bims-mesote 2021-11-21 papers

Issue of 2021–11–21
seven papers selected by
Laura Mannarino, Humanitas Research

J Thorac Dis. 2021 Oct;13(10): 5741-5751

BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma.

Albero Murrone, Luca Cantini, Federica Pecci, Valeria Cognigni, Cecilia Copparoni, Silvia Rinaldi, Ilaria Fiordoliva, Federica Monaco, Corrado Rubini, Francesca Barbisan, Alessia Cimadamore, Riccardo Giampieri, Francesca Bianchi, Marco Tomasetti, Monica Amati, Lory Santarelli, Rossana Berardi.

Background: Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM.
Methods: The expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival.
Results: In the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 vs. 17.0 months, P=0.017 and median PFS 8.7 vs. 5.1 months, P=0.020). The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients.
Conclusions: In this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.

Keywords: BRCA-associated protein 1 (BAP1); Malignant mesothelioma; miR-31; microRNA; prognosis

DOI: https://doi.org/10.21037/jtd-21-555

Eur Respir Rev. 2021 Dec 31. pii: 210057. [Epub ahead of print]30(162):

Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis.

Eline Schillebeeckx, Jan P van Meerbeeck, Kevin Lamote.

Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on invasive techniques, which are not well tolerated. Non-invasive diagnostic biomarkers have shown potential and could have a huge clinical benefit. However, despite extensive research, there is no consensus yet on their clinical use, with many articles reporting contradicting results, limiting their clinical implementation. The aim of this systematic review is therefore to explore the different semi- and non-invasive diagnostic markers in several human matrices and identify those that might clinically be relevant. A total of 100 articles were selected through Web of Science and PubMed, with 56 articles included in the quantitative analysis. Although many studies have reported on the diagnostic accuracy of MPM biomarkers such as serum mesothelin and high-mobility group box protein 1 and plasma fibulin-3, none have resulted in a validated test for early detection. Future research should focus on external validation, combinations into biomarker panels, the inclusion of early stage MPM patients and a combination of different biomarker matrices, as well as new markers.

DOI: https://doi.org/10.1183/16000617.0057-2021

Interact Cardiovasc Thorac Surg. 2021 Nov 18. pii: ivab307. [Epub ahead of print]

Localized malignant pleural mesothelioma of the interlobar fissure mimicking a lung cancer.

Paola Ciriaco, Stefano Viscardi, Federica Filipello, Giampiero Negri.

We report a case of localized malignant pleural mesothelioma (LMPM) of the interlobar fissure mimicking lung cancer. A 74-year-old woman presented with dyspnoea and a left pleural effusion. Chest computed tomography revealed a bulky mass, arising from the left lower lobe with intense uptake at the 18F-FDG PET. A left lower lobectomy was performed after thoracoscopic pleural biopsies. The final histology revealed an LMPM epithelioid like. We describe the diagnostic and curative path of the disease, speculating on the differential diagnosis and treatment of LMPM.

Keywords: Epithelioid like; Lung cancer; Mesothelioma

DOI: https://doi.org/10.1093/icvts/ivab307

BMC Pulm Med. 2021 Nov 15. 21(1): 373

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma.

Hiroto Yoneda, Hiroshi Nokihara, Atsushi Mitsuhashi, Ryohiko Ozaki, Yohei Yabuki, Hirokazu Ogino, Kenji Otsuka, Yasuhiko Nishioka.

BACKGROUND: Nivolumab is used for the treatment of malignant pleural mesothelioma (MPM). However, immune-related adverse events (irAEs) occur in patients treated with nivolumab. Several studies have reported the correlation between irAEs and therapeutic effects of immune checkpoint inhibitor, but none have reported the correlation in MPM. Here we report a retrospective study which shows the correlation between irAEs and therapeutic effects of nivolumab in patients with MPM.
METHODS: This study included patients treated with nivolumab at Tokushima University Hospital from February 2009 to September 2021. We retrospectively reviewed the medical records to evaluate the several clinical factors, such as the presence or absence of irAEs, their severities, progression-free survival (PFS), overall survival (OS) or objective response to the treatment.
RESULTS: Eleven patients received treatment with nivolumab. Objective response rate was 18.2% and the disease control rate was 90.9%. Median PFS was 6.8 months (95% confidence interval, 1.3 to 11.9 months) and median OS was 15.2 months (95% confidence interval, 8.9 to 21.5 months). IrAEs occurred in eight patients (72.7%), and grade ≥ 2 irAEs occurred in six patients (54.5%). PFS and OS were significantly longer in the grade ≥ 2 irAEs group than in grade < 2 irAEs group (median PFS 13.6 vs. 3.8 months, p = 0.0093; median OS not reached vs. 8.6 months, p = 0.0108).
CONCLUSIONS: This is the first study to report the correlation between irAEs and therapeutic effects in patients with MPM. Because the presence of irAEs may be associated with a favorable clinical outcome, early detection and appropriate management of irAEs will increase the therapeutic benefits to patients.

Keywords: Immune-related adverse events; Malignant pleural mesothelioma; Nivolumab; Therapeutic effect

DOI: https://doi.org/10.1186/s12890-021-01746-6

BMC Cancer. 2021 Nov 17. 21(1): 1235

A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma.

Zhongjian Chen, Chenxi Yang, Zhenying Guo, Siyu Song, Yun Gao, Ding Wang, Weimin Mao, Junping Liu.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research.
METHODS: A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets.
RESULTS: After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism.
CONCLUSIONS: To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.

Keywords: GC-MS; Malignant pleural mesothelioma; Metabolomics; Patient-derived xenograft; Ultrasound-guided biopsy

DOI: https://doi.org/10.1186/s12885-021-08980-5

Thorac Cancer. 2021 Nov 20.

Non-incisional pleurectomy/decortication for malignant mesothelioma after cardiac surgery.

Kentaro Miura, Kimihiro Shimizu, Seiki Hasegawa, Sachie Koike, Shunichiro Matsuoka, Tetsu Takeda, Takashi Eguchi, Kazutoshi Hamanaka, Momoko Takizawa.

A 70-year-old man diagnosed with right-sided malignant epithelial pleural mesothelioma, underwent pleurectomy/decortication after three courses of neoadjuvant chemotherapy. He had a history of mitral valve replacement and maze procedure with median sternotomy, and the procedures resulted in strong adhesion from the apex to the mediastinal side. In particular, the peeling of the area where the tumor invaded the pericardium required the most attention; however, the involved pericardium could be partially resected without damaging the right atrium. Finally, en bloc macroscopic complete resection with the entire pleura was successfully performed without conversion to extrapleural pneumonectomy.

Keywords: cardiac surgery; malignant epithelial pleural mesothelioma; pleurectomy/decortication

DOI: https://doi.org/10.1111/1759-7714.14231

Clin Chest Med. 2021 12;pii: S0272-5231(21)01198-9. [Epub ahead of print]42(4): 697-710

Malignant Pleural Mesothelioma: Updates for Respiratory Physicians.

Calvin Sidhu, Amber Louw, Y C Gary Lee.

Keywords: Asbestos; Cancer; Effusion; Mesothelioma; Needle tract; Pleural

DOI: https://doi.org/10.1016/j.ccm.2021.08.006