bims-mesote 2022-03-06 papers

Issue of 2022–03–06
six papers selected by
Laura Mannarino, Humanitas Research

Front Bioeng Biotechnol. 2022 ;10 797900

ECM Mechanoregulation in Malignant Pleural Mesothelioma.

Valeria Panzetta, Ida Musella, Sabato Fusco, Paolo A Netti.

Malignant pleural mesothelioma is a relatively rare, but devastating tumor, because of the difficulties in providing early diagnosis and effective treatments with conventional chemo- and radiotherapies. Patients usually present pleural effusions that can be used for diagnostic purposes by cytological analysis. This effusion cytology may take weeks or months to establish and has a limited sensitivity (30%-60%). Then, it is becoming increasingly urgent to develop alternative investigative methods to support the diagnosis of mesothelioma at an early stage when this cancer can be treated successfully. To this purpose, mechanobiology provides novel perspectives into the study of tumor onset and progression and new diagnostic tools for the mechanical characterization of tumor tissues. Here, we report a mechanical and biophysical characterization of malignant pleural mesothelioma cells as additional support to the diagnosis of pleural effusions. In particular, we examined a normal mesothelial cell line (Met5A) and two epithelioid mesothelioma cell lines (REN and MPP89), investigating how malignant transformation can influence cellular function like proliferation, cell migration, and cell spreading area with respect to the normal ones. These alterations also correlated with variations in cytoskeletal mechanical properties that, in turn, were measured on substrates mimicking the stiffness of patho-physiological ECM.

Keywords: atomic force microscope; cell biophysical properties; malignant pleural mesothelioma; mechanical properties of tumor tissues; mechanobiology

DOI: https://doi.org/10.3389/fbioe.2022.797900

JTO Clin Res Rep. 2022 Mar;3(3): 100280

A Real-World Analysis of the Use of Systemic Therapy in Malignant Pleural Mesothelioma and the Differential Impacts on Overall Survival by Practice Pattern.

Kathleen Kerrigan, Yeonjung Jo, Jonathan Chipman, Benjamin Haaland, Sonam Puri, Wallace Akerley, Shiven Patel.

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive malignancy that affects older adults with frequent comorbidities, making real-world treatment decisions challenging. This study compares the overall survival (OS) of patients with MPM by physician's choice of first-line (1L) platinum chemotherapy (PC), second-line (2L) immunotherapy versus chemotherapy, and by receipt of maintenance therapy (MT).
Methods: The study included patients diagnosed with advanced MPM in the Flatiron Health electronic health record-derived database who initiated PC with pemetrexed in the 1L setting between 2011 and 2019. Patients in the 2L therapy analysis received single-agent chemotherapy versus immunotherapy after the progression of disease from our 1L cohort. Patients in the MT cohort were identified on the basis of continued receipt of pemetrexed with or without bevacizumab after dropping PC at prespecified intervals. The OS of patients by choice of 1L PC, 2L immunotherapy versus chemotherapy, and receipt of MT was summarized by means of Kaplan-Meier survival estimates and compared in the context of propensity score matching weighted analyses.
Results: In propensity score matching weighting analysis from 2065 patients with MPM, there was no evidence of an OS difference by choice of 1L PC (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 0.89-1.31, p = 0.43), suggestive evidence of an OS difference by choice of 2L immunotherapy versus chemotherapy (HR = 0.68, 95% CI: 0.42-1.08; p = 0.10), and no evidence of an OS difference by receipt of MT (HR = 0.92, 95% CI: 0.72-1.16, p = 0.46).
Conclusions: Using real-world, propensity score-matched weighted analysis of MPM, we found there was no difference in OS by choice of 1L PC, 2L immunotherapy or chemotherapy, or by receipt of MT.

Keywords: First-line platinum therapy; Maintenance therapy; Malignant pleural mesothelioma; Overall survival; Real-world outcomes; Second-line therapy

DOI: https://doi.org/10.1016/j.jtocrr.2022.100280

Front Oncol. 2022 ;12 823839

Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights.

Francesco Fortarezza, Federica Pezzuto, Andrea Marzullo, Domenica Cavone, Daniele Egidio Romano, Antonio d'Amati, Gabriella Serio, Luigi Vimercati.

Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.

Keywords: asbestos; malignant mesothelioma; molecular pathways; peritoneal mesothelioma; prognostic factors

DOI: https://doi.org/10.3389/fonc.2022.823839

Gen Thorac Cardiovasc Surg. 2022 Feb 28.

Control of air leakage during pleurectomy/decortication by the ventilation and anchoring method.

Masaki Hashimoto, Nobuyuki Kondo, Toru Nakamichi, Akifumi Nakamura, Ayumi Kuroda, Teruhisa Takuwa, Seiji Matsumoto, Seiki Hasegawa.

OBJECTIVES: We previously established a novel method of lung repair called the ventilation and anchoring (V/A) method. We evaluated the usefulness of the V/A method for controlling air leakage during pleurectomy/decortication (P/D).
METHODS: For this study, we enrolled patients with malignant pleural mesothelioma (MPM) who planned to receive P/D. Our lung repair method involves (1) suturing lung parenchyma for an apparent injured lesion and (2) coating the lung parenchyma with fibrin glue (FG) using the V/A method. The tidal volume (TV) was measured under pressure-controlled ventilation in the ipsilateral-affected lung 10 times at the following four points: after thoracotomy, at completion of visceral pleurectomy, after suturing lung parenchyma, and 5 min after coating with FG. The primary endpoint was the mean TV (mTV) change, and the secondary endpoints were the duration of air leakage and incidence of pleurodesis.
RESULTS: Between April 2014 and April 2016, 25 patients of the 29 consecutive patients enrolled were eligible. The mTV significantly decreased after completion of visceral pleurectomy but significantly increased after repair of the lung parenchyma, especially after coating with FG. The median duration of postoperative air leakage was 4 days (range: 2-19 days). Postoperative air leakage > 7 days was observed in 11 (44%) patients. Of these 11 patients, 6 received pleurodesis; however, no further revision was needed.
CONCLUSIONS: Significant increases in TV were observed after coating with FG via the V/A method during P/D. Coating with FG using the V/A method can contribute to a reduction in air leakage during P/D.

Keywords: Fibrin glue; Malignant pleural mesothelioma; Pleurectomy/decortication

DOI: https://doi.org/10.1007/s11748-022-01789-4

J Thorac Cardiovasc Surg. 2022 Jan 22. pii: S0022-5223(22)00090-3. [Epub ahead of print]

Checkpoint blockade in unresectable pleural mesothelioma: Event horizon for multimodal therapy.

R Taylor Ripley, Aaron S Mansfield, Boris Sepesi, Raphael Bueno, Bryan M Burt.

Keywords: checkpoint blockade; checkpoint inhibitor; immunotherapy; ipilimumab; mesothelioma; nivolumab; pleura

DOI: https://doi.org/10.1016/j.jtcvs.2022.01.020

J Thorac Cardiovasc Surg. 2022 Feb 09. pii: S0022-5223(22)00127-1. [Epub ahead of print]

Commentary: A chess game for mesothelioma treatment: Not checkmate yet!

Harvey I Pass.

DOI: https://doi.org/10.1016/j.jtcvs.2022.02.003