bims-mesote 2025-04-13 papers

Issue of 2025–04–13
six papers selected by
Laura Mannarino, Humanitas Research

World J Surg Oncol. 2025 Apr 09. 23(1): 132

Hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma after cytoreductive surgical procedures: a systematic review.

Hany Hasan Elsayed, Mohamed Elanany Elsaid Elanany, Mohamed Tarek ElSayegh, Aly Sherif Hassaballa, Mohammed Abdel-Gayed.

Surgery-based multimodality therapies for treatment of malignant pleural mesothelioma have been clinically explored in the past decades. In this regard, hyperthermic intrathoracic or intrapleural chemotherapy has been used as one of the multimodality therapies. The question addressed was In patients with malignant pleural mesothelioma who undergo macroscopic complete resection (MCR) does performing a Hyperthermic intrathoracic chemotherapy (HITOCH) lead to improvement in survival? The trial was registered in PROSPERO https://www.crd.york.ac.uk/prospero/ under registration number: CRD42024588823.Three hundred five papers were found using the reported search, 21 were relevant to our topic and only 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Six studies demonstrated a survival benefit for patients receiving HITOCH with a median survival ranging from 13-35 months in comparison to 11 -22.8 months for the non HITOCH group. Three out of the five studies compared extra-pleural pneumonectomy (EPP) to extended pleurectomy decortication (EPD) as the surgical preference for MCR. Only one study by Van Sandick et al. found a negative outcome with HITOCH in patients performing EPP (11 months vs 29 months). There was no reported mortality in relation to complications associated with HITOCH. The most common complication was atrial fibrillation followed by renal impairment. Despite the heterogeneity, small number of cases and lack of prospective randomised controlled trials, the body of evidence identified in this work demonstrates that HITHOC added to MCR in patients with pleural mesothelioma is safe and feasible. Possible improvement in recurrence free survival and overall survival warrant investigation in a randomised controlled trial.

Keywords: Cytoreductive surgery; HITHOC; Hyperthermic intrathoracic chemotherapy; Intraoperative chemotherapy; Mesothelioma

DOI: https://doi.org/10.1186/s12957-025-03748-8

Thorac Cancer. 2025 Apr;16(7): e70062

Cytoplasmic HuR Expression Enhances Chemoresistance in Pleural Mesothelioma Through Increased Expression of CALB2, Promotion of the E2F Pathway, and Suppression of the p53 Pathway.

Susumu Kirimura, Morito Kurata, Hironori Ishibashi, Yusuke Taniguchi, Yuko Kinowaki, Keisuke Sugita, Kenichi Okubo.

INTRODUCTION: Chemotherapy is crucial for treating pleural mesothelioma; however, the outcomes are poor, necessitating an urgent need to study the mechanism of chemotherapy resistance in mesothelioma cells. Human antigen R (HuR), an RNA-binding protein and key post-transcriptional regulator of mRNA, is linked to poor prognosis in cancers like mesothelioma. We investigated the involvement of cytoplasmic HuR expression in drug resistance mechanisms in mesothelioma.
METHODS: We retrospectively evaluated cytoplasmic HuR expression in 30 patients with pleural mesothelioma who underwent surgical resection using immunohistochemistry. We also examined the role of forced cytoplasmic expression of HuR in drug resistance using mesothelioma cell lines and performed RNA-Seq analysis to identify gene expression changes responsible for drug resistance acquisition via HuR cytoplasmic expression.
RESULTS: Patients with mesotheliomas who expressed cytoplasmic HuR exhibited significantly worse disease-free survival following post-operative chemotherapy. Forced cytoplasmic HuR expression in mesothelioma cell lines increased chemotherapy resistance through increased expression of CALB2, upregulation of the E2F pathway and suppression of the p53 pathway.
CONCLUSIONS: Cytoplasmic HuR expression increases the chemoresistance and postoperative recurrence risk of pleural mesothelioma, making it a potential biomarker for predicting therapeutic prognosis. However, the mechanism of HuR transfer to the cytoplasm remains unclear for therapeutic application.

Keywords: chemoresistance; human antigen R (HuR); mesothelioma

DOI: https://doi.org/10.1111/1759-7714.70062

Clin Cancer Res. 2025 Apr 10.

Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.

PURPOSE: Immune checkpoint inhibitors (ICIs) have limited efficacy in pleural mesothelioma. We investigated the role of Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3) in overcoming treatment resistance.
EXPERIMENTAL DESIGN: We performed preclinical studies to elucidate DKK3's role in ICI-resistant mouse mesothelioma. Based on these findings, we conducted a single-arm, phase II clinical trial of a combination of Ad-SGE-DKK3 and nivolumab for chemotherapy-refractory epithelioid pleural mesothelioma, with objective response rate (ORR) as the primary outcome.
RESULTS: DKK3 was significantly reduced in human epithelioid mesothelioma. Overexpression of DKK3 in cancer cells activated the p53 pathway, enhanced glycolysis, increased surface PD-L1, and reduced extracellular vesicle secretion and Colony Stimulating Factor 1 (CSF1). DKK3 sensitized the tumor-immune microenvironment to ICIs and enabled eradication of tumors by PD-1 blockade. In our trial, twelve patients received intratumoral Ad-SGE-DKK3 plus intravenous nivolumab. ORR was 16.6% and 41.7% had stable disease, for a 58.3% rate of durable clinical response (DCB). Median overall survival was 14.5 months, and median progression-free survival was 4.5 months. Grade 3 adverse events occurred in 41.7% of patients. Serial tumor biopsies and serum analyses revealed that DCB patients had increased tumor-infiltrating bulk and effector memory CD8 T cells, reduced circulating memory CD8 T cells, and sustained lower soluble mesothelin and CSF1 levels compared to progressors.
CONCLUSIONS: Combination Ad-SGE-DKK3 plus nivolumab demonstrated a tolerable safety profile and potential efficacy in patients with chemotherapy-refractory epithelioid pleural mesothelioma.
CLINICALTRIALS: gov identifier: NCT04013334.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-4024

Lung Cancer. 2025 Apr 09. pii: S0169-5002(25)00426-X. [Epub ahead of print]203 108534

The global burden of mesothelioma and its association with asbestos bans, 1990-2021: a population-based study.

Weiqiu Jin, Ziyin Ding, Mengwei Zhang, Leilei Shen, Han Wang, Jiaqi Huang, Wendi Xuzhang, Yanruo Huang, Changzi Dong, Chongwu Li, Long Jiang, Zheng Yuan, Xiaodan Ye.

BACKGROUND: Mesothelioma, as a lethal consequence of asbestos exposure, poses a significant threat to high-risk populations. The Global Burden of Disease (GBD) 2021 update provides an opportunity to examine current mesothelioma epidemiology and assess whether asbestos bans have effectively reduced mesothelioma incidence over a longer time span than covered in existing literature.
METHODS: Annual cases and age-standardized rates (ASRs, reported per 100,000 person-years) of incidence, death, disability-adjusted life-years, and probability of death associated with mesothelioma among different age groups were obtained from patients in 204 countries and territories diagnosed with mesothelioma between 1990 and 2021. Estimated annual percentage changes (EAPCs) and period analysis of ASRs were employed to evaluate temporal trends in incidence and mortality. Data on global asbestos consumption and bans were collected from various sources to investigate their relationship with mesothelioma burdens.
RESULTS: In 2021, global incident cases of mesothelioma slightly increased to 31,908 [29,643, 34,115], with 23,184 [21,553, 24,941] in males and 8,724 [7,784, 9,580] in females, up from 31,173 [28,821, 33,090] in 2019, and approximately double the number in 1990 (16,493 [15,325, 17,783]). Australasia, Western Europe, and Southern Sub-Saharan Africa ranked in the top three for all ASRs. The United Kingdom and Australia had the highest ASRs globally, while the Northern Mariana Islands, El Salvador, Syrian Arab Republic, Iran (Islamic Republic of), Saudi Arabia, and Palestine had the lowest ASRs in 2021. Most countries with asbestos bans continued to exhibit declining trends in ASRs from 2019 to 2021.
CONCLUSIONS: Global asbestos bans have demonstrated sustained effectiveness in controlling mesothelioma. Accelerated implementation of asbestos bans in developing nations coupled with deeper exploration of mesothelioma pathogenesis would aid in enhancing primary prevention efforts. Although the mesothelioma burden is more severe in high-income regions, ASRs have decreased more notably in high and upper-middle socio-demographic indexes (SDIs) tiers with generally more comprehensive and earlier asbestos bans compared to other locations. The burden of female mesothelioma has shown slower remission compared to males in many regions recently, underscoring the importance of non-occupational exposures.

Keywords: Asbestos ban; Global burden of disease; Mesothelioma

DOI: https://doi.org/10.1016/j.lungcan.2025.108534

Ann Med Surg (Lond). 2025 Mar;87(3): 1127-1139

Burden of mesothelioma in the Middle East and North Africa: a 32-year analysis of the Global Burden of Diseases Study 2021.

Mohammad Ghiasvand, Shahnaz Fooladi Sarabi, Asal Salehi, Fatemeh Sadat Seyedi Asl, Mohamad AlJasem, Mohammad Yaghoubi, Babak Ehsani Zunuz, Zahra Sanatian, Parisa Alaghi, Mohammad Amin Khadembashiri.

Background: Mesothelioma, a cancer primarily caused by asbestos exposure, has been increasing in the Middle East and North Africa (MENA), raising concerns about the region's occupational and environmental health landscape. With varying Sociodemographic Index (SDI) and differing asbestos regulations across MENA, understanding mesothelioma trends over time is crucial.
Methods: Using data from the Global Burden of Disease (GBD) Study 2021, we analyzed mesothelioma incidence, mortality, and disability-adjusted life years (DALYs) in MENA from 1990 to 2021. Age-standardized incidence rate (ASIR), mortality rate (ASMR), and disability rate (ASDR) were assessed by age, sex, and country. Trend analyses were conducted using joinpoint regression to identify significant shifts in disease burden over the study period.
Results: Between 1990 and 2021, mesothelioma cases rose from 597 to 1365, with ASIR declining at an average annual percent change (AAPC) of -0.49% (P < 0.001). Countries like Oman and Saudi Arabia exhibited rising burdens, while the United Arab Emirates and Turkey saw declines. Males and older age groups had higher ASIR, ASMR, and ASDR rates, indicating gender- and age-based disparities.
Conclusion: While the mesothelioma burden in MENA has declined overall, significant increases in certain countries highlight the need for uniform asbestos regulations and targeted health interventions, especially among high-risk demographics. Further research on occupational exposure and Sociodemographic Index (SDI) improvements could help reduce mesothelioma rates across the region.

Keywords: MENA; Sociodemographic Index; asbestos; cancer epidemiology; disease burden; mesothelioma; occupational health

DOI: https://doi.org/10.1097/MS9.0000000000003079