bims-mesote 2024-08-18 papers

Issue of 2024–08–18
four papers selected by
Laura Mannarino, Humanitas Research

Eur J Nucl Med Mol Imaging. 2024 Aug 12.

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.

Solfrid Thunold, Eivor Hernes, Saima Farooqi, Åsa Kristina Öjlert, Roslyn J Francis, Anna K Nowak, Weronika Maria Szejniuk, Søren Steen Nielsen, Susana Cedres, Marc Simo Perdigo, Jens Benn Sørensen, Carin Meltzer, Lars Tore Gyland Mikalsen, Åslaug Helland, Eirik Malinen, Vilde Drageset Haakensen.

PURPOSE: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy.
METHODS: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response.
RESULTS: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5.
CONCLUSION: MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response.
STUDY REGISTRATION: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic.
CLINICALTRIALS: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

Keywords: Immunotherapy; MTV; Pleural mesothelioma; SUV; Telomerase vaccine; [18F]FDG PET

DOI: https://doi.org/10.1007/s00259-024-06853-0

Eur Radiol. 2024 Aug 15.

Are there features that can predict the unresectability of pleural mesothelioma?

Maria Mayoral, Jose Arimateia Batista Araujo-Filho, Kay See Tan, Eduardo Ortiz, Prasad S Adusumilli, Valerie Rusch, Marjorie Zauderer, Michelle S Ginsberg.

INTRODUCTION: The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM.
METHODS: Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling.
RESULTS: Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p = 0.005), neoadjuvant treatment (p = 0.001), clinical T-stage (p < 0.0001), all pleural thickness measurements (p < 0.05), pleural thickness pattern (p < 0.0001) and degree (p = 0.033), lung invasion (p = 0.004), extrapleural space obliteration (p < 0.0001), extension to subphrenic space (p = 0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p = 0.002) and mediastinal invasion (p < 0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC) > 0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC = 0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC = 0.879).
CONCLUSION: Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM.
CLINICAL RELEVANCE STATEMENT: A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments.
KEY POINTS: About half of pleural mesothelioma patients are reported to receive an incorrect disease stage preoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.

Keywords: Mesothelioma; Neoplasm staging; Thoracic wall; Tomography

DOI: https://doi.org/10.1007/s00330-024-10963-6

Int J Cancer. 2024 Aug 15.

Stemness and hybrid epithelial-mesenchymal profiles guide peritoneal dissemination of malignant mesothelioma and pseudomyxoma peritonei.

Nayana Lazzari, Giulia Rigotto, Barbara Montini, Paola Del Bianco, Elena Moretto, Federica Palladino, Rocco Cappellesso, Marco Tonello, Carola Cenzi, Antonio Scapinello, Maria Assunta Piano, Carlo Riccardo Rossi, Piero Dalerba, Pierluigi Pilati, Antonio Sommariva, Maria Luisa Calabrò.

Intrabdominal dissemination of malignant mesothelioma (MM) and pseudomyxoma peritonei (PMP) is poorly characterized with respect to the stemness window which malignant cells activate during their reshaping on the epithelial-mesenchymal (E/M) axis. To gain insights into stemness properties and their prognostic significance in these rarer forms of peritoneal metastases (PM), primary tumor cultures from 55 patients selected for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were analyzed for cancer stem cells (CSC) by aldehyde dehydrogenase 1 (ALDH1) and spheroid formation assays, and for expression of a set of plasticity-related genes to measure E/M transition (EMT) score. Intratumor heterogeneity was also analyzed. Samples from PM of colorectal cancer were included for comparison. Molecular data were confirmed using principal component and cluster analyses. Associations with survival were evaluated using Kaplan-Meier and Cox regression models. The activity of acetylsalicylic acid (ASA), a stemness modifier, was tested in five cultures. Significantly increased amounts of ALDH1bright-cells identified high-grade PMP, and discriminated solid masses from ascitic/mucin-embedded tumor cells in both forms of PM. Epithelial/early hybrid EMT scores and an early hybrid expression pattern correlated with pluripotency factors were significantly associated with early peritoneal progression (p = .0343 and p = .0339, respectively, log-rank test) in multivariable models. ASA impaired spheroid formation and increased cisplatin sensitivity in all five cultures. These data suggest that CSC subpopulations and hybrid E/M states may guide peritoneal spread of MM and PMP. Stemness could be exploited as targetable vulnerability to increase chemosensitivity and improve patient outcomes. Additional research is needed to confirm these preliminary data.

Keywords: CRS‐HIPEC; cancer stem cells; epithelial‐mesenchymal plasticity; malignant mesothelioma; pseudomyxoma peritonei

DOI: https://doi.org/10.1002/ijc.35137

J Thorac Dis. 2024 Jul 30. 16(7): 4764-4771

Pleural fluid biomarkers: a narrative review.

Christopher Chan, Ken Ka Pang Chan.

Background and Objective: Pleural fluid is a source from which various biomarkers can be obtained and measured to facilitate the management and prognostication of various conditions. This narrative review aims to summarise a few selected applications of pleural fluid biomarker analysis based on the latest literature.
Methods: A literature search for articles published in English regarding human subjects from the period January 2000 to December 2023 was performed through PubMed. Publications considered by the authors to be relevant were included in this review, with additional references added based on the authors' judgement. This review considered both prospective and retrospective cohort studies analysing the clinical value of a range of pleural fluid biomarkers.
Key Content and Findings: The biomarkers selected in this narrative review have either established clinical applicability or promising initial results which require further research. Pleural fluid adenosine deaminase, mesothelin and N-terminal pro-B-type natriuretic peptide can optimize the diagnosis of tuberculous pleuritis, malignant mesothelioma and heart failure-related pleural effusion respectively. The detection rate for epidermal growth factor receptor mutations for lung cancer is higher in the pleural fluid than in the pleural tissue or plasma. Suitable targeted therapy in patients with detectable mutations can offer survival benefits. The pleural fluid neutrophil-lymphocyte ratio, soluble urokinase plasminogen activator receptor and plasminogen activator inhibitor 1 carry prognostic implications and can potentially guide subsequent treatment decisions. These biomarkers used individually, or in conjunction with other clinical parameters, should only be utilised in pre-defined, appropriate clinical conditions to maximize their clinical value.
Conclusions: A great variety of different biomarkers are available for analysis in pleural fluid. Further research and development are necessary to widen the spectrum and enhance the clinical utility of pleural fluid biomarkers. Comparison with the diagnostic utilities of serum biomarkers and other investigation parameters, such as radiological findings, could be considered when evaluating the performance of pleural fluid biomarkers.

Keywords: Pleural effusion; biomarkers; heart failure; malignant pleural effusion (MPE); pleural infection; tuberculous pleuritis

DOI: https://doi.org/10.21037/jtd-24-467