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Pleural mesothelioma (PM) is a rare and highly aggressive malignancy originating from the pleural lining, with a median overall survival of merely 1 year. This cancer primarily arises from mesothelial cells following exposure to carcinogenic, biopersistent mineral fibers, particularly asbestos. The histological subtypes of mesothelioma are epithelioid (approximately 60%), sarcomatoid (20%), and biphasic (20%), exhibiting epithelioid and sarcomatoid characteristics. Classification is important for prognosis and guides the therapeutic strategy. Due to the typical late presentation, most patients with PM are ineligible for localized treatments such as surgery or radiotherapy. Systemic therapy, including cytotoxic chemotherapy, targeted therapies, and immunotherapy, is thus critical for managing advanced PM. For unresectable PM, decisions regarding systemic treatment are guided by patient suitability and histological characteristics. First-line therapies for advanced PM currently include the cisplatin-pemetrexed combination and the nivolumab-ipilimumab regimen. Historically, cisplatin-pemetrexed has been administered as first-line treatment, though recent advancements have introduced new therapies that significantly prolong patient survival. Innovative approaches combining immunotherapy and chemotherapy offer promising avenues for further improvement. Future treatment strategies should incorporate novel paradigms, such as combination chemo-immunotherapy, targeted agents, and potential cellular therapies, alongside companion biomarkers tailored to the histologic and molecular diversity of mesothelioma. This review explores the latest advancements in drug therapy for PM and provides an overview of current systemic treatment options., Competing Interests: Declaration of competing interest The author has no conflict of interest., (Copyright © 2025 [The Author]. Published by Elsevier B.V. All rights reserved.)

Background: Malignant peritoneal mesothelioma (MPM) is a rare but aggressive cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was the preferred choice for selected patients. The purpose of this study was to thoroughly examine the impact of the combined treatment and the prognostic variables, particularly the neutrophil-to-lymphocyte ratio (NLR)., Methods: Characteristics of MPM patients who underwent CRS combined HIPEC treatment, followed by adjuvant chemotherapy were retrospectively collected. The univariable analysis was performed to identify the decisive influential factor. Using Kaplan-Meier analysis, the cumulative probability of survival was determined. Using Univariate Cox analysis, the prognostic factors-particularly NLR-and its correlation with survival were assessed. In the multivariate Cox proportional hazards model, predictive factors that demonstrated significance in univariate analysis were used. The degree of connection between predictors and survival was evaluated through the use of hazard ratios (HRs) and 95% confidence intervals (95% CIs)., Results: A total of 64 patients were enrolled in this study. The 1, 3, 5 years survival rates were 70.3%, 65.6%, 59.4%, respectively. According to multivariate Cox analysis, patients' survival was found to be substantially associated with post-operative NLR (HR 0.180, 0.067-0.531), Ki-67 (HR 0.184, 0.024-0.817), post-operative neutrophil count (HR 0.228, 0.075-0.696), and bidirectional pathological type (HR, 0.375, 0.146-0.964)., Conclusions: NLR is associated with the patients' prognosis after CRS combined HIPEC treatment., Competing Interests: Declarations. Ethics approval and consent to participate: This study adhered to the Declaration of Helsinki and was approved by the ethic committee of Beijing Shijitan Hospital, Capital Medical University. Written informed consent was obtained from all the participants for the publication of this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Malignant pleural mesothelioma is a rare and aggressive tumour of the pleura, commonly linked to asbestos exposure. However, its diagnosis is challenging, especially without known exposure. We present the case of a woman in her early 70s with no history of asbestos exposure, who presented with progressive breathlessness and left-sided chest pain. Radiological assessment revealed a large pleural effusion and nodular pleural thickening. Malignant pleural mesothelioma was confirmed through histopathological analysis of biopsies obtained via medical thoracoscopy. The patient was initiated on a palliative chemotherapy regimen, underwent talc slurry pleurodesis for recurrent effusion, and is currently under follow-up. This case emphasises the importance of a high index of suspicion for malignant pleural mesothelioma in patients with unexplained pleural effusion, even in the absence of typical risk factors, and the need for a timely diagnosis due to the disease's dismal prognosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Pleural mesothelioma is a fatal disease with limited treatment options. Recently, pleural mesothelioma management has improved with the development of immune checkpoint inhibitors (ICI). In first-line therapy, dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy. Unfortunately, only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required. In this study, we evaluated the effect of hyperthermic intrathoracic chemotherapy (HITOC), a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs. To do this, we developed a murine pleural mesothelioma model of HITOC. We found that HITOC significantly improved tumor control and animal survival through a mechanism involving the development of a cytotoxic immune response. Additionally, HITOC enhanced immune checkpoint expression by T lymphocytes and synergized with dual PD-1 and CTLA-4 inhibition, leading to further improvement in animal survival. Finally, the analysis of peritoneal mesothelioma patient samples treated by pressurized intraperitoneal aerosol chemotherapy revealed a similar immunomodulation. In conclusion, HITOC remodels the tumor immune microenvironment of pleural mesothelioma by promoting T-cell infiltration into the tumor and could be considered in combination with ICIs in the context of a clinical trial., (©2024 American Association for Cancer Research.)

Background: No guidelines exist regarding the management of the uninvolved uterus or adnexa (fallopian tubes and/or ovaries) in patients with peritoneal metastases (PM) from non-gynecologic malignancies. It is unclear whether salpingo-oophorectomy, hysterectomy, or both should be performed when a complete pelvic peritonectomy is otherwise warranted., Methods: A 25-item electronic survey was sent to 225 surgeons worldwide who routinely perform cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Participants were recruited through listservs of expert groups. Individual surgeon approaches to the management of the grossly uninvolved uterus and adnexa in pre- and post-menopausal women with PM from low- and high-grade appendiceal neoplasms, colorectal cancer, and peritoneal mesothelioma were collected using a 5-point Likert scale., Results: A total of 135 complete responses (60% response rate) were obtained from surgeons practicing in 27 countries. Respondents reported a median practice of 10 years (interquartile range [IQR] 6-15 years) and a median performance of 20 (IQR 12-30) CRS/HIPEC operations per year. Rates of salpingo-oophorectomy differed by histology and a woman's menopausal status, ranging from 29 to 42% in pre-menopausal women to 71-77% in post-menopausal women (P < 0.001). Notably, the number of surgeons who would perform a hysterectomy was lower, ranging from 12 to 27% for pre-menopausal women and from 32 to 44% for post-menopausal women, dependent on histology (P < 0.001)., Conclusions: Surgeons are overall more aggressive with adnexal resection than with hysterectomy in both pre- and post-menopausal women with PM from non-gynecologic malignancies. Further prospective studies are required to determine the best approach to optimize surgical and oncologic outcomes while also accounting for the fertility and hormonal impact., Competing Interests: Disclosure: Shannon N. Radomski received financial support from the National Cancer Institute (NCI) grant 5T32CA126607-12 and the American College of Surgeons Resident Research Scholarship. Stephanie Wethington - In the 36 months prior to publication, I had 6 weeks of employment by Astrazeneca. Olivier Glehen - consultant for GAMIDA., (© 2024. Society of Surgical Oncology.)

Background: Pleural mesothelioma is a rare and incurable cancer, with complex physical and psychological symptoms. Despite recent advances in treatment, prognosis remains poor (average 8-15 months) with a lack of research on palliative and end-of-life care., Aim: To examine markers suggestive of quality palliative and end-of-life care, including receipt of specialist palliative care, advance care planning, fewer unplanned hospital admissions at end-of-life. To compare variables with socio-economic position to identify if inequalities exist., Design: A cohort study, retrospectively reviewing the medical notes from diagnosis to death for all patients diagnosed with pleural mesothelioma between 01/01/2016 and 31/12/2021., Setting/participants: Over 5 years, n  = 181 patients were diagnosed with pleural mesothelioma across Teesside (north-east England), n  = 30 were alive at study commencement and excluded. For the 151-patient cohort, demographics were as follows: 92% male, 79% aged 70-89 years and 26% in the lowest socio-economic quintile (based on area-level deprivation)., Results: Median survival was 246 days. Within the final 90 days of life, 69% of patients had at least 1 unplanned hospital admission, with 20% having 3+ (range 0-7). Those with the highest socio-economic position had less admissions on average. Specialist palliative care was received by patients, at home 34%, in hospital 26%, in hospice 11%. Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decisions, were in the final 24 h of life for 18% of patients (median 7 days). Disease specific findings included police attendance for expected deaths and lack of signposting., Conclusion: Patients with pleural mesothelioma have unplanned admissions to hospital towards the end of life, with possible inequalities; they receive late advance care planning and face challenges unique to their disease. It is important that patients receive high quality palliative end-of-life care through accessing specialist palliative care or have guidance/signposting to other potential sources of support., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms' tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4 + and/or CD8 + T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8 + T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Antwerp University Hospital/University of Antwerp (EC 10/40/266) and the Belgian Federal Agency for Medicines and Health Products (FAGG 08 − 0005) and registered at ClinicalTrials.gov (NCT01291420) and EudraCT (2011-000547-24). The sponsor’s protocol code was CCRG 11 − 001. All participants provided informed written consent in accordance with the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: VFVT and ZNB are coinventors of a now-elapsed patent covering the messenger RNA electroporation technique (Improved Transfection of Eukaryotic Cells with Linear Polynucleotides by Electroporation, WO/2003/000907)., (© 2025. The Author(s).)

Combination immune checkpoint inhibitors (nivolumab and ipilimumab) are currently a first-line treatment for mesothelioma; however, not all patients respond. The efficacy of treatment is influenced by the tumor microenvironment. Murine mesothelioma tumors were irritated with various radiotherapy doses. Radiotherapy induced vasculature changes were monitored by power Doppler and photoacoustic ultrasound and analyzed via mixed-effects models. Tissue staining was used to investigate the immune cell infiltrate of tumors. The optimal radiotherapy schedule was combined with immune checkpoint inhibitors, and the survival of mice was analyzed. Using low-dose, low-fraction radiotherapy allowed favorable modification of the murine mesothelioma tumor microenvironment. Irradiating tumors with 2 Gy × 5 fractions significantly improved blood flow and reduced hypoxia, consequently increasing the presence of CD8 + and regulatory T cells in the tumor. Understanding the transient nature of these changes is crucial for optimizing the timing of therapeutic delivery. The combination of radiotherapy with dual immunotherapy (anti-PD-1 plus anti-CTLA-4) proved highly curative when administered concurrently. A diminishing rate of cures was noted with an increasing delay between radiotherapy and subsequent immunotherapy. Concurrent low-dose, low-fraction radiotherapy emerges as a translatable approach for improving the efficacy of immune checkpoint inhibitors in patients., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethical approval: All experimental protocols involving mice were approved by the Animal Ethics Committees of HPIMR, the University of Western Australia (UWA), and the Telethon Kids Institute (Perth, Australia) (AE163) and were conducted in accordance with the Australian Code for the Care and Use of Animals for Scientific Purposes (8th edition, 2013) and UWA animal ethics guidelines and protocols., (© 2024. The Author(s).)

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer with long latency and poor prognosis. The real-world treatment patterns and humanistic burden of MPM in an international cohort of patients were recently published. Spanish data are currently lacking and are reported here., Methods/patients: Data were collected from three sources: physician-abstracted demographic, clinical and treatment characteristics of patients with MPM; patient-completed questionnaires on treatment satisfaction, symptoms, caregiver use, and impact of the disease; and caregiver-completed questionnaire reporting their activity and its impact on their daily life., Results: The 241 patients in Spain were primarily elderly (median age: 67 years), male, retired/unemployed/on long-term sick leave, and diagnosed at stage IV with unresectable disease. Exposure to asbestos was detected (54%, 101/188). First-line treatment (1L) consisted primarily of doublet chemotherapy (86%, 207/241). Of 102 patients who completed 1L at data abstraction, 67 were receiving maintenance therapy, most commonly singlet chemotherapy with pemetrexed. Best supportive care was given to 29 patients, primarily after 1L (86.2%, 25/29). Symptom burden was high and health-related quality of life was poor and declined with progression: mean (SD) EQ-5D score and EQ-5D visual analogue scale score were 0.615 (0.285) and 60.8 (17.1) in 1L and 0.497 (0.370) and 56.1 (19.5) in second line. Overall, 67% of patients (162/241) required daily assistance from their caregiver, who reported an impact on their psychological well-being., Conclusions: Patients with MPM in Spain were overall treated according to treatment guidelines at the time. Nevertheless, a considerable burden of disease was reported by patients and caregivers., Competing Interests: Declarations. Conflicts of interests: S.C. reports an advisory role and/or travel compensation: F. Hoffmann La Roche AG, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb recipient, and Amphera. J.C. reports an advisory role and/or travel compensation: Pfizer, Bristol Myers Squibb, and F. Hoffmann La Roche AG. G.T.S. Adelphi Real World employee. N.A.A. BMS employee. D.V.L. BMS employee. M.D. BMS employee. Ethical approval: This study was approved by the Western Institutional Review Board (IRB Number: 20183141). The study was performed in accordance with the relevant guidelines and regulations, including the Declaration of Helsinki. Informed consent: Informed consent was provided by patients and caregivers when providing their data., (© 2024. The Author(s).)

Malignant peritoneal mesothelioma is an aggressive and rare disease that affects the serosal membranes. The outcomes of patients who suffer from this disease have improved because of the advances in imaging, genetics, and treatment strategies such as systemic therapy and cytoreduction surgery and hyperthermic intraperitoneal chemotherapy. Multidisciplinary care remains essential for enhancing survival and quality of life., Competing Interests: Disclosures Neither author has a conflict of interest relevant to the contents of this article., (Copyright © 2025 Elsevier Inc. All rights reserved.)

The goal of the American Association of Bronchology and Interventional Pulmonology Essential Knowledge in Interventional Pulmonology Series is to provide clinicians with concise, up-to-date reviews of important topics in the field of interventional pulmonology. This 3-year alternating rotation of primary topics will start with a focus on selected topics in malignant pleural disease. In this article, we update the reader on malignant pleural effusion in 3 parts: part 1-diagnosis, focusing on imaging and fluid biomarkers; part 2-management, with review of multimodal approaches, cost considerations, and evolving targeted therapies; and part 3-pleural mesothelioma. These reviews complement the Essential Knowledge in Interventional Pulmonology Lecture Series presented at the 2023 AABIP Annual Conference, available for viewing on the AABIP website (https://aabip.memberclicks.net/essential-knowledge-in-interventional-pulmonology-series)., Competing Interests: Disclosure: A.A.C.: consultant for Intuitive Inc. The remaining authors have no conflict of interest or other disclosures., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. From March 2017 until August 2023, 55 patients with localized pleural mesothelioma underwent pleurectomy and decortication. Thirty patients performed only surgery while 25 consecutive patients had surgery followed by HITOC with cisplatin (125 mg/m 2 ) infused for 70 min at a temp of 40-43 °C. We analyzed postoperative morbidity, HITOC-related complications, and the influence of HITOC on survival. The trial was registered on 19/08/2022 as NCT05508555. The HITOC group had a mean age of 53.1 ± 8.2 years while the surgery group (non-HITOC) had a mean age of 52.1 ± 8.6 years. The HITOC group had 17 (68%) men, whereas the surgery group included 18 (60%) males. The 30-day mortality in the HITOC group was 0% vs 1 case (3.3%) in the surgery group. HITOC-related transient complications occurred in 4/25 (16%) of the HITOC group (atrial fibrillation, renal impairment and transient hypotension). Progression-free survival in the HITOC group was 8 months (95% CI 4.3-11.6) vs 6 months (95% CI 2.5-9.9) in the surgery-only group (p = 0.79). The overall survival time in the HITOC group was 28 months (95% CI 21.5-34.5) vs 22 months (95% CI 17.5-26.5) in the surgery-only group (p = 0.75). Risk factors analysis for recurrence in the HITOC group confirmed a significant role for early stages (p = 0.03). HITOC following pleurectomy and decortication is a safe therapeutic option that may improve survival for selected patients with localized epithelial pleural mesothelioma. Patients with earlier-stage mesothelioma are more likely to benefit from radical surgery and HITOC., Competing Interests: Declarations. Conflict of interest: None declared. Ethics approval and consent: Informed consent was obtained from all subjects and/or their legal guardian(s). Ethics approval from Ain shams university ethics committee on 1/8/2022 by the with IRB number: FWA 000017585., (© 2024. The Author(s).)

Aim: To evaluate the real-world treatment patterns and outcomes for patients with pleural mesothelioma (PM) in the era of immunotherapy., Methods: This retrospective audit included patients with PM diagnosed within three tertiary referral centers in Queensland, Australia from January 2017 to July 2023. Patient and treatment characteristics and outcomes were recorded. Data was analyzed using descriptive statistics and the Kaplan-Meier survival method., Results: A total of 90 patients were included: 84% were male, the median age was 75 years (range 70-79) and 85% had baseline Eastern Group Cooperative Group of 0-1. Subtypes included 54% epithelioid, 17% biphasic, 12% sarcomatoid, and 17% unspecified/unknown. First-line treatment was received by 57/90 patients (63%) and 33/90 patients (37%) received the best supportive care (BSC). Chemotherapy was most used (63%) overall, but first-line immunotherapy was more commonly used since ipilimumab/nivolumab was reimbursed by the Australian Pharmaceutical Benefits Scheme in July 2021. After first-line treatment, only 40% received second-line treatment and 60% received BSC. 12-month overall survival (OS) and progression-free survival for all patients were 53% (95% confidence interval [CI]: 43-65) and 25% (95% CI 15-40) respectively. 12-month OS was 72%, 64%, and 29% for immunotherapy, chemotherapy, and BSC, respectively. There was no significant difference in survival between chemotherapy and immunotherapy (hazard ratio 1.28, 95% CI: 0.65-2.5, p = 0.5)., Conclusion: In our unselected real-world cohort, both chemotherapy and immunotherapy are active against PM, but the prognosis remains guarded. There remains a need for better treatment options, especially in the first-line setting. Enrolment in clinical trials is crucial to improving outcomes in this debilitating disease., (© 2024 The Author(s). Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Background: Despite remarkable achievements in applying chimeric antigen receptor (CAR)-T cells to treat hematological malignancies, they remain much less effective against solid tumors, facing several challenges affecting their clinical use. We previously showed that multichain DNAX-activating protein (DAP) CAR structures could enhance the safety and efficacy of CAR-T cells when used against solid tumors. In particular, mesothelin (MSLN)-targeted CAR-T cell therapy has therapeutic potential in MSLN-positive solid tumors, including ovarian cancer and mesothelioma., Methods: In vitro cell killing assays and xenograft model were utilized to determine the anti-tumor efficacy of MSLN targeting DAP-CAR-T cells and other CAR-T cells. ELISA and flow cytometry analysis were used to assess the cytokine secretion capacity and proliferation ability. Eight patients with MSLN expression were enrolled to evaluate the safety and efficacy of MSLN-DAP CAR-T cell therapy. Single-cell sequencing was performed to explore the dynamics of immune cells in patients during treatment and to identify the transcriptomic signatures associated with efficacy and toxicity., Results: We found that multichain DAP-CAR formed by combining a natural killer cell immunoglobulin-like receptor truncator and DAP12 exhibited better cytotoxicity and tumor-killing capacity than other natural killer cell-activated receptors associated with DAP12, DAP10, or CD3Z. The safety and efficacy of MSLN-DAP CAR-T cell therapy in patients with ovarian cancer and mesothelioma were evaluated in a single-arm, open-label clinical trial (ChiCTR2100046544); two patients achieved partial response, while four patients had a stable disease status. Furthermore, single-cell sequencing analysis indicated that KT032 CAR-T cell infusion could recruit more immune cells and temporarily remodel the TME., Conclusions: Our study highlights the safety and therapeutic efficacy of multiple-chain DAP-CAR-T cell therapy targeting MSLN to treat patients with ovarian cancer and mesothelioma., Trial Registration: ChiCTR.org.cn, ChiCTR2100046544 . May 21, 2021., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Institution Review Board of The First Affiliated Hospital of Nanjing Medical University (2021-SR-084). This study conformed to the principles of the Helsinki Declaration. Healthy donors or patients consented to participate in the study. All participants provided written informed consent prior to participation. The animal experiment in this study was approved by the Institutional Ethics Committee of Nanjing Medical University (IACUC2103036). Consent for publication All participants provided written informed consent for publication. Competing interests Authors EX-W, C-W, and JZ-Z were employed by Nanjing CART Medical Technology Co., Ltd. The other authors declare that they have no competing interests., (© 2024. The Author(s).)

Pleural mesothelioma is a rare and aggressive cancer that affects the pleura. In recent years, there has been increasing interest and attention in detecting and diagnosing early-stage or precancerous forms of mesothelioma because of its severe prognosis and short life expectancy at the time of diagnosis. Mesothelioma in situ represents a clear opportunity to improve and innovate the diagnostic approach and the multimodality treatment of mesothelioma: the diagnosis of pleural mesothelioma at the 'in-situ phase' means early disease detection and thus paves the way to new possible curable strategies. Since 2021, when mesothelioma in situ was finally identified and described as a new histological entity, its diagnosis and management became a challenge and the subject of ongoing research; several aspects remain open and still outstanding as regards diagnostic techniques, time and probability of progression, need for and methods of follow up, aggressive and early surgery. This narrative review aims to provide a comprehensive overview of mesothelioma in situ covering its definition, risk factors, diagnostic criteria, and tricky aspects of early detection. It also highlights its clinical significance, new perspectives, and potential future indications in the context of pleural mesothelioma multidisciplinary management., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mesothelioma is a cancer of growing global incidence, especially in developing countries, with unique complex psychosocial impacts on patients and their carers., Aims: To provide a comprehensive understanding of the psychosocial needs of people living with pleural mesothelioma and family carers., Methods: A mixed methods design with 61 semi-structured interviews and psychometrically validated questionnaires to assess pleural mesothelioma patients' (n = 36) quality of life and frailty and carers' (n = 25) caregiving experiences, quality of life, and pre-loss prolonged grief symptoms., Results: People with mesothelioma (29 men, 7 women, aged 46-89 years) indicated moderate quality of life; 18 (50%) met criteria for frailty. Current carers (21 women, 4 men; aged 41-79 years) generally reported positive caregiving experiences and high quality of life; 5 (20%) scored in the range indicative of risk for prolonged grief disorder. Four themes were generated: a desire for tailored information with bespoke detail, assistance to coordinate tasks of treatment, improved social and peer support, and effective psychological services. Needs varied, with main concerns being about breaking the news to spouses/children, the impact of the disease and death on family, loss of personal future, managing psychological symptoms, and avoiding burden., Conclusions: These specific and unmet psychosocial needs provide a strong basis for individualised care pathways to address these needs via the integration of psychology into the multidisciplinary care team and the development and evaluation of mental health and wellbeing interventions for mesothelioma patients and carers. Doing so will reduce psychosocial distress and improve residual vitality., (© 2024 John Wiley & Sons Ltd.)

Background: The comprehensive treatment strategy, mainly cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), combined with systemic and intraperitoneal chemotherapy, is the standard treatment for malignant peritoneal mesothelioma (MPM), which can significantly prolong the survival of patients. The aim of this study is to investigate the clinical significance of postoperative normothermic intraperitoneal chemotherapy (NIPEC) in MPM patients., Methods: Data of 152 MPM patients who underwent CRS + HIPEC and postoperative intravenous chemotherapy were retrospectively analyzed. Patients were divided into the Non-NIPEC group and the NIPEC group according to whether they received NIPEC after surgery. The baseline characteristics of the two groups were compared, and the survival outcome was analyzed in subgroups according to completeness of cytoreduction (CC) score. Multivariate survival analysis was used to determine the independent prognostic factors., Results: In CC 0-1 and CC 2-3 subgroups, there was no significant difference in baseline characteristics between Non-NIPEC and NIPEC groups. Survival analysis showed that for CC 0-1 patients, there was no significant difference in overall survival (OS) between Non-NIPEC and NIPEC groups (P = 0.503). However, for CC 2-3 patients, the median OS of the NIPEC group was significantly longer than that of the Non-NIPEC group (24.5 vs. 10.3 months, P = 0.005). Pathological type, preoperative thrombosis and postoperative NIPEC (HR = 0.423, 95%CI: 0.228-0.786, P = 0.006) were independent prognostic factors for CC 2-3 patients., Conclusions: For MPM patients receiving CRS + HIPEC, postoperative intraperitoneal combined with intravenous chemotherapy may improve the survival of CC 2-3 patients, but CC 0-1 patients do not seem to derive the same benefit., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Well-differentiated papillary peritoneal mesothelial tumors (WDPMTs) are understudied and discrete from peritoneal mesotheliomas (PMs). We report clinicopathologic characteristics and outcomes of a large prospective WDPMT cohort., Methods: Patients with WDPMT identified between August 2007 and December 2020 were followed through January 2023. Clinical characteristics and outcomes were annotated. Overall survival (OS) was assessed from pathologic diagnosis. Germline variants were analyzed, and targeted next-generation sequencing (NGS; MSK-IMPACT) data were compared to PMs and diffuse pleural mesotheliomas (DPMs)., Results: Among 54 patients, median age at diagnosis was 55 (range 20-76), 50% were female (n = 27), and 46% were smokers (n = 25; median 8 pack/years). Most (94%, n = 51) WDPMTs were found during surgical explorations for other indications, primarily other malignancies. Two patients underwent surgical resection for WDPMT; none received systemic therapy for WDPMT. Median OS was not reached (19/54; median follow up 4.5 years). Somatic NGS was available for 35% (19/54) of patients. TRAF7 alterations were enriched in WDPMT (89%; 17/19) compared with PM (0%; 0/50; p < 0.0001) and DPM (0%; 0/74; p < 0.0001). In WDPMT compared with PM and DPM, there were less BAP1 (0% [0/0] vs. 4% [8/50] vs. 46% [34/74]; p = 0.001 and p < 0.0001, respectively) and NF2 (0% [0/0] vs. 24% [12/50] vs. 31% [23/74]; p = 0.03 and p = 0.001 respectively) alterations. Pathogenic germline variants were present in 23% (4/17) of WDPMTs., Conclusions: Well-differentiated papillary peritoneal mesothelial tumors were primarily incidental findings. There was no WDPMT-related mortality, so there was no distinct role for routine cytoreductive surgery or systemic therapy. Genomic profiles can help to differentiate WDPMT from DPM and PM., (© 2024. The Author(s).)

Background: The 2018 ASCO pleural mesothelioma (PM) treatment guideline states that "a trial of expectant observation may be offered" in patients with asymptomatic inoperable epithelioid mesothelioma with low disease burden. The aim of our analysis was to evaluate clinical characteristics and outcomes in PM-patients managed with initial observation and deferred treatment initiation., Methods: We retrospectively collected clinicodemograhic and outcome data of patients with inoperable PM. Patients were assigned to 2 treatment decision groups: decision to start immediate systemic treatment (Immediate Treatment Group) versus observation and deferring treatment (Deferred Treatment group)., Results: Of 222 patients with advanced PM, systemic treatment was started immediately in the majority of patients (189, 85%; immediate group); treatment was deferred in 33 (15%) patients (deferred group); systemic therapy was chemotherapy-based in 91% and 79% respectively. Patients in the deferred group were older (70 vs 67 years, p = .05), less likely to have stage IV disease (28% vs. 51%, p = .08) and more often had epithelioid histology (90% vs. 70%, p = .03). Nineteen patients (58%) in the deferred group eventually received treatment. With a median follow-up time of 10.9 months median overall survival (OS) in the entire cohort was 12.4 months and was significantly longer in the deferred group (20.6 months vs. 11.5 months, p = .02). No difference in median progression-free survival (PFS) in first-line treatment between groups was seen (5.4 and 5.3 months)., Conclusion: This real-world analysis suggests that deferral of systemic therapy and close observation may not impact OS or physician-assessed PFS in selected PM-patients., Competing Interests: Disclosures SS: Grants (institutional): AstraZeneca, Janssen, BMS; Advisory boards (institutional): MSD, Merck, BMS; AstraZeneca, Pfizer, Janssen, Roche; Travel support: Takeda, MSD, Amgen and Roche. PB: Advisory Boards: Pfizer, Boehringer Ingelheim, Abbvie, Astra Zeneca (no financial remuneration), Mirati (no financial remuneration), RAPT Therapeutics (no financial remuneration); Honorarium: Merck, Eli Lilly. GL: Advisory (institutional): Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Merck, Takeda, Pfizer, Hoffman La Roche, Abbvie, EMD Serono, Eli Lilly, Novartis, Jazz. Grants(institutional): Takeda, Boehringer Ingelheim, Pfizer, AstraZeneca. All other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM., Methods: An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies., Results: NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice., Conclusions: NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2024 The Authors.)

Malignant mesothelioma, a highly aggressive cancer that primarily affects the serosal membranes, has limited therapeutic options, particularly for cavitary tumors, such as peritoneal and pleural malignant mesothelioma. Intracavitary administration of a radioimmunoconjugate to locally target mesothelioma cancer cells has been proposed as a treatment. CD146, upregulated in mesothelioma but not in healthy tissues, is a promising therapeutic target. This study characterized CD146 expression and binding/internalization kinetics of the CD146-targeting antibody OI-3 coupled with 212 Pb ( 212 Pb-TCMC-OI-3) in human mesothelioma cells. Flow cytometry showed that both chimeric (chOI-3) and murine (mOI-3) antibodies rapidly bound and internalized within 1-6 h in MSTO-211H cells. 212 Pb-TCMC-chOI-3 exhibited 3.1- to 13.7-fold and 3.1- to 8.5-fold increased internalized 212 Pb and 212 Bi atoms per cell at 2 and 24 h, respectively, compared to isotype control, underscoring enhanced internalization efficiency. Intraperitoneal administration of 212 Pb-TCMC-mOI-3 to mice with intraperitoneal MSTO-211H xenografts improved median survival by a ratio of 1.3 compared to non-binding 212 Pb-TCMC-mIgG1. The ability of 212 Pb-TCMC-mOI-3 to target and inhibit the growth of intraperitoneal mesothelioma xenografts supports targeted radionuclide therapy's efficacy for metastatic peritoneal mesothelioma. This study highlights the potential of localized CD146-targeted radioimmunotherapy for malignant mesothelioma, offering a new avenue for improving patient outcomes., (© 2024. The Author(s).)

Diffuse pleural mesothelioma (DPM) is a lethal cancer with a poor prognosis and limited treatment options. The Hippo signaling pathway genes, such as NF2 and LATS1/2, are frequently mutated in DPM, indicating a tumor suppressor role in the development of DPM. Here, we show that in DPM cell lines lacking NF2 and in mice with a conditional Nf2 knockout, downregulation of WWC proteins, another family of Hippo pathway regulators, accelerates DPM progression. Conversely, the expression of SuperHippo, a WWC-derived minigene, effectively enhances Hippo signaling and suppresses DPM development. Moreover, the adeno-associated virus serotype 6 (AAV6) has been engineered to deliver both NF2 and SuperHippo genes into mesothelial cells, which substantially impedes tumor growth in xenograft and genetic DPM models and prolongs the median survival of mice. These findings serve as a proof of concept for the potential use of gene therapy targeting the Hippo pathway to treat DPM., Competing Interests: Declaration of interests A patent application about mesothelioma gene therapy has been filed., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%. Outcomes may vary according to stage at time of diagnosis and histologic subtype. Most recently, clinical trials utilizing dual checkpoint inhibitor regimens and chemotherapy in combination with immune oncologic agents have demonstrated impactful changes in outcomes. In this article, we review studies that have led to the successful implementation of immunotherapy in clinical practice for the treatment of this disease and highlight ongoing clinical trials exploring the use of different immunotherapy strategies for the treatment of pleural mesothelioma. We also discuss the challenges of immunotherapy-based approaches in the context of mesothelioma and future strategies currently being investigated to overcome them.

Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma. At present, the recommended first-line systemic treatment options may include immunotherapy with nivolumab plus ipilimumab or chemotherapy with pemetrexed plus either cisplatin or carboplatin. For second-line treatment, the other previously unchosen first-line option can be used. Off-label bevacizumab may be considered in combination with chemotherapy among carefully selected patients. The benefit of third-line treatment or beyond is less clear. Nonetheless, a number of single-agent regimens show modest activity. Anecdotal reports of children or young adults with peritoneal mesothelioma harboring ALK rearrangement have suggested the efficacy of ALK inhibitors for this rare population. In summary, there is a growing number of systemic therapy options for peritoneal mesothelioma. To gain a better insight into this disease, future prospective trials in mesothelioma should include more patients with peritoneal mesothelioma.

Background: The aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30., Methods: The study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure., Results: Out of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery., Conclusion: Although there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma., (© 2024. The Author(s).)

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of immune checkpoint inhibitors (single-agent or combination therapy) in people with advanced malignant pleural mesothelioma in a first-line or salvage setting., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Malignant peritoneal mesothelioma (MPM) is a rare and invasive tumor, and some patients will develop paraneoplastic syndrome (PS) during the course of the disease. This review summarizes PS associated with MPM, focusing on the clinical characteristics and treatment progress in hematological, endocrine, rheumatic, neurological, urinary, and other systems to decrease missed diagnosis and misdiagnosis, help early diagnosis and prompt treatment, and provide guidance for the clinical decision-making of this kind of patients., (© 2024 Wiley Periodicals LLC.)

Ranked high in worldwide growing health issues, pleural diseases affect approximately one million people globally per year and are often correlated with a poor prognosis. Among these pleural diseases, malignant pleural mesothelioma (PM), a neoplastic disease mainly due to asbestos exposure, still remains a diagnostic challenge. Timely diagnosis is imperative to define the most suitable therapeutic approach for the patient, but the choice of diagnostic modalities depends on operator experience and local facilities while bearing in mind the yield of each diagnostic procedure. Since the analysis of pleural fluid cytology is not sufficient in differentiating historical features in PM, histopathological and morphological features obtained via tissue biopsies are fundamental. The quality of biopsy samples is crucial and often requires highly qualified expertise. Since adequate tissue biopsy is essential, medical or video-assisted thoracoscopy (MT or VATS) is proposed as the most suitable approach, with the former being a physician-led procedure. Indeed, MT is the diagnostic gold standard for malignant pleural pathologies. Moreover, this medical or surgical approach can allow diagnostic and therapeutic procedures: it provides the possibility of video-assisted biopsies, the drainage of high volumes of pleural fluid and the administration of sterile calibrated talcum powder under visual control in order to achieve pleurodesis, placement of indwelling pleural catheters if required and in a near future potential intrapleural therapy. In this context, dedicated diagnostic pathways remain a crucial need, especially to quickly and properly diagnose PM. Lastly, the interdisciplinary approach and multidisciplinary collaboration should always be implemented in order to direct the patient to the best customised diagnostic and therapeutic pathway. At the present time, the diagnosis of PM remains an unsolved problem despite MDT (multidisciplinary team) meetings, mainly because of the lack of standardised diagnostic work-up. This review aims to provide an overview of diagnostic procedures in order to propose a clear strategy.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms' tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8-10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8-10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial's primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer., Competing Interests: This trial is funded by Kom op tegen Kanker, NV Roche SA, the Methusalem financing program of the Flemish Government and the UZA Foundation. For more details, refer to the Financial Disclosure Section. In addition, PG received travel grants and honoraria for speaking or participation at meetings from SA Roche NV. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors have no competing interests to declare., (Copyright: © 2024 Van den Bossche et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Dendritic cell immunotherapy has proven to be safe and induces an immune response in humans. We aimed to establish the efficacy of dendritic cells loaded with allogeneic tumour cell lysate (MesoPher, Amphera BV, 's-Hertogenbosch, Netherlands) as maintenance therapy in patients with pleural mesothelioma., Methods: In this open-label, randomised, phase 2/3 study, patients with histologically confirmed unresectable pleural mesothelioma, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status score of 0-1, and non-progressing disease after four to six cycles of standard chemotherapy (with pemetrexed 500 mg/m 2 plus platinum [cisplatin 75 mg/m 2 or carboplatin area under the curve of 5]) were recruited from four centres in Belgium, France, and The Netherlands. Participants were randomly assigned (1:1), using block randomisation (block size of 4), stratified by centre and histology (epithelioid vs other), to MesoPher treatment plus best supportive care or best supportive care alone. Patients received up to a maximum of five MesoPher infusions, with treatment administered on days 1, 15, and 29, and weeks 18 and 30. At each timepoint, participants received an injection of 25 × 10 6 dendritic cells (two-thirds of the dendritic cells were administered intravenously and a third were injected intradermally). Best supportive care was per local institutional standards. The primary endpoint was overall survival, assessed in all participants randomly assigned to treatment (full analysis set) and safety assessed in all randomly assigned participants, and who underwent leukapheresis if they were in the MesoPher group. This study is registered with ClinicalTrials.gov, NCT03610360, and is closed for accrual., Findings: Between June 21, 2018, and June 10, 2021, 176 patients were screened and randomly assigned to the MesoPher group (n=88) or best supportive care alone group (n=88). One participant in the MesoPher group did not undergo leukapheresis. Mean age was 68 years (SD 8), 149 (85%) of 176 were male, 27 (15%) were female, 173 (98%) were White, two were Asian (1%), and one (1%) was other race. As of data cutoff (June 24, 2023), after a median follow up of 15·1 months (IQR 9·5-22·4), median overall survival was 16·8 months (95% CI 12·4-20·3; 61 [69%] of 88 died) in the MesoPher group and 18·3 months (14·3-21·9; 59 [67%] of 88 died) in the best supportive care group (hazard ratio 1·10 [95% CI 0·77-1·57]; log-rank p=0·62). The most common grade 3-4 treatment-emergent adverse events were chest pain (three [3%] of 87 in the MesoPher group vs two [2%] of 88 in the best supportive care group), dyspnoea (none vs two [2%]), anaemia (two [2%] vs none), nausea (none vs two [2%]), and pneumonia (none vs two [2%]). No deaths due to treatment-emergent adverse events were recorded. Treatment-related adverse events consisted of infusion-related reactions (fever, chills, and fatigue), which occurred in 64 (74%) of 87 patients in the MesoPher group, and injection-site reactions (itch, erythema, and induration), which occurred in 73 (84%) patients, and all were grade 1-2 in severity. No deaths were determined to be treatment related., Interpretation: MesoPher did not show improvement in overall survival in patients with pleural mesothelioma. Immune checkpoint therapy is now standard of care in pleural mesothelioma. Further randomised studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities., Funding: Amphera BV and EU HORIZON., Competing Interests: Declaration of interests JGA reports grants, personal fees, research support, and stock ownership from Amphera and personal fees from Bristol-Myers Squibb, Eli-Lilly, MSD, CureVac, and Novocure. JGA has a patent for a tumour cell lysate licensed, a patent for a combination immunotherapy licensed, and a patent for a biomarker for immunotherapy licensed. RC reports personal fees from Janssen, MSD, Spectrum, and Librerium. PB reports receiving consulting fees for advisorships from AstraZeneca and Bristol Myers Squibb. AS reports personal fees and non-financial support from AstraZeneca, Bristol Myers Squibb, and MSD, of which the principal investigator fees directly went to their institution (CHRU Lille). DF reports personal fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and AstraZeneca; personal fees and travel bursary from RS Oncology; and research funding from Astex Pharmaceuticals, Bergen Bio, Iovance, Owkin, GSK, MSD Oncology, Roche UK, Clovis Oncology, and Aldeyra. KB reports personal fees from Amphera. RK reports that he received fees from Amphera BV for statistical services related to the study. RBer reports personal fees from Boehringer Ingelheim, Otsuka, Amgen, Lilly, GSK, EISAI, and Gilead; grants from Astra Zeneca, Roche, andNovartis; and grants and personal fees from MSD. RM and IE received consulting fees from Amphera BV and are stock owner of Amphera BV. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Mesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review's aims were to identify/synthesise international evidence on mesothelioma's MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness., Design: Systematic review., Data Sources: Databases, searched March 2022 and March 2024, were MEDLINE; CINAHL; PsycINFO; Cochrane Library; ASSIA., Eligibility Criteria: We included study designs focusing on psychological impacts of living with mesothelioma and MHWB interventions used by patients and informal carers, published in English since January 2002., Data Extraction and Synthesis: A team of reviewers screened included studies using standardised methods. Quality was assessed using validated tools: Mixed-Methods Appraisal tool for primary research and Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews., Results: Forty-eight studies met the inclusion criteria: 20 qualitative, 16 quantitative, nine reviews, two mixed-methods, one combined systematic review/qualitative study. UK studies predominated. Many MHWB impacts were reported, including traumatic stress, depression, anxiety and guilt. These were influenced by mesothelioma's causation, communication issues and carer-patient relational interactions. Participants used wide-ranging MHWB interventions, including religious/spiritual practice; talking to mental-health professionals; meaning-making. Some strategies were presented as unhelpful, for example, denial. Participants reported lack of access to support., Conclusions: Most qualitative studies were rated high quality. The quality of the quantitative studies and reviews varied. The sparse literature regarding MHWB in mesothelioma means more research is needed into impacts on patients and carers, including trauma. To enable access to evidence-based support, research is recommended concerning MHWB interventions' effectiveness in mesothelioma., Prospero Registration Number: CRD42022302187., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The surgical treatment of malignant pleural mesothelioma (MPM) involves procedures to achieve macroscopic complete resection, depending on the patient's condition. We reviewed the evolution of surgical approaches for resectable MPM. Since surgery is no more than a single step in the set of processes in multimodality treatment (MMT), we concluded that these procedures should give precedence to lung preservation and minimize resection whenever possible. Postoperative quality of life must be prioritized when the patient can receive appropriate adjuvant therapy., (© 2023. The Author(s).)

Competing Interests: ID-J declares consulting fees from AstraZeneca, Bayer, BostonGene, Bristol Myers Squibb, Catalyst, Eli Lilly, Epi-Q, Genentech, Gilead, Janssen, Merus, Novocure, Pfizer, Roche, Sanofi-Genzyme, Syros, ThermoFisher Scientific, and Xcovery; and honoraria from Foundation Medicine, Creative Education Concepts, OncLive, ASCO Post, DAVA Oncology, Medscape, Research to Practice, Total Health, Aptitude Health, American Lung Association, PeerVIew, and Curio. MGZ declares consulting fees from Roche Diagnostics, Curis, and Ikena; honoraria from Physicians' Education Resource and Medscape; and research funding to Memorial Sloan Kettering Cancer Center from Vivace, MedImmune, Precog, GSK, Epizyme, Polaris, Sellas Life Sciences, Bristol Myers Squibb, Millenium, Curis, and Atara. MGZ also serves as Chair of the Board of Directors of the Mesothelioma Applied Research Foundation, an uncompensated position.

Background: Mesothelioma is a terminal disease that is linked to asbestos exposure. Continuity is difficult for GPs, and other healthcare professionals (HCPs), to provide within the current NHS primary care system, but is highly valued by people with mesothelioma., Aim: To understand the experiences of continuity in primary care among people with mesothelioma, their close persons, and their HCPs; how they achieve this (or not); and how it affects their healthcare service use., Method: Realist case studies of patient journeys through the healthcare system (involving longitudinal interviews with people with mesothelioma, their close persons, and HCPs; and exploration of the organisational context). Data analysis allowed understanding of hidden mechanisms (resources and reasoning), triggered in certain contexts, leading to specific outcomes., Results: Forty-eight interviews (involving 9 patients, 8 close persons, and 12 HCPs) were undertaken (totalling 30.8 hours/1848 minutes). Context-Mechanism-Outcome configurations related to: challenges unique to mesothelioma; capacity of patients/close persons/HCPs to facilitate continuity; multidisciplinary (MDT) approach differs from the family doctor model; and 'the NHS primary care system is broken'., Conclusion: Patients perceive their continuity needs to be unmet by the inflexible primary care system, which needs to adapt to a society in which people receive increasingly novel treatments and live longer with complex healthcare needs. A societal perspective shift is required to understand that an MDT now shares responsibility for care, rather than an individual family doctor. Policy documents continue to focus on access, and still do not advocate strongly enough for continuity, despite unequivocal evidence demonstrating its worth., (© British Journal of General Practice 2024.)

Purpose: Malignant peritoneal and pleural mesothelioma are rare in young patients, with a paucity of data regarding clinical characteristics and outcomes. We aimed to describe the clinical characteristics, treatment strategies, and outcomes for pediatric and adolescent/young adult (AYA) patients., Methods: The National Cancer Database (NCDB) was queried for malignant peritoneal and pleural mesothelioma in pediatric and AYA patients (ages 0-39) from 2004 to 2019. Stratification was performed for pediatric (age 0-21) and young adult (age 22-39) patients. Chi-squared, multivariable cox regression, and Kaplan-Meier analyses were performed., Results: We identified 570 total patients, 46 pediatric and 524 young adult, with mesothelioma (363 peritoneal and 207 pleural). There were significant differences in sex distribution as patients with peritoneal mesothelioma were more frequently female (63.1%). Patients with peritoneal mesothelioma were more likely to have radical surgery compared to pleural mesothelioma (56.7% v. 24.6%, respectively). A majority of patients with peritoneal and pleural mesothelioma received chemotherapy (66.4% and 61.4%, respectively). For peritoneal mesothelioma, surgical resection was associated with improved overall survival, whereas male sex, neoadjuvant chemotherapy, and radiation were associated with worse overall survival. For pleural mesothelioma, intraoperative chemotherapy was associated with improved overall survival, whereas Black race was associated with worse overall survival. Mean overall survival was greater for patients with peritoneal mesothelioma (125 months) compared to those with pleural mesothelioma (69 months), which remained significant after stratification of pediatric and young adult patients., Conclusion: By analyzing a large cohort of pediatric and AYA mesothelioma, this study highlights clinical, prognostic, and survival differences between peritoneal and pleural disease., Level of Evidence: Level III., Type of Study: Retrospective., Competing Interests: Conflicts of interest The authors have no related conflicts of interest to declare. The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies., Competing Interests: Declaration of interests KGB declares institutional grant funding from Rocket Medical and RS Oncology; lecture honoraria from Bristol-Myers Squibb; and the role of chief investigator of the PREDICT-Meso International Accelerator Network. PSA declares research funding from ATARA Biotherapeutics; patents, royalties, and intellectual property on therapies licensed to ATARA Biotherapeutics; and scientific advisory board membership and consulting fees from ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion Pharma, and Outpace Bio. PA declares equipment loans for courses from Novatech, Wolf, and Olympus. LD declares lecture honoraria from Bristol-Myers Squibb. YCGL declares receipt of equipment from Rocket Medical for use in clinical trials. ASM declares institutional grant funding from Novartis and Verily; consulting fees from Rising Tide and TRIPTYCH Health Partners; institutional payments or honoraria from Janssen, BeiGene, Chugai Pharmaceutical (Roche), Ideology Health (formerly Health Media), Antoni van Leeuwenhoek Kanker Instituut, AXIS Medical Education, Johnson & Johnson Global Services, Intellisphere, Answers in CME, University of Miami International Mesothelioma Symposium, and Immunocore; support for attending meetings from Shanghai Roche; membership of scientific advisory boards for AbbVie, AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Takeda Oncology, and Sanofi Genzyme; and study funding from Bristol-Myers Squibb. SJM is co-principal investigator of the Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration in Targeted Delivery for Hard-to-Treat Cancers; he declares consulting fees from DefiniGEN, and support for attending meetings from Alpha-1 Foundation, Federation of American Societies for Experimental Biology, and Mesothelioma UK. NM declares consulting fees from Rocket Medical UK, Cook Medical UK, and Becton Dickinson. VP declares grant funding from the Danish Comprehensive Cancer Center and no conflicts of interest within the scope of this Viewpoint. NMR declares consulting fees from Rocket Medical UK, Cook Medical UK, and LTI USA. MGZ declares institutional grant funding from Medimmune, Precog, GSK, Epizyme, Polaris, Sellas Life Sciences, Bristol-Myers Squibb, Millenium, Curis, and Atara; consulting fees from Curis, Ikena, Takeda, GSK, and Novocure; and honoraria from PER and Medscape. DS declares support including research funding and consulting fees from AstraZeneca, Boehringer Ingelheim, Exigo Management, Flame Biosciences, HitchBio, Intuitive Surgical, Janssen, Johnson & Johnson, Medscape, Olympus Corporation of the Americas (also known as Spiration), Sensei Biotherapeutics, Trizell, Trustees of the University of Pennsylvania, Verismo, and Wolters Kluwer Health. DAF declares institutional grants from Aldeyra, Astex Therapeutics, Bayer Oncology, Bergen Bio, Boehringer Ingelheim, Clovis Oncology, Eli Lilly, Lovance, MSD, Owkin, Roche Oncology, and RS Oncology; consulting fees from Cambridge Clinical Laboratories and RS Oncology; honoraria from MSD and Bristol-Myers Squibb; support for attending meetings from RS Oncology; and participation on data monitoring or advisory boards for AstraZeneca and RS Oncology. TP declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent., Design: A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period., Setting: Secondary thoracic cancer care., Results: Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment., Conclusions: With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible., Trial Registration Number: ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The current treatment for mesothelioma, in selected cases, consists of extended pleurodecortication and intrathoracic hyperthermic chemotherapy. This technique is laborious and detailed and must be followed step by step to achieve good results. We present the case of a patient with epithelioid mesothelioma meeting surgical criteria who underwent the mentioned technique, experiencing an adequate postoperative period and an early discharge. This experience demonstrates that the technique is safe when performed in centres with experience and the means to address this complex pathology., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Rationale: Malignant peritoneal mesothelioma (MPM) is a rare clinical disease. Although there are several reports describing intraperitoneal mesothelioma of the lung, liver, and intestine, retroperitoneal mesothelioma is, to our knowledge, very rare and rarely reported. In recent years, our best clinical protocols for the treatment and diagnosis of retroperitoneal mesothelioma have not been proven and the diagnosis and treatment are challenging., Patient Concerns: A 37-year-old Chinese woman complained of bilateral low back pain for a month, with obvious symptoms of low back pain on the left side. To treat low back pain, retroperitoneal masses were found during physical examination. The patient consulted a urological specialist for further treatment., Diagnosis: After the operation, pathological biopsy confirmed retroperitoneal epithelioid diffuse mesothelioma., Interventions: After exclusion of surgical contraindications, the patient underwent laparoscopic retroperitoneal lesion resection under tracheal intubation and general anesthesia, and the operation was successful., Outcomes: On the tenth day after surgery, the patient vital signs were stable, and he was discharged., Lessons: Patients with malignant peritoneal mesothelioma may have no typical clinical symptoms, and the diagnosis is based on pathological and immunohistochemical examination. In selected patients, surgical cell reduction and intraoperative intraperitoneal heat chemotherapy have become the first choice of treatment, which can achieve ideal therapeutic effects and prolong survival., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background Aims: Several anti-mesothelin (MSLN) chimeric antigen receptor (CAR) T cells are in phase 1/2 clinical trials to treat solid-organ malignancies. The effect of MSLN antigen density on MSLN CAR cytotoxicity against tumor cells has not been examined previously, nor are there data regarding the effect of agents that increase MSLN antigen density on anti-MSLN CAR T cell efficacy., Methods: MSLN antigen density was measured on a panel of pancreatic cancer and mesothelioma cell lines by flow cytometry. In parallel, the cytotoxicity and specificity of two anti-MSLN CAR T cells (m912 and SS1) were compared against these cell lines using a real-time impedance-based assay. The effect of two MSLN 'sheddase' inhibitors (lanabecestat and TMI-1) that increase MSLN surface expression was also tested in combination with CAR T cells., Results: SS1 CAR T cells were more cytotoxic compared with m912 CAR T cells against cell lines that expressed fewer than ∼170 000 MSLN molecules/cell. A comparison of the m912 and amatuximab (humanized SS1) antibodies identified that amatuximab could detect and bind to lower levels of MSLN on pancreatic cancer and mesothelioma cell lines, suggesting that superior antibody/scFv affinity was the reason for the SS1 CAR's superior cytotoxicity. The cytotoxicity of m912 CAR T cells was improved in the presence of sheddase inhibitors, which increased MSLN antigen density., Conclusions: These data highlight the value of assessing CAR constructs against a panel of cells expressing varying degrees of target tumor antigen as occurs in human tumors. Furthermore, the problem of low antigen density may be overcome by concomitant administration of drugs that inhibit enzymatic shedding of MSLN., Competing Interests: Declaration of competing interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article. JEJR reports advisory roles for Gene Technology Technical Advisory Committee, Office of the Gene Technology Regulator, Australian Government; and Human Research Ethics Committee, Genea. JEJR also reports honoraria speaker fees or advisory roles for Gilead, Roche, Novartis, Bluebird Bio, SPARK Therapeutics, Cynata, and Pfizer Inc.; Woke Pharmaceutical (non-executive director); Kennerton Capital (non-executive director); AAVec Bio (co-founder); consultant role for Rarecyte (stocks in lieu)., (Copyright © 2024. Published by Elsevier Inc.)

Despite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable at approximately 2500 cases annually. This trend is not unique to the United States but is also a global phenomenon, associated with increased aging of populations worldwide. Although geoeconomic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging. Recognizing that mesothelioma shares genetic instability and immune system effects with other age-related cancers is crucial because the impact of aging on mesothelioma is frequently assessed in the context of disease latency after asbestos exposure. Nevertheless, the long latency period, often cited as a reason for mesothelioma's elderly predominance, should not overshadow the shared mechanisms. This communication focuses on the role of immune surveillance in mesothelioma, particularly exploring the impact of immune escape resulting from altered TSG function during aging, contributing to the phylogenetic development of gene mutations and mesothelioma oncogenesis. The interplay between the immune system, TSGs, and aging not only shapes the immune landscape in mesothelioma but also contributes to the development of heterogeneous tumor microenvironments, significantly influencing responses to immunotherapy approaches and survival rates. By understanding the complex interplay between aging, TSG decline, and immune senescence, health care professionals can pave the way for more effective and personalized immunotherapies, ultimately offering hope for better outcomes in the fight against mesothelioma., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor-associated antigens (TAAs) that might induce an anti-tumor immunity. Due to their immunostimulatory effect, OVs have been explored for cancer vaccination against specific TAAs. However, this approach usually requires genetic modification of the virus and the production of a new viral vector for each target, which is difficult to implement for low prevalent antigens. In a recent study, Chiaro et al. presented an elegant proof of concept on how to implement the PeptiCRAd vaccination platform to overcome this limitation for the treatment of mesothelioma. Authors showed the feasibility of identifying immunogenic TAAs in human mesothelioma and using them to coat oncolytic adenovirus particles. The result was a customized virus-based cancer vaccine that circumvents time and resource-consuming steps incurred from genetically engineering viruses. Although some questions remain to be addressed, this interesting approach suggests novel strategies for personalized cancer medicine using oncolytic virotherapy., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Malignant pleural mesothelioma is a rare, aggressive, and incurable cancer with a poor prognosis and high symptom burden. For these patients, little is known about the impact of palliative care consultation on outcomes such as mortality, hospital admissions, or emergency department visits. The aim of this study is to determine if referral to supportive and palliative care in patients with malignant pleural mesothelioma is associated with survival and decreased hospital admissions and emergency department visits. This is a retrospective chart review. Study participants include all malignant pleural mesothelioma patients seen at The Ottawa Hospital-an acute care tertiary center-between January 2002 and March 2019. In total, 223 patients were included in the study. The mean age at diagnosis was 72.4 years and 82.5% were male. Of the patients diagnosed between 2002 and 2010, only 11 (9.6%) were referred to palliative care. By comparison, of those diagnosed between 2011 and 2019, 49 (45.4%) were referred to palliative care. Median time from diagnosis to referral was 4.1 months. There was no significant difference in the median survival of patients referred for palliative care compared to those who did not receive palliative care ( p = 0.46). We found no association between receiving palliative care and the mean number of hospital admissions (1.04 vs. 0.91) from diagnosis to death, and an increase in mean number of emergency department visits in the palliative care group (2.30 vs. 1.18). Although there was increased utilization of palliative care services, more than half of the MPM patients did not receive palliative care despite their limited survival. There was an increase in emergency department visits in the palliative care group; this may represent an increase in the symptom burden (i.e., indication bias) in those referred to palliative care.

Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Competing Interests: Declaration of competing interest I have no competing interests, whether financial or non-financial, that could compromise the objectivity, integrity, or impartiality of the research conducted or the findings reported in this paper.