bims-mesote 2025-03-16 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2025–03–16
nine papers selected by
Laura Mannarino, Humanitas Research

Impact of Neoadjuvant and Adjuvant Pleural Intensity-Modulated Radiotherapy in Multimodality Treatment for Malignant Pleural Mesothelioma.
Prognostic Factors in Pleural Mesothelioma Patients Receiving First-Line Chemotherapy: Establishing the PLECH Baseline Risk Score.
Postoperative Analgesia and Length of Hospital Stay After Surgery for Malignant Pleural Mesothelioma: A Retrospective Observational Study.
Commentator Discussion: Potential advantage of magnetic resonance imaging in detecting thoracic wall infiltration in pleural mesothelioma. A retrospective single-center analysis.
Why the MARS2 Trial Does Not Mean the End of All Mesothelioma Surgery.
Clinical Significance of Bone Metastases in Pleural Mesothelioma.
Potential advantage of magnetic resonance imaging in detecting thoracic wall infiltration in pleural mesothelioma: A retrospective single-center analysis.
Mesothelioma cell heterogeneity identified by single cell RNA sequencing.
Sarcomatoid pleural mesothelioma evaluated using diffusion-weighted whole-body imaging with background body signal suppression.

Thorac Cancer. 2025 Mar;16(5): e70024

Impact of Neoadjuvant and Adjuvant Pleural Intensity-Modulated Radiotherapy in Multimodality Treatment for Malignant Pleural Mesothelioma.

Berta Mosleh, Stefan Schwarz, Anna Cho, Katharina Sinn, Ariane Steindl, Sabine Zöchbauer-Müller, Wolfgang J Köstler, Karin Dieckmann, Martin Heilmann, Joachim Widder, Daniela Gompelmann, Clemens Aigner, Thomas Klikovits, Mir Alireza Hoda.

   BACKGROUND: Few malignancies provoke as many controversies about treatment as pleural mesothelioma. There is limited experience with novel radiotherapy techniques worldwide in adjuvant and particularly in neoadjuvant settings within multimodality treatment. The objective of the current study was to investigate the long-term outcome of neoadjuvant and adjuvant pleural intensity-modulated radiotherapy (IMRT) combined with macroscopic complete resection with or without chemotherapy.
METHODS: We retrospectively analyzed a consecutive cohort of 59 patients who were diagnosed with pleural mesothelioma and underwent multimodality treatment including macroscopic complete resection and neoadjuvant or adjuvant IMRT between 2005 and 2019 at the Department of Thoracic Surgery, Medical University of Vienna, Austria.
RESULTS: In total, 59 patients (median age 59 years; IQR 54-66, male, n = 48; 81%) were included. Forty-seven patients underwent trimodality treatment consisting of induction chemotherapy, extrapleural pneumonectomy, and adjuvant IMRT. Novel neoadjuvant IMRT with (n = 9) or without (n = 3) chemotherapy followed by extrapleural pneumonectomy was performed in 12 patients. Median overall survival (OS) of all patients was 23.2 months (95% CI; 18.1-28.2) and 3- and 5-year survival rates were 33% and 28%, respectively. Survival was comparable between therapies including neoadjuvant versus adjuvant IMRT (median OS 17.5 vs. 24.0 months, p = 0.39).
CONCLUSIONS: Neoadjuvant pleural IMRT has been investigated as a novel treatment option for highly selected cases in pleural mesothelioma. Neoadjuvant IMRT was effective and safe in patients treated in a high-volume institution but showed no relevant survival benefit compared to adjuvant IMRT within multimodality treatment.

Keywords:  intensity‐modulated radiotherapy (IMRT); macroscopic complete resection; multimodality treatment; pleural mesothelioma

DOI:  https://doi.org/10.1111/1759-7714.70024
Oncology. 2025 Mar 11. 1-16

Prognostic Factors in Pleural Mesothelioma Patients Receiving First-Line Chemotherapy: Establishing the PLECH Baseline Risk Score.

Alberto Guijosa, Luis Antonio Cabrera-Miranda, Ana Pamela Gómez-García, Rogelio Trejo Rosales, Wendy Muñoz-Montaño, Diana Flores, Nancy Reynoso-Noverón, Oscar Arrieta.

INTRODUCTION: Pleural Mesothelioma (PM) is a rare and aggressive cancer where prognostic assessment is crucial. Traditional prognostic scores such as the European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have limitations, particularly in reflecting contemporary treatments and demographic diversities, while more recent scores often include novel biomarkers, not widely available and validated. Our goal is to create an effective prognostic score for PM using readily available baseline data.
METHODS: A retrospective cohort study at two Mexican cancer centers included patients with unresectable PM treated with first-line chemotherapy from 2010 to 2023. Baseline variables' associations with overall survival (OS) and progression-free survival (PFS) were analyzed. Prognostic variables from univariate and multivariate analyses formed a baseline risk score. The score's OS prediction was compared to standard CALGB and EORTC scores using ROC curves and Kaplan-Meier analysis.
RESULTS: Among 262 patients (69.1% male, 80.5% epithelioid histology), we developed a 0-7 point PLECH score based on five variables: Platelet count (P: +2), high LDH (L: +1), ECOG ≥ 2 (E: +1), Chest pain at diagnosis (C: +2), and non-epithelioid Histology (H: +1). The score had an AUC of 0.70 for predicting 1-year OS, outperforming CALGB (0.60) and EORTC (0.57) scores, with an optimal cut-off of 2.5 (sensitivity 75%, specificity 55%). High scores (≥3) indicated worse OS (12.3 vs. 20.1 months; p<0.001) and PFS (6.4 vs. 11.3 months; p<0.001).
CONCLUSION: The PLECH score, developed from a substantial Latin-American cohort, is a simple and effective prognostic tool for PM patients, outperforming traditional scores. It identifies a high-risk group potentially better suited to alternative treatments.

DOI: https://doi.org/10.1159/000543637
Anesth Pain Med. 2024 Dec;14(6): e150055

Postoperative Analgesia and Length of Hospital Stay After Surgery for Malignant Pleural Mesothelioma: A Retrospective Observational Study.

Mayuu Kobata, Kenta Takeda, Mana Taguchi, Hiroai Okutani, Takeshi Ide, Akane Kido, Kouichi Fujimoto, Masaki Hashimoto, Ryusuke Ueki, Munetaka Hirose.

   Background: Pleurectomy/decortication (P/D), a surgical procedure for malignant pleural mesothelioma (MPM), is a highly invasive surgery requiring prolonged hospitalization. Previous studies have reported that postoperative analgesia using regional anesthesia contributes to shorter hospital stays after surgery under general anesthesia by reducing acute postoperative pain. However, the association between postoperative analgesia and the length of hospital stay (LOHS) following P/D has not been evaluated.
Objectives: To evaluate the association between postoperative analgesia and postoperative LOHS after P/D.
Methods: This single-institution observational study enrolled consecutive adult patients undergoing P/D under general anesthesia, who postoperatively received either intertransverse process block (ITPB) or continuous intravenous (IV) fentanyl infusion as postoperative analgesia between March 2022 and February 2023.
Results: Among all enrolled patients with ASA physical status II or III (n = 60), postoperative analgesia was administered using either continuous ITPB (n = 19) or continuous IV fentanyl infusion (n = 41). Multivariable logistic regression analysis revealed that postoperative analgesia with continuous ITPB (P = 0.007), a lower incidence of major complications after surgery (P = 0.034), and female sex (P = 0.033) were significantly associated with a shorter postoperative LOHS. In subgroup analysis, patients who received continuous ITPB had significantly lower postoperative LOHS, lower postoperative serum C-reactive protein levels on postoperative day (POD) 3, and reduced acute postoperative pain on POD3 compared to those who received continuous IV fentanyl infusion.
Conclusions: Postoperative analgesia using continuous ITPB appears to be associated with a reduction in LOHS following P/D for MPM under general anesthesia.

Keywords:  Hospital Stay; Postoperative Pain; Regional Anesthesia; Surgical Complications

DOI:  https://doi.org/10.5812/aapm-150055
JTCVS Open. 2025 Feb;23 326-327

Commentator Discussion: Potential advantage of magnetic resonance imaging in detecting thoracic wall infiltration in pleural mesothelioma. A retrospective single-center analysis.

DOI: https://doi.org/10.1016/j.xjon.2024.10.022
Cancers (Basel). 2025 Feb 21. pii: 724. [Epub ahead of print]17(5):

Why the MARS2 Trial Does Not Mean the End of All Mesothelioma Surgery.

David Waller, Rocco Bilancia, Luigi Ventura, Sara Tenconi, Laura Socci, Andrea Bille.

   BACKGROUND/OBJECTIVES: The published report of the MARS2 trial suggested that the addition of extended pleurectomy/decortication to chemotherapy for pleural mesothelioma was harmful. Thus, the report goes on, all disease should be considered as unresectable and no further mesothelioma surgery for survival benefit should be considered. This statement has changed clinical practice in the UK; however, the design of the MARS2 trial has several limitations which should prevent its conclusions being over interpreted. These limitations include the following: the inclusion of too many patients who would fall outside contemporary selection criteria including age, co-morbidity and histology; the unnecessary resection of too much tissue, particularly the diaphragm, and operating on patients too late in the disease process due to less than rigorous staging.
METHODS: We retrospectively analysed the selection and outcome of data of 79 of the 158 (50%) patients who underwent surgery in the surgical arm of the MARS2 study who were operated by the authors in four of the five trial surgical centres. We revised the clinical staging of these patients by applying the criteria in the forthcoming 9th TNM edition including the measurement of pleural thickness.
RESULTS: Based on reported guidelines, the selection for surgery was reset as stage I or II epithelioid PM. We found that 52 (66%) of these patients (group A) would not have been considered for surgery using contemporary selection criteria for the following reasons: non-epithelioid PM in 5; cT/4 in 35; cT2N1 in 10 and 2 cT2N0 (pN1), which would have been detected on preoperative mediastinal biopsy. Of the 27 (34%) trial patients fulfilling current criteria (group B), 12 were cT1N0, 1 was cT1N1, 6 were cT1N0pN1 and 8 were cT2N0, all with epithelioid PM. The median survival of group B was 32 (1-72) months, which was significantly higher than in group A: 8.5 (1-55) months, p < 0.0005 (Mann-Whitney).
CONCLUSIONS: As contemporary selection criteria were not applied in MARS2, its conclusions cannot be universally applied to all those with PM. Together with the favourable postoperative survival in this selected group, we suggest that there is still scope for a further trial of surgery in early-stage epithelioid mesothelioma.

Keywords:  pleural mesothelioma; pleurectomy/decortication; surgical trials

DOI:  https://doi.org/10.3390/cancers17050724
Thorac Cancer. 2025 Mar;16(5): e70033

Clinical Significance of Bone Metastases in Pleural Mesothelioma.

Mitsutomi Miyake, Kozo Kuribayashi, Hiroshi Doi, Aki Kubota, Taiichiro Otuski, Yoshiki Negi, Koji Mikami, Ryo Takahashi, Akifumi Nakamura, Yasuhiro Nakajima, Daichi Fujimoto, Kazuhiro Kitajima, Toshiyuki Minami, Takashi Kijima.

   BACKGROUND: Bone metastasis (BoM) is common in advanced cancer, but its incidence in pleural mesothelioma (PM) remains unclear. This study aimed to determine the incidence of BoM in PM patients and assess its prognosis and risk factors to clarify its clinical significance.
METHODS: A retrospective analysis was conducted on 515 histologically confirmed PM patients enrolled between January 2011 and December 2020. The cumulative incidence of BoM was calculated using the Kaplan-Meier method, with group differences assessed via log-rank tests. Risk factors for BoM were evaluated using multivariate logistic regression.
RESULTS: The median follow-up was 13.3 months (range: 0.2-106.7 months). BoM was detected in 59 patients (11.5%) at diagnosis or during disease progression. Multivariate analysis identified non-epithelial histology (odds ratio [OR]: 2.189, 95% confidence interval [CI]: 1.179-4.065, p = 0.013) as an independent risk factor for developing BoM. Patients with BoM had worse overall survival (OS) compared to those without BoM (median OS: 18.6 months vs. 21.7 months, p = 0.03).
CONCLUSIONS: BoM in PM occurs less frequently than in primary lung cancer, with non-epithelial histology being more commonly associated with BoM. Patients with BoM had a poor prognosis, particularly when BoM was present at diagnosis. This study is limited by its retrospective design, which may introduce biases related to data collection and patient selection. Future prospective studies are needed to validate these findings.

Keywords:  bone metastasis; keynote 483; pleural mesothelioma; prognosis; skeletal‐related events

DOI:  https://doi.org/10.1111/1759-7714.70033
JTCVS Open. 2025 Feb;23 318-325

Potential advantage of magnetic resonance imaging in detecting thoracic wall infiltration in pleural mesothelioma: A retrospective single-center analysis.

Isabel Barreto, Sabine Franckenberg, Thomas Frauenfelder, Isabelle Opitz, Olivia Lauk.

   Objectives: Thoracic wall infiltration in pleural mesothelioma determines the extent of resection and can be an important prognostic factor. Currently, standardized imaging for restaging after neoadjuvant systemic therapy comprises contrast-enhanced computed tomography or positron emission tomography. Additional thoracic magnetic resonance imaging could better discriminate chest wall infiltration preoperatively and increase staging accuracy. For this reason, the added benefit of magnetic resonance imaging was evaluated at our center.
Methods: A retrospective analysis of the extended imaging protocol was performed from July 2018 to March 2024, including a descriptive analysis for the patient's sex, age, tobacco consumption, asbestos exposure, histological subtype, TNM stage, Modified Response Evaluation Criteria for Solid Tumors in solid tumors, and number of neoadjuvant therapy cycles. Preoperative restaging included routine imaging and magnetic resonance imaging. After histological diagnosis of pleural mesothelioma, neoadjuvant therapy was conducted, followed by intended macroscopic complete resection, with intraoperative biopsies of suspicious chest wall lesions. Computed tomography and magnetic resonance imaging results were compared with intraoperative biopsies.
Results: Twenty-six patients (mean age, 65.50 years, 11.50% female) with operable pleural mesothelioma were included. Of the 11 patients with histologically proven chest wall infiltration, 10 (90.91%) had a cT-stage 3 or greater and 4 (36.36%) underwent surgery that resulted in an R2 resection. Thoracic magnetic resonance imaging showed a high sensitivity (90.91%) for the detection of chest wall infiltration, especially when compared with the computed tomography scan (9.09%).
Conclusions: With the adjunctive use of magnetic resonance imaging, we demonstrated a higher sensitivity for detection of chest wall infiltration compared with conventional imaging before surgery. This may improve patient selection for surgery. Nevertheless, larger studies are required to confirm these results.

Keywords:  extension of resection; patient selection for surgery; pleural mesothelioma; preoperative MRI; restaging

DOI:  https://doi.org/10.1016/j.xjon.2024.10.012
Sci Rep. 2025 Mar 13. 15(1): 8725

Mesothelioma cell heterogeneity identified by single cell RNA sequencing.

Licun Wu, Zongjie Wang, Amin Zia, Shana O Kelley, Marc de Perrot.

  Mesothelioma cell heterogeneity encompasses diverse morphological and molecular characteristics observed within tumors, significantly impacting disease progression, treatment outcomes, and the development of targeted therapies. This heterogeneity has long posed challenges for accurate diagnosis and effective treatment, but understanding its complexities offers the potential for novel diagnostic modalities and therapeutic interventions. This study employed single-cell RNA sequencing (scRNA-seq) to investigate mesothelioma cell heterogeneity from various sources, including cell culture (CC), peritoneal lavage (Lav) from the tumor microenvironment, and circulating tumor cells (CTC) in murine models. Gene set enrichment analysis was used to identify distinct gene signatures for each subpopulation. The results revealed unique characteristics for mesothelioma cells depending on their origin. In the CC group, up-regulated genes were primarily involved in tumor cell cycle control, proliferation, and apoptosis. In the CTC group, up-regulated genes were associated with cancer cell stemness. The Lav group showed up-regulated genes facilitating interactions between tumor cells and the microenvironment, such as epithelial-mesenchymal transition and immune responses mediated by IFN-α and IFN-γ. Some pathways were shared among all tumor cells, suggesting the potential for transitioning between functional states under specific conditions. This may be the first study to explore circulating mesothelioma cell heterogeneity using scRNA-seq. The distinct gene signatures identified in each mesothelioma cell subpopulation likely play critical roles in tumor initiation and progression, offering potential novel targets for therapeutic intervention. These findings could help inform the development of more effective, personalized treatments for mesothelioma, ultimately improving patient outcomes.

Keywords:  Gene set enrichment analysis; Mesothelioma (MESO); Signaling pathway; Single cell RNA sequencing (scRNA-seq); Tumor cell heterogeneity

DOI:  https://doi.org/10.1038/s41598-025-92542-3
Respir Investig. 2025 Mar 07. pii: S2212-5345(25)00024-3. [Epub ahead of print]63(3): 323-325

Sarcomatoid pleural mesothelioma evaluated using diffusion-weighted whole-body imaging with background body signal suppression.

Ryosuke Kinoshita, Norihisa Takeda, Hiroko Kiyotoshi, Masahiro Sugihara, Mamiko Kuriyama, Makoto Nakao, Takuji Tsuyuki, Hideki Muramatsu.

  An 83-year-old man with a history of asbestos exposure presented with dyspnea. Thoracic computed tomography showed right-sided pleural effusion and heterogeneous pleural thickening with calcified plaques. Thoracentesis revealed exudative fluid, and the cytology results were negative for malignancy. He didn't want to undergo invasive biopsy for pathological diagnosis. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) detected signal enhancement in the pleural thickening, ruling out metastasis. The patient died after one month, and sarcomatoid pleural mesothelioma was confirmed by autopsy. DWIBS is free of radioactive materials and can be used to evaluate lesion spread and metastases in hospitals equipped with magnetic resonance imaging.

Keywords:  Asbestosis; Diffusion-weighted whole-body imaging with background body signal suppression; Pleural effusion; Sarcomatoid pleural mesothelioma

DOI:  https://doi.org/10.1016/j.resinv.2025.02.013