compared to EPP in the primary analysis (mean difference = 7.01 months; 95% CI: 1.15-12.86; p = 0.018), with substantial heterogeneity (I2 = 98.5%). In a sensitivity analysis excluding one statistical outlier, the survival benefit remained significant (mean difference = 4.31 months; 95% CI: 1.69-6.93), and heterogeneity was markedly reduced. The 30-day mortality rate was also significantly lower for P/D (odds ratio = 0.34; 95% CI: 0.13-0.88; p = 0.027). Patients undergoing P/D were, on average, 3.78 years older than those undergoing EPP (p < 0.001), whereas no significant difference was observed in the sex distribution between groups. Subgroup analyses by region and publication year confirmed the robustness of the findings. Meta-regression did not reveal substantial modifiers of survival. Conclusions: P/D demonstrates superior overall survival and reduced perioperative mortality compared to EPP, without evidence of baseline demographic confounding. These findings, derived from retrospective comparative studies, support the preferential use of P/D in eligible patients, particularly in high-volume centers, given its favorable safety profile and superior median survival. However, the absence of randomized trials directly comparing P/D and EPP and the potential influence of patient selection warrant cautious interpretation, and surgical decisions should be tailored to individual patient factors within a multidisciplinary setting.

Keywords: extrapleural pneumonectomy; lung cancer; meta-analysis; pleural mesothelioma; pleurectomy/decortication; surgical outcomes; systematic review

DOI: https://doi.org/10.3390/jcm14175964

Cancers (Basel). 2025 Aug 27. pii: 2797. [Epub ahead of print]17(17):

Oligometastatic Mesothelioma Treated with Ablative Radiotherapy (OMAR): A Multicenter Study.

BACKGROUND/OBJECTIVES: This multicenter retrospective study aims to evaluate the role of Ablative Radiotherapy (RT) in patients with unresectable pleural mesothelioma (PM) who experienced radiological progression after at least one line of chemotherapy, with a maximum involvement of three pleural or extrapleural sites.
METHODS: Adult patients (≥18 years) with PM treated with stereotactic radiotherapy between 2011 and 2022, limited to a maximum of three pleural or extrapleural sites, were included in the analysis. Ablative RT was required to be administered with radical intent. Endpoints were time to further systemic therapy (TFST), local control (LC), progression-free survival (PFS), overall survival (OS), and acute and late radiotherapy-related toxicity.
RESULTS: A total of 56 patients were identified from six Italian and one Swiss radiotherapy center. Treatment was generally well tolerated. Ten patients experienced grade 1 or 2 acute toxicity, while four patients reported persistent chest pain, with one case reaching grade 3 as late toxicity. The median TFST was 18.6 months, with TFST rates of 61.7% and 46.4% at 12 and 24 months, respectively. The median OS was 37.63 months, with 1- and 2-year OS rates of 85.2% and 65.6%. Local control was favorable (79% at 1 year), but most patients experienced disease recurrence outside the SABR treatment volume. The median disease progression-free survival (DPFS) was 8.17 months, with 1- and 2-year DPFS rates of 36% and 19%, respectively. Smoking history correlated with OS and DPFS in univariate analysis, while statistical significance for OS was maintained in multivariate analysis. Additionally, nodal status and PTV volume were associated with OS.
CONCLUSION: SABR is a safe and effective approach for the treatment of oligorecurrent/oligoprogressive PM. The time to further systemic therapy was extended up to 18 months. At two years, 10% of patients remained disease-free, and more than half were alive at three years, suggesting a potentially indolent biological behavior in oligometastatic PM.

Keywords: oligometastases; oligorecurrence; pleural mesothelioma; stereotactic ablative radiation therapy

DOI: https://doi.org/10.3390/cancers17172797

Nat Med. 2025 Sep 08.

Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses.

Immune checkpoint blockade (ICB) is standard of care in advanced diffuse pleural mesothelioma (DPM), but its role in the perioperative management of DPM is unclear. In tandem, circulating tumor DNA (ctDNA) ultra-sensitive residual disease detection has shown promise in providing a molecular readout of ICB efficacy across resectable cancers. This phase 2 trial investigated neoadjuvant nivolumab and nivolumab/ipilimumab in resectable DPM along with tumor-informed liquid biopsy residual disease assessments. Patients with resectable epithelioid/biphasic DPM enrolled sequentially to nivolumab 240 mg every 2 weeks (q2w) for three cycles (Arm A, n = 16) or nivolumab 3 mg kg-1 q2w for three cycles plus ipilimumab 1 mg kg-1 on cycle 1 (Arm B, n = 14), followed by surgery, optional chemotherapy and/or radiotherapy, and nivolumab 480 mg q4w for 1 year. Co-primary endpoints included safety and feasibility; key exploratory endpoints included progression-free survival (PFS), overall survival (OS) and ctDNA analyses. The trial met its primary endpoints, and, in Arms A and B, 81.3% and 85.7% of patients proceeded to surgery, respectively. Treatment was safe, with a single dose-limiting toxicity in each arm. In Arm A, median PFS and OS were 9.6 months (95% confidence interval (CI): 2.5-27.7) and 19.3 months (95% CI: 14.9-34.7), respectively. In Arm B, median PFS and OS were 19.8 months (7.1-not reached) and 28.6 months (20.4-not reached), respectively. Persistent ctDNA was detected during neoadjuvant therapy in patients who did not undergo complete surgical resection due to disease progression (Fisher's exact test, P = 0.00013). Patients with detectable ctDNA on cycle 3 and pre-surgery had shorter PFS (log-rank test, P = 0.027 and P = 0.0059, respectively); this association was more pronounced when quantitative ctDNA changes were considered (log-rank test, P = 1.8 × 10-6). Our findings support the feasibility of neoadjuvant ICB and the clinical utility of ctDNA analyses to capture residual disease in resectable DPM. ClinicalTrials.gov identifier: NCT03918252 .

DOI: https://doi.org/10.1038/s41591-025-03958-3