bims-mesote 2025-01-05 papers

Issue of 2025–01–05
five papers selected by
Laura Mannarino, Humanitas Research

Sci Rep. 2025 Jan 02. 15(1): 392

The presence of pleural effusion is an independent prognostic factor in patients with malignant pleural mesothelioma.

Haoyu Wang, Ruiyuan Yang, Dan Liu, Weimin Li.

Malignant pleural mesothelioma (MPM) is a rare form of thoracic malignancy with a poor prognosis. Pleural effusion (PE) occurs in the majority of patients with MPM; however, its impact on MPM outcomes remains controversial. We searched for eligible patients from the Surveillance, Epidemiology, and End Results (SEER) database, and clinicopathological information and outcomes were collected. Cox proportional hazard regression analyses were utilized to evaluate the association of PE and other factors with overall survival (OS) and cancer-specific survival (CSS) in patients with MPM. A total of 4185 patients were extracted from the SEER database from 2000 to 2021. The median age of the cohort was 73 years, with a predominance of male patients and epithelioid MPM as the main histological subtype. Univariate Cox regression revealed associations between PE, age, sex, marital status, histology, stage, and treatment with both OS and CSS. Besides, multivariate analyses indicated that PE was independently associated with poorer OS and CSS in patients with MPM, regardless of age, sex, histology, stage, and treatment. Subgroup analyses suggested that PE has a remarkable impact on patients undergoing surgery. PE might serve as an independent prognostic factor in patients with MPM, especially in surgery recipients. Consequently, the development of pleural effusion in these patients should receive increased attention. Future studies are needed to validate these findings, particularly concerning the effect of PE in other clinical settings, such as immunotherapy.

Keywords: Malignant pleural mesothelioma; Pleural effusion; Prognosis; SEER

DOI: https://doi.org/10.1038/s41598-024-84108-6

Interdiscip Cardiovasc Thorac Surg. 2024 Dec 28. pii: ivae223. [Epub ahead of print]

Surgical indications for pleurectomy decortication in pleural mesothelioma based on the newly revised 9th edition tumor-node-metastasis classification.

Masatoshi Kanayama, Masaru Takenaka, Takehiko Manabe, Katsuma Yoshimatsu, Rintaro Oyama, Hiroki Matsumiya, Masataka Mori, Koji Kuroda, Fumihiro Tanaka.

OBJECTIVES: The MARS2 trial questioned the efficacy of curative intent surgery for pleural mesothelioma, while real-world clinical data from Japan suggest a favourable prognosis in surgical cases, indicating survival benefits in selected patients. The newly revised 9th edition of the tumour-node-metastasis classification introduces a novel indicator based on pleural thickness.
METHODS: We conducted a retrospective evaluation of patients with pleural mesothelioma who underwent pleurectomy decortication between 2012 and 2022. Patient characteristics, complications, and treatment outcomes were assessed. Additionally, outcomes were analysed based on the 9th edition tumour-node-metastasis classification.
RESULTS: A total of 62 patients were included in the analysis. The median overall survival was 37.3 months, with a median relapse-free survival of 15.5 months. Patients with the epithelioid subtype (overall survival: 61.6 months; relapse-free survival: 26.0 months) and pStage IA (overall survival: not reached; relapse-free survival: 69.1 months) had significantly better outcomes. The 9th edition tumour-node-metastasis classification showed a stronger prognostic correlation than the 8th edition, with a median overall survival of 77.0, 31.9, 20.4, and 25.3 months for stages I, II, IIIA, and IIIB (p = 0.0016), and median relapse-free survival of 34.3, 12.3, 13.7, and 6.9 months for stages I, II, IIIA, and IIIB (p = 0.013), respectively.
CONCLUSIONS: Surgical intervention remains crucial in the treatment of pleural mesothelioma, particularly for patients with epithelioid histology and early stages of the disease. This study evaluates surgical indications for pleural mesothelioma using the newly revised 9th edition of the tumour-node-metastasis classification, indicating that it enhances the precision of surgical candidate selection and potentially improves patient outcomes.

Keywords: Pleural Mesothelioma; Surgical Indications; the 9th Edition TNM Classification

DOI: https://doi.org/10.1093/icvts/ivae223

Ann Thorac Surg Short Rep. 2024 Dec;2(4): 613-617

The Role of Endobronchial Ultrasound for Mediastinal Staging in Mesothelioma.

Desiree Steimer, Peter Tramontozzi, Patrick Gedeon, Matthew Pommerening, Ariadne DeSimone, Raphael Bueno, Hisashi Tsukada.

BACKGROUND: Invasive mediastinal staging is a crucial component of the preoperative evaluation for potential surgical candidates with pleural mesothelioma (PM). Endobronchial ultrasound (EBUS) is less invasive than mediastinoscopy for staging; however, its accuracy in patients with PM remains undefined. We present our institutional experience with EBUS staging in patients with PM.
METHODS: Patients with PM who underwent EBUS for mediastinal staging between January 2017 and February 2021 (Brigham and Women's Hospital, Boston, MA) followed by surgical resection were retrospectively reviewed. EBUS cytology was compared with final pathology reports for the corresponding lymph node removed at the time of pleurectomy to assess EBUS accuracy.
RESULTS: During the study period, 91 patients with PM met inclusion criteria. EBUS diagnostic yield was highest at nodal station 7 (84%) and lowest at station 4L (40%). There were 74 patients taken for surgical resection, and 41 patients had matching lymph nodes for analysis. In our series, EBUS had a sensitivity of 81%, a specificity of 93%, a positive predictive value of 90%, and a negative predictive value of 84%.
CONCLUSIONS: EBUS is a reasonable alternative to mediastinoscopy for mediastinal staging in patients with mesothelioma.

DOI: https://doi.org/10.1016/j.atssr.2024.06.024

Sci Rep. 2025 Jan 02. 15(1): 169

Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure.

Dahlia M Nielsen, Mei Hsu, Michael Zapata, Giovanni Ciavarra, Leonel van Zyl.

Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.

Keywords: Asbestos; BAP1; Bayesian statistics; Historical control data; Mesothelioma; Mouse studies

DOI: https://doi.org/10.1038/s41598-024-84069-w

JTO Clin Res Rep. 2024 Dec;5(12): 100692

Individualized Cell-Free DNA Monitoring With Chromosomal Junctions for Mesothelioma.

Kaushal Parikh, Faye R Harris, Giannoula Karagouga, Amy Schrandt, Jay Mandrekar, Sarah Johnson, Alexa McCune, Dorsay Sadeghian, Debarshi Roy, Katarzyna Polonis, Athanasios Gaitatzes, Aaron O Bungum, Eric S Edell, Mitesh J Borad, Tobias Peikert, Farhad Kosari, John Cheville, George Vasmatzis, Aaron S Mansfield.

Introduction: The spatially complex nature of mesothelioma and interventions like pleurodesis, surgery, and radiation often complicate imaging-based assessment. Further, cell-free DNA (cfDNA) based monitoring strategies are inadequate for mesothelioma, given the presence of a few recurring nonsynonymous somatic variants. However, patient-specific chromosomal rearrangements are commonly found in mesothelioma. Our study objective was to develop an individualized cfDNA assay to enable blood-based monitoring using circulating tumor DNA (ctDNA) in mesothelioma. We hypothesized that the unique chromosomal rearrangement junctions found in mesothelioma could be employed for individualized ctDNA detection and disease monitoring.
Methods: DNA was extracted from tumor specimens for whole genome sequencing. Chromosomal junctions, prioritized by highest allele frequency and low homology to the rest of the genome, were selected for detection. Primers and Taqman probes were designed to span the junctions, forming personalized junction panels. Patient plasma obtained before therapy and at response assessment was tested for the presence of personalized junctions via quantitative polymerase chain reaction.
Results: Our study included nine patients, four with peritoneal and five with pleural mesothelioma. 763 chromosomal junctions were identified in the tumors of all cases. We selected three to five junctions per sample for quantitative polymerase chain reaction. We detected 25/30 (83%) of selected junctions in the plasma of seven out of nine patients (78%). Cell-free junction detection at follow-up was concordant with disease status: cfDNA junctions were detected in three patients with persistent disease, and not detected in a patient with no evidence of disease after surgery.
Conclusions: With further validation, individualized ctDNA junction assays could supplement imaging for disease monitoring in mesothelioma.

Keywords: Cell-free DNA; Chromosomal rearrangements; Mesothelioma

DOI: https://doi.org/10.1016/j.jtocrr.2024.100692