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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.)

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.)

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).)

Background: Primary intrahepatic mesothelioma (PIHMM) has been rarely reported. Its typical clinical presentation, radiological features and pathology have not been defined. Here, we aimed to summarize its diagnosis and treatment., Methods: We conducted a retrospective analysis of three cases of PIHMM in the First Affiliated Hospital of Zhejiang University School of Medicine and reviewed the current literature to investigate the clinical and pathological characteristics and prognosis of PIHMM., Results: Based on our case series and the literature, the mean age of PIHMM was 59.7 (41-83) years. Most patients present with nonspecific symptoms such as abdominal pain, fever, weight loss and weakness. On imaging, PIHMM usually presented as a solid, heterogeneous soft tissue mass with irregular margins and significant enhancement of the margins in the arterial phase. Immunohistochemical markers such as calretinin, cytokeratin (CK)5/6, D2-40, WT-1, mesothelin CK and vimentin may be useful for diagnosis. The 3-year relapse-free survival rate (RFS) was 51.85%, the 3-year overall survival (OS) rate was 83.33% and the 3-year postoperative overall survival rate was 100%., Conclusion: PIHMM can only be diagnosed by careful postoperative pathology, because of its nonspecific clinical presentations, serological indicators or imaging features. Immunohistochemical staining is very useful to distinguish this tumor from other liver tumors. Surgery is the mainstay of treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

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.)

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.)

Malignant Mesothelioma (MM) has a striking impact on the somatopsychic balance of patients and their families, including physical, psychological, and interpersonal problems. The aim of this systematic literature review was to investigate what psychological interventions are offered to patients with MM and their caregivers worldwide., Methods: The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The literature search led to the identification of 12 articles. Results were categorized into five categories. 1. Individual psychological support, 2. Group psychological support, 3. Cognitive-behavioral group psychotherapy, 4. Brief psychoanalytic groups, 5. Multifamily group., Results: The interventions differed in terms of form, duration and resources used. Most of them were group-based and psychoanalytically oriented, although individual and cognitive-behavioral interventions were also described. Despite the differences, the interventions appeared to be fundamental in facilitating the processing of mental pain and anger related to the diagnosis., Conclusion: Our study has shown that there are still few psychological interventions available for MM patients and their caregivers. The somatopsychic consequences of MM in patients and caregivers should encourage institutions and healthcare professionals to develop assessment and intervention models that address the different dimensions of their suffering and promote their residual vitality., Competing Interests: Conflict of Interest Statement All authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Malignant peritoneal mesothelioma (MPeM) is a rare primary malignant tumor originating from peritoneal mesothelial cells. Insufficient specificity of the symptoms and their frequent reappearance following surgery make it challenging to diagnose, creating a need for more efficient treatment options. Natural killer cells (NK cells) are part of the innate immune system and are classified as lymphoid cells. Under the regulation of activating and inhibiting receptors, NK cells secrete various cytokines to exert cytotoxic effects and participate in antiforeign body, antiviral, and antitumor activities. This review provides a comprehensive summary of the specific alterations observed in NK cells following MPeM treatment, including changes in cell number, subpopulation distribution, active receptors, and cytotoxicity. In addition, we summarize the impact of various therapeutic interventions, such as chemotherapy, immunotherapy, and targeted therapy, on NK cell function post-MPeM treatment.

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.)

Background: Obesity is a public health concern with an increasing occurrence worldwide. Literature regarding impact of obesity on results after management of peritoneal carcinomatosis is poor. Our aim was to compare postoperative and oncological outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies according to the body mass index., Methods: All the patients managed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies (including mainly pseudomyxoma peritonei and peritoneal mesothelioma), between 1995 and 2020, were retrospectively included from the French national registry of rare peritoneal tumors., Results: 1450 patients were retrospectively included (63.5 % female, mean age 54 ± 13 years). Patients were divided into two groups according to their body mass index: non-obese (n = 1248, 86 %) and obese (n = 202, 14 %). Overall morbidity was significantly lower in non-obese patients in comparison with obese patients (n = 532/1248, 43 % vs n = 106/202, 53 %, p = 0.009). Medical and surgical morbidities were significantly lower in non-obese patients in comparison with obese patients (423/1258, 34 % vs n = 86/202, 43 %, p = 0.02 and n = 321/1248, 26 % vs n = 67/202, 33 %, p = 0.003, respectively). One-, 5- and 10-year overall survivals were similar between non-obese and obese patients (95 %, 82 % and 70 % vs 94 %, 76 % and 63 %; p = 0.1). One-, 5- and 10-year disease free survivals were similar between non-obese and obese patients (84 %, 67 % and 61 % vs 79 %, 62 % and 56 %, p = 0.1)., Conclusion: Obese patients have to be carefully managed after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies. Some perioperative prophylactic treatments could be specifically implemented to reduce thromboembolic events, metabolic and wound complications., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: This study aimed to evaluate the demographic," clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population., Methods: A retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients' diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study., Results: The study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason., Conclusions: According to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable., (© 2024. The Author(s).)

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.

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments., Methods: This historical cohort study based on routinely collected Danish National Registry data included adults newly diagnosed with MPM between 01 January 2011 and 31 May 2018. Summary statistics were used to describe patient characteristics and initial treatment. OS was estimated using Kaplan-Meier methods; Cox regression was used to compare patient mortality against the (age/sex-matched) general population and to investigate mortality predictors., Results: Overall, 880 patients were included; 44% had advanced MPM, 37% had non-advanced MPM, and 19% had unknown MPM stage. Median age at diagnosis was 71.9 years, and 82% of the patients were male. Within 180 days of diagnosis, no treatment was recorded for 215 patients (54%) with advanced MPM and 150 (46%) with non-advanced MPM. Median time-to-initial treatment (interquartile range) was 47 days (31-111) overall, 40 days (28-77) in patients with advanced MPM, and 53 days (35-121) with non-advanced MPM. Median OS was 13.7 months overall (non-advanced MPM: 18.0 months vs. advanced MPM: 10.0 months). Predictors of higher mortality were older age at diagnosis, histology, and advanced MPM stage., Interpretation: These findings provide a baseline upon which to evaluate MPM epidemiology as newer treatments are adopted in routine practice.

Introduction: Malign peritoneal mesothelioma (MPM) is an uncommon disease that is difficult to treat. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are the gold standards for treating MPM. Sometimes extreme cytoreductive surgery (eCRS) is required to achieve complete cytoreduction, which is one of the most important prognostic factors. There is limited information in the literature about the contribution of eCRS in patients with MPM. In this study, we aimed to investigate the impact of eCRS on survival and perioperative outcomes., Methods: The Department of Surgical Oncology at Cumhuriyet University database was retrospectively reviewed for MPM patients who underwent CRS-HIPEC between January 2004 and December 2018. Patients who underwent CRS-HIPEC were divided into eCRS and less extensive CRS (leCRS) groups. A resection of ≥ 5 organs or ≥ 3 small bowel anastomoses were defined as eCRS. Both groups were compared regarding survival, demographic information, and perioperative outcomes., Results: A total of 31 patients were included. eCRS-HIPEC was used in 15 patients. Complete cytoreduction (CC score 0/1) was achieved in all 31 patients. Compared to leCRS, the eCRS group had a longer median length of stay, longer intensive care unit stay, a higher median peritoneal cancer index (PCI), higher intraoperative blood loss, more frequent occurrence of any complication, and a longer operative time (all p values < 0.001). Clavien Dindo 3-4 complications, ASA, and gender were similar in both groups of patients ( p  > 0.05). It was found that there was no significant difference between the OS of the eCRS and leCRS groups (37.5 vs. 42.8 months, p  = 0.895)., Conclusions: Rates of serious complications and morbidity are similar in patients undergoing eCRS compared to leCRS. In patients with high PCI and multiorgan involvement, complete cytoreduction can be achieved by performing eCRS, and survival results equivalent to those with low PCI can be achieved.

Attenuated measles virus (MV) exerts its oncolytic activity in malignant pleural mesothelioma (MPM) cells that lack type-I interferon (IFN-I) production or responsiveness. However, other cells in the tumor microenvironment (TME), such as myeloid cells, possess functional antiviral pathways. In this study, we aimed to characterize the interplay between MV and the myeloid cells in human MPM. We cocultured MPM cell lines with monocytes or macrophages and infected them with MV. We analyzed the transcriptome of each cell type and studied their secretion and phenotypes by high-dimensional flow cytometry. We also measured transgene expression using an MV encoding GFP (MV-GFP). We show that MPM cells drive the differentiation of monocytes into M2-like macrophages. These macrophages inhibit GFP expression in tumor cells harboring a defect in IFN-I production and a functional signaling downstream of the IFN-I receptor, while having minimal effects on GFP expression in tumor cells with defect of responsiveness to IFN-I. Interestingly, inhibition of the IFN-I signaling by ruxolitinib restores GFP expression in tumor cells. Upon MV infection, cocultured macrophages express antiviral pro-inflammatory genes and induce the expression of IFN-stimulated genes in tumor cells. MV also increases the expression of HLA and costimulatory molecules on macrophages and their phagocytic activity. Finally, MV induces the secretion of inflammatory cytokines, especially IFN-I, and PD-L1 expression in tumor cells and macrophages. These results show that macrophages reduce viral proteins expression in some MPM cell lines through their IFN-I production and generate a pro-inflammatory interplay that may stimulate the patient's anti-tumor immune response., Competing Interests: FT and JFF are authors of patents on MV. FT owns equity in Oncovita, an oncolytic virotherapy company., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Mesothelioma of the testicular vagina is a rare malignant tumour, most often discovered by chance. The rarity of this type of tumour has not led to the development of specific guidelines. Median survival is estimated at 30 months. The lack of data and official recommendations makes surgical and medical management and follow-up difficult. Men who have not undergone radical orchiectomy die very rapidly after diagnosis. The remission rate at 1 year post-orchidectomy is 47 %, the recurrence rate at 1 year is 53 % and 92 % of relapses occur within 5 years post-operatively. The treatment option of hemiscrotectomy in the first instance has rarely been used; a second-look resection with negative margins may be proposed. The usefulness of adjuvant chemotherapy and/or radiotherapy has not been clearly demonstrated. Local recurrence is accompanied by metastasis in 85 % of cases. In the case of metastatic cancer (15 %), the retro-peritoneal, inguinal and iliac lymph nodes may be invaded. Follow-up by injected thoraco-abdomino-pelvic CT scan is recommended every 3 months for 2 years, then once a year for 3 years, for a total of 5 years of close follow-up. The long-term recurrence rate is 3 %.

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.)

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.

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).)

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.)

Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy.
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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.)

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.)

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.

Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high-risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow-up., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer that has a poor prognosis. An earlier population-based study found that the majority of Dutch patients do not receive anti-cancer treatment. In 2015, Dutch Malignant Mesothelioma care was centralized in two expert centers. We reviewed treatment patterns at these centers, to assess the impact of centralization of MPM care in the Netherlands., Methods: Data from all patients referred to the Dutch MPM expert centers from 2014 to 2020, were retrospectively collected. Descriptive statistics regarding referrals, patient and tumor characteristics, and treatment patterns were provided. Population-based incidence rates were provided by the Netherlands Cancer Registry., Results: From 2014 to 2020, 78 patients were referred to the Dutch Mesothelioma expert centers, of whom 32 were female (41%). From 2014 to 2017, 27 patients were referred, whereas 51 patients were referred from 2018 to 2020. This represents about 24% and 61% of the estimated population incidence, respectively. Treatment patterns were comparable between both periods. Between 2014 and 2018, 33% of patients underwent surgery, 44% systemic therapy, and 22% received best supportive care (BSC), while this was 29%, 37%, and 33% respectively from 2018 to 2020., Conclusion: Centralization of care for patients with MPM resulted in an increase of annual referrals to the Dutch mesothelioma expert centers. While population-based incidence did not change during the study period, the absolute number of patients receiving treatment at our centers did increase. This might be considered a first important step towards better treatment for patients with this fatal disease., Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JB reports reimbursements for his institution (Netherlands Cancer Institute) outside the submitted work from Roche, AstraZeneca and Boehringer Ingelheim. JA reports grants outside the submitted work from Amphera and Roche, ownership interest (including patents) from Amphera, and advisory roles for Amphera, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, MSD and Roche, outside the submitted work. All other authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Malignant mesothelioma is a rare disease with limited treatment options. In malignant pleural mesothelioma (MPM), radical trimodality approaches, including surgery, radiotherapy and systemic chemo- and immunotherapy, have been delivered in some countries but remain controversial due to a lack of randomised evidence. Even in the unresectable scenario, surgery and radiotherapy play an important role in managing pleural effusions and pain, which may optimise wellbeing and maintain performance status. From the systemic treatment point of view, the recent incorporation of anti-angiogenics and, more importantly, immunotherapy has changed the standard of care in a space where chemotherapy with platinum and pemetrexed was the only therapeutic intervention with demonstrated benefits in overall survival. Histology is essential in determining an initial treatment plan as non-epithelioid MPMs may have a higher substantial survival improvement with dual immunotherapy compared with chemotherapy, whereas chemotherapy remains an option for epithelioid MPM; however, predictive biomarkers for systemic therapy are not entirely validated to guide the selection, as a subgroup of MPM patients might not benefit from immunotherapy. This overview approaches how the overall management of mesothelioma is evolving to incorporate the recent changes in the standards of care., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Thomas E. StinchcombeThis author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Genentech/Roche, Foundation Medicine, EMD Serono, Novartis, Daiichi Sankyo, Lilly, Medtronic, Puma Biotechnology, Janssen Oncology, Regeneron, Turning Point Therapeutics, Sanofi/Aventis, GlaxoSmithKlineResearch Funding: AstraZeneca (Inst), Takeda (Inst), Advaxis (Inst), Regeneron (Inst), Seattle Genetics (Inst), Mirati Therapeutics (Inst) Jeffrey BradleyHonoraria: AstraZeneca/MedImmune, Mevion Medical SystemsConsulting or Advisory Role: Varian Medical Systems, GenentechNo other potential conflicts of interest were reported.

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease., Competing Interests: Anne S. TsaoConsulting or Advisory Role: Novartis, Boehringer Ingelheim, Genentech/Roche, Lilly, Bristol Myers Squibb, Epizyme, AstraZeneca/MedImmune, ARIAD, EMD Serono, Takeda, HERONResearch Funding: Merck, Genentech/Roche, Seattle Genetics, Millennium, Bristol Myers Squibb, Boehringer Ingelheim, Polaris, EMD Serono, Seattle Genetics, Takeda, UpToDate Harvey I. PassHonoraria: Genentech/RocheConsulting or Advisory Role: Genentech/Roche, NovartisResearch Funding: Biodesix, Micronoma, NanoString Technologies, Celsius TherapeuticsPatents, Royalties, Other Intellectual Property: Patent Pending, use of fibulin for the diagnosis of mesothelioma; Patent Pending, use of HMGB1 for the diagnosis of mesothelioma, with University of Hawaii; Patent Pending, use of osteopontin for the diagnosis of mesothelioma, with Wayne State UniversityTravel, Accommodations, Expenses: Genentech/Roche Andreas RimnerHonoraria: More HealthConsulting or Advisory Role: AstraZeneca, Merck, Boehringer Ingelheim, Cybrexa TherapeuticsResearch Funding: Varian Medical Systems, Boehringer Ingelheim, Pfizer, AstraZeneca, MerckTravel, Accommodations, Expenses: Philips/Elekta Aaron S. MansfieldHonoraria: Shanghai RocheConsulting or Advisory Role: Genentech, Bristol Myers Squibb, AbbVie, AstraZenecaResearch Funding: NovartisTravel, Accommodations, Expenses: Roche, AbbVieNo other potential conflicts of interest were reported.

Background: Overall survival (OS) for malignant pleural mesothelioma (MPM) in vulnerable subgroups remains poorly understood with scarce data available to guide treatment decisions. The study describes real-world detailed treatment patterns and outcomes of patients with advanced MPM overall and specifically in elderly and poor performance status (PS) patients., Methods: Retrospective chart review was performed for all patients with histologically confirmed MPM seen at University Health Network/Princess Margaret Cancer Centre (UHN-PM)., Results: A total of 667 patients with MPM were identified and 304 advanced-disease MPM (aMPM) patients had continuing care at UHN-PM (UP-cohort). In the UP-cohort, 77% of patients received ≥ one line of systemic treatment. Systemic therapy trial participation was 39%. Patients not treated with systemic therapy (29%) were more likely to be ≥ 75 years and PS ≥ 2. Median OS was 15.3 months (95%CI 13.6-18.3), with longer survival in treated vs. untreated patients (17.4 vs. 10.6 months; P = .01). Longer survival with systemic treatment was seen in patients ≥75 years (12.7 vs. 6.6 months) and patients with poor PS (9.1 vs. 5.9 months). Median progression-free-survival (PFS) and OS for patients treated with second-line therapy was poor (3.0 and 8.9 months, respectively)., Discussion: In our real-world analysis of patients with aMPM treated at an academic referral centre, systemic treatment was given to the majority of patients and benefit was seen even in the elderly and poor PS patients frequently underrepresented in clinical trials. Trial participation was potentially facilitated by the formation of a dedicated multidisciplinary MPM clinic., Competing Interests: Disclosure Sabine Schmid: Advisory (institutional): Boehringer Ingelheim, MSD, BMS; Research grants (institutional): BMS, Astra Zeneca; Travel support: Takeda, Boehringer Ingelheim, MSD Adrian Sacher: Consulting, Advisory Boards: Amgen, AstraZeneca, Bayer, Genentech-Roche, BMS, KisoJi; Honoraria & Sponsored CME/Symposia: Amgen, AstraZeneca, Merck, Genentech-Roche, Bayer, BMS, Pfizer, Tesaro, KisoJi, Iovance, Galvanize Therapeutics; Sponsored Research: AstraZeneca, Genentech imCORE Marc de Perrot: Speaker's bureau: Bayer; Advisory Board: AstraZeneca, Actelion Penelope Bradbury: Financial- Honoraria: Merck; Advisory Board: Boehringer Ingelheim; Advisory Boards without financial remuneration: Abbvie, BMS, AstraZeneca Geoffrey Liu: Honoraria/Advisory: AstraZeneca, Pfizer, Takeda, Novartis, Abbvie, Bayer, Roche; Speaker's bureau: AstraZeneca, Takeda, EMD Serono; Grants (to institution): AstraZeneca, Takeda, Boehringer Ingerheim. None for LZ, KD, KK, MC, MH, DP, FZ, NL, RF, FS, LD, JC, (Copyright © 2021 Elsevier Inc. All rights reserved.)

ATF1, CREB1, and CREM, which encode the CREB family of transcription factors, are fused with EWSR1 or FUS in human neoplasms, such as angiomatoid fibrous histiocytoma. EWSR1/FUS-CREB fusions have recently been reported in a group of malignant epithelioid tumors with a predilection to the peritoneal cavity and frequent cytokeratin expression. Here, we studied 8 cytokeratin-positive abdominal malignancies with these fusions for further characterization. The tumors affected males (15 to 76 y old) and presented as intra-abdominal masses with concurrent or subsequent peritoneal dissemination, ascites, and/or metastases to the liver or lymph nodes. Four patients died of the disease within 18 to 140 months. Cases 1 to 5 showed multinodular growth of monomorphic epithelioid cells with focal serous cysts. Lymphoplasmacytic infiltration was prominent and was associated with systemic inflammatory symptoms. Two patients suffered from membranous nephropathy with nephrosis. The tumors displayed partly overlapping phenotypes with malignant mesothelioma, including diffuse strong expression of AE1/AE3 and WT1 and membranous positivity of sialylated HEG1, although calretinin was negative. Case 6 showed similar histology to cases 1 to 5, but expressed smooth muscle actin diffusely, lacked WT1 and HEG1, and harbored prominent pseudoangiomatous spaces. Cases 7 and 8 displayed dense growth of small oval to short spindle cells, with occasional molding and minor swirling, superficially resembling small cell carcinoma. Lymphoplasmacytic infiltration was not observed. The tumors were positive for AE1/AE3 and CD34 (focal), whereas calretinin, WT1, and HEG1 were negative. The detected fusions were FUS-CREM (n=4), EWSR1-ATF1 (n=2), EWSR1-CREB1 (n=1), and EWSR1-CREM (n=1). We confirmed the prior observation that these tumors do not fit perfectly with known entities and provided additional novel clinicopathologic information. The tumors require wider recognition because of more aggressive behavior than angiomatoid fibrous histiocytoma despite similar genetics, and potential misdiagnosis as unrelated diseases, such as neuroendocrine neoplasms., Competing Interests: Conflicts of Interest and Source of Funding: Supported in part by JSPS Grant-in-Aid for Young Scientists 18K15108 (A.Y.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.

Malignant pleural effusion is common in mesothelioma. We report a case of viscous recurrent malignant mesothelioma pleural effusion. The viscosity was due to the presence of hyaluronic acid and resulted in prolonged drainage time. The use of intrapleural hyaluronidase significantly reduced fluid viscosity and drainage duration. No adverse reactions were noted. This novel case highlights the feasibility and safety of the use of intrapleural hyaluronidase in the management of hyaluronic acid-rich viscous malignant pleural effusion., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Malignant pleural effusion (MPE) is common in malignant pleural mesothelioma (MPM). The survival of patients with MPM and MPE is heterogeneous. The LENT and BRIMS scores using routine clinical parameters were developed to predict the survival of patients with unselected MPE and MPM, respectively. This study aimed to stratify the survival of selected MPM patients with MPE., Methods: Data were collected from subjects diagnosed with MPM and MPE. The LENT and BRIMS scores were applied using a combination of clinical variables to stratify subjects and compare survival characteristics., Results: In total, 101 patients with MPM complicated by MPE were included in the study. The median follow-up time was 71 months (interquartile range: 24-121 months). Overall median survival was 24 (interquartile range: 12-52 months). Based on the LENT score, the low-, moderate-, and high-risk groups accounted for 65.3% (66 cases), 34.7% (35 cases), and 0%, respectively. The cumulative survival rates of the two groups were statistically significant (p = 0.031). The area under the curve (AUC) of the LENT score was 0.662. Based on the BRIMS score, the first, second, third, and fourth risk groups accounted for 1.0% (1 case), 42.9% (35 cases), 28.7% (29 cases), and 19.4% (36 cases), respectively. Survival was significantly higher in patients in the risk groups 1 and 2 than in patients in the risk groups 3 and 4 (p  = 0.037). The AUC of the BRIMS score was 0.605., Conclusions: Using routinely available clinical variables, both LENT and BRIMS scores could stratify selected MPM and MPE patients into risk groups with statistically different survival., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.

Case Presentation: A 57-year-old man with history of stage IIIB right-sided malignant pleural mesothelioma was admitted from his oncologist's office for progressive dyspnea of two weeks duration. He had associated dyspnea at rest and a new dry cough. He denied sputum production, hemoptysis, or fevers, but he did endorse chills, fatigue, and weight loss. The patient was a veteran of the Navy and had extensive international travel in his 20s. He had never been incarcerated and denied any sick contacts or recent travels. He had received a diagnosis of mesothelioma 11 months earlier after presenting to his physician's office with complaints of shortness of breath on exertion. Initial imaging revealed a large right-sided pleural effusion with irregular pleural thickening. He underwent right-sided thoracoscopy, and the pleural biopsy result was consistent with epithelioid mesothelioma. Because of invasion of his seventh rib, he was not a candidate for surgery and underwent palliative radiation and chemotherapy with cisplatin, pemetrexed, and bevacizumab. He was undergoing his eighth cycle of chemotherapy at the time of presentation., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. A recently described nuclear-grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The present study was undertaken to validate this grading system in epithelioid malignant peritoneal mesothelioma (EMPM) and to compare to combined grade, including nuclear atypia, mitotic count, and tumor necrosis. Cases of EMPM, from 1995 to 2018, were analyzed from 7 French institutions from RENAPE network. Solid growth, tumor necrosis, nuclear atypia, and mitotic count were evaluated by at least 3 pathologists from the RENAPATH group. The predictions in terms of OS and PFS of nuclear grade and combined grade were analyzed. Nuclear grade was computed combining nuclear atypia score and mitotic count into a grade of I-III. Another system combining nuclear atypia score, mitotic score, and tumor necrosis was evaluated and defined as a combined grade I-III. A total of 138 cases were identified. The median follow-up was 38.9 months (range: 1.1-196.6). Nuclear and combined grades III were independently associated with a shorter OS (p < 0.05), and a shorter PFS (p < 0.05). Patients with combined grade I tumors had the best overall and progression-free survivals, in comparison to nuclear grade I. In this large multicentric study, combined grade and nuclear grade were the best independent predictors of OS and PFS in EMPM. These systems should be easily described by pathologists involved into the management of malignant peritoneal mesothelioma, because of their potential therapeutic implications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)