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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. 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/m2 plus platinum [cisplatin 75 mg/m2 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 × 106 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. 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. 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. Amphera BV and EU HORIZON. [ABSTRACT FROM AUTHOR]

Pulmonary pathologists often must make a diagnosis based on small specimens derived from aspirated or solid tissue fragments, extracted under radiological guidance, containing limited diagnostic material. This poses a diagnostic challenge. Advances in treatment also demand tissue is analysed for multiple molecular anomalies therefore pathologists must be judicious in their use of ancillary tests such as immunohistochemistry. Whilst the majority of tumours encountered are non-small cell lung carcinomas, the lungs and thorax are a common metastatic site and can display a wide variety of different tumour types. Some tumours can closely mimic the appearances of non-small cell carcinomas and failure to recognise these can result in misdiagnosis and incorrect treatment and management for the patient. In this article we specifically focus on a variety of different tumours that can masquerade as non-small cell carcinomas. This includes both benign and malignant primary lung tumours, sarcomas, melanomas and germ cell tumours. We describe how to approach and recognise these entities, with specific focus on the histological and immunohistochemical appearances, and identify potential pitfalls to avoid in routine practice. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

The combination of pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor, shows synergistic activity in preclinical and clinical studies in solid tumours. We assessed the clinical activity of this combination therapy in patients with pleural mesothelioma who progressed after platinum-pemetrexed chemotherapy. In this single-arm, single-centre, phase 2 study, done at the Netherlands Cancer Institute in Amsterdam, The Netherlands, eligible patients (aged ≥18 years) with pleural mesothelioma with an Eastern Cooperative Oncology Group performance status of 0–1, progression after chemotherapy (no previous immunotherapy), and measurable disease according to the modified Response Evaluation Criteria In Solid Tumours (mRECIST) for mesothelioma version 1.1. Patients received 200 mg intravenous pembrolizumab once every 3 weeks plus 20 mg oral lenvatinib once per day for up to 2 years or until disease progression, development of unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate identified by a local investigator according to mRECIST version 1.1. This trial is registered with ClinicalTrials.gov , NCT04287829 , and is recruiting for the second cohort. Between March 5, 2021, and Jan 31, 2022, 42 patients were screened, of whom 38 were included in the primary endpoint and safety analyses (median age 71 years [IQR 65–75], 33 [87%] male and five [13%] female). At data cutoff (Jan 31, 2023), with a median follow-up of 17·7 months (IQR 13·8–19·4), 22 (58%; 95% CI 41–74) of 38 patients had an objective response. The independent review showed an objective response in 17 (45%; 95% CI 29–62) of 38 patients. Serious treatment-related adverse events occurred in ten (26%) patients, including one treatment-related death due to myocardial infarction. The most common treatment-related grade 3 or worse adverse events were hypertension (eight patients [21%]) and anorexia and lymphopenia (both four patients [11%]). In 29 (76%) of 38 patients, at least one dose reduction or discontinuation of lenvatinib was required. Pembrolizumab plus lenvatinib showed promising anti-tumour activity in patients with pleural mesothelioma with considerable toxicity, similar to that in previous studies. Available evidence from the literature suggests a high starting dose of lenvatinib for optimal anti-tumour activity. This, however, demands a high standard of supportive care. The combination therapy of pembrolizumab and lenvatinib warrants further investigation in pleural mesothelioma. Merck Sharp & Dohme. [ABSTRACT FROM AUTHOR]

Malignant mesotheliomas with localized growth are extremely rare in dogs. A 9-year-old male dog presented with a localized tumour that originated from the parietal pleura and had polypoid growth in the thoracic cavity. Histological examination revealed that the tumour consisted of tubular formations with scattered cysts and minimal papillary growth pattern. Neoplastic cells were immunopositive for mesothelial markers (calretinin and Wilms' tumour gene 1) and negative for carcinoma markers (thyroid transcription factor 1 and tumour protein 63). The animal was alive with no recurrence or metastasis/dissemination 11 months after surgery. To the best of our knowledge, this is the first report of a localized mesothelioma in a dog without metastasis/dissemination and highlights the value of mesothelial markers for an accurate diagnosis. [ABSTRACT FROM AUTHOR]

Limited second-line therapeutic options are available in Malignant Pleural Mesothelioma (MPM). In this patients Stereotactic Ablative Body Radiotherapy (SABR) could postpone the begin of a second-line systemic therapy in those with radiological findings of oligorecurrent disease. Primary aim of our study was to determine the time to second-line systemic therapy (TTST) in this setting. In this population we also evaluated Progression-Free Survival (PFS) and Overall Survival (OS). All patients with MPM enrolled in this analysis were previously treated with platinum-based chemotherapy, surgery (thoracoscopic biopsy, pleural decortication or pleurectomy plus decortication), Radical Hemithoracic Radiotherapy (RHR). An additional inclusion criteria was a minimum follow-up of 6 months. During the first radiotherapy course, all the patients received a total dose of 50 Gy in 25 fractions with a concomitant boost of 60 Gy to PET/TC positive macroscopic residual disease. Patients showing an oligorecurrent ipsilateral pleural disease (defined as radiological evidence of lesion numbers ≤ 3) underwent SABR re-irradiation following a fractionation scheme of 25-30 Gy in 3-5 daily fractions. TTST was defined as the time between the first day of SABR retreatment and the first day of second-line systemic treatment. PFS was defined as the time between SABR re-irradiation and the first radiological finding of disease progression, while OS was defined as the time between SABR retreatment and the patient death. All considered outcomes were calculated with Kaplan-Meier method. Toxicities of RHR and SABR re-irradiation were assessed with Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Twenty-two patients were treated between January 2011 and December 2022, with a median follow-up of 11.4 months (6-36 months). At the time of analysis, only 5 patients were alive, including 2 patients with no evidence of disease. After SABR re-irradiation, only 9 patients developed a plurimetastatic disease (3 patients with extensive local progression and 6 patients with distant progression) and started a second-line systemic treatment. Median TTST was 10.2 months [Q1-Q3: 4.8-17.1]. PFS rates at 6,12, 36 months were 71.8% [47.6%-86.2%], 33.5% [15.0%-53.3%] and 14% [3.6%-32.2%], respectively. OS rates at 6,12, 36 months were 95.2% [70.7%-99.3%], 56.4% [32.8%-74.5%], 27.4% [9.5%-48%], respectively. Only one patient developed acute G2 gastrointestinal toxicity while no other acute or late toxicities were reported. Results of a very homogeneous population were reported in this study. SABR re-irradiation in patients with oligorecurrent MPM appears to be safe and useful to postpone second-line systemic treatment. Further prospective studies and randomized trials are needed to support our findings. [ABSTRACT FROM AUTHOR]

Early guidelines for minimally important differences (MIDs) for the EORTC QLQ-C30 proposed ≥10 points change as clinically meaningful for all scales. Increasing evidence that MIDs can vary by scale, direction of change, cancer type and estimation method has raised doubt about a single global standard. This paper identifies MID patterns for interpreting group-level change in EORTC QLQ-C30 scores across nine cancer types. Data were obtained from 21 published EORTC Phase III trials that enroled 13,015 patients across nine cancer types (brain, colorectal, advanced breast, head/neck, lung, mesothelioma, melanoma, ovarian, and prostate). Anchor-based MIDs for within-group change and between-group differences in change over time were obtained via mean change method and linear regression, respectively. Separate MIDs were estimated for improvements and deteriorations. Distribution-based estimates were derived and compared with anchor-based MIDs. Anchor-based MIDs mostly ranged from 5 to 10 points. Differences in MIDs for improvement vs deterioration, for both within-group and between-group, were mostly within a 2-points range. Larger differences between within-group and between-group MIDs were observed for several scales in ovarian, lung and head/neck cancer. Most anchor-based MIDs ranged between 0.3 SD and 0.5 SD distribution-based estimates. Our results reinforce recent claims that no single MID can be applied to all EORTC QLQ-C30 scales and disease settings. MIDs varied by scale, improvement/deterioration, within/between comparisons and by cancer type. Researchers applying commonly used rules of thumb must be aware of the risk of dismissing changes that are clinically meaningful or underpowering analyses when smaller MIDs apply. • MID patterns for interpreting group-level change are examined by QLQ-C30 scales. • Data were obtained from 21 published EORTC clinical trials across 9 cancer types. • MIDs varied by scale, improve/deteriorate, within/between groups and cancer type. • Our results reinforce claims that no single MID applies to all QLQ-C30 scales. • We present diversified MIDs to inform more accurate sample size calculations. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is an aggressive, almost universally fatal cancer with limited therapeutic options. Despite efforts, a real breakthrough in treatment and outcomes has been elusive. Pleural effusion with significant breathlessness and pain is the most typical presentation of individuals with MPM. Although thoracentesis provides relief of breathlessness, most such pleural effusions recur rapidly, and a definitive procedure is often required to prevent a recurrence. Unfortunately, the optimal treatment modality for individuals with recurrent MPM-related effusion is unclear, and considerable variation exists in practice. In addition, non-expandable lung is common in pleural effusions due to MPM and makes effective palliation of symptoms more difficult. This review delves into the latest advances in the available management options (both surgical and non-surgical) for dealing with pleural effusion and non-expandable lung related to MPM. We discuss factors that determine the choice of definitive procedures that need to be tailored to the individual patient. [ABSTRACT FROM AUTHOR]

Mesothelioma is a nearly uniformly fatal tumor. Multimodality therapy including cytoreductive surgery and chemotherapy is associated with long-term survival in some patients. Cytoreductive surgery for thoracic disease includes a lung-sparing operation called an "extended pleurectomy/decortication" or a lung-sacrificing surgery called an "extrapleural pneumonectomy." The benefit of cytoreductive surgery for bicavitary disease (chest and abdomen) is poorly understood. Our objective was to evaluate the long-term survivals for patients undergoing cytoreductive surgery for bicavitary disease and to determine whether any prognostic factors were associated with outcome. We reviewed our Institutional Review Board–approved, institutional, International Association for the Study of Lung Cancer Mesothelioma Staging Project database. Inclusion criteria were all patients who underwent cytoreductive surgery for bicavitary disease. Overall survival was calculated by Kaplan–Meier methodology. All International Association for the Study of Lung Cancer database elements were evaluated by univariable analysis. From February 2014 to August 2021, 440 patients with mesothelioma were evaluated. Fourteen patients (3%) underwent cytoreductive surgery of both chest and abdomen as a planned 2-stage operation. Most patients (13/14; 93%) underwent chest surgery before abdomen surgery. For the entire cohort, the median overall survival was 33.6 months with a 5-year survival of 20%. Extended pleurectomy/decortication was associated with a better outcome compared with extrapleural pneumonectomy, with median overall survivals of 58.2 versus 13.5 months, respectively. For a highly selected group of patients with bicavitary mesothelioma, long-term survival can be achieved with an aggressive, staged surgical approach. The patients who undergo extended pleurectomy/decortication with preservation of the lung appear to have more favorable outcomes compared with patients undergoing extrapleural pneumonectomy. [ABSTRACT FROM AUTHOR]

• TROP2 expression is detected in a panel of fifteen novel mesothelioma cell models. • A large portion of mesothelioma cells show sensitivity to SN38 treatment. • High Aurora kinase-A expression predicts sensitivity to the topoisomerase I inhibitor SN38. • Sacituzimab govitecan (anti-TROP2 antibody SN38 conjugate) can induce apoptosis in TROP2 expressing MPM cells. • Biomarker-selected exploration of sacituzimab govitecan in mesothelioma is warranted. Malignant pleural mesothelioma (MPM) is an aggressive cancer which at large is not amenable to curative surgery. Despite the recent approval of immune checkpoint inhibitor therapy, the response rates and survival following systemic therapy is still limited. Sacituzumab govitecan is an antibody-drug conjugate targeting the topoisomerase I inhibitor SN38 to trophoblast cell-surface antigen 2 (TROP-2)-positive cells. Here we have explored the therapeutic potential of sacituzumab govitecan in MPM models. TROP2 expression was analyzed in a panel of two well established and 15 pleural effusion derived novel lines by RT-QPCR and immunoblotting, TROP2 membrane-localization was studied by flow cytometry and immunohistochemistry. Cultured mesothelial cells and pneumothorax pleura served as controls. The sensitivity of MPM cell lines to irinotecan and SN38 was studied using cell viability, cell cycle, apoptosis and DNA damage assays. Drug sensitivity of cell lines was correlated with RNA expression of DNA repair genes. Drug sensitivity was defined as an IC50 below 5 nM in the cell viability assay. TROP2 expression was detected at RNA and protein level in 6 of the 17 MPM cell lines, but not in in cultured mesothelial control cells or in the mesothelial layer of the pleura. TROP2 was detectable on the cell membrane in 5 MPM lines and was present in the nucleus in 6 cell models. Ten of 17 MPM cell lines showed sensitivity to SN38 treatment, among those 4 expressed TROP2. High AURKA RNA expression and high proliferation rate correlated with sensitivity to SN38-induced cell death, DNA damage response, cell cycle arrest and cell death. Sacituzumab govitecan treatment effectively induced cell cycle arrest and cell death in TROP2-positive MPM cells. TROP2 expression and sensitivity to SN38 in MPM cell lines support biomarker-selected clinical exploration of sacituzumab govitecan in patients with MPM. [ABSTRACT FROM AUTHOR]

• Standard of care for pleural mesothelioma has not changed for 20 years. • Repurposing of already approved drugs may result in more effective therapies. • Functional drug sensitivity testing with pleural effusion-derived cells is feasible. • mTOR and Chk1 pathways may be viable targets when treating pleural mesothelioma. Pleural mesothelioma (PM) is an aggressive malignancy with limited treatment options. The first-line therapy has remained unchanged for two decades and consists of pemetrexed in combination with cisplatin. Immune-checkpoint inhibitors (nivolumab plus ipilimumab) have high response rates, resulting in recent updates in treatment recommendations by the U.S. Food and Drug Administration. However, the overall benefits of combination treatment are modest, suggesting that other targeted therapy options should be investigated. We employed high-throughput drug sensitivity and resistance testing on five established PM cell lines using 527 cancer drugs in a 2D setting. Drugs of the greatest potential (n = 19) were selected for further testing in primary cell models derived from pleural effusions of seven PM patients. All established and primary patient-derived PM cell models were sensitive to the mTOR inhibitor AZD8055. Furthermore, another mTOR inhibitor (temsirolimus) showed efficacy in most of the primary patient-derived cells, although a less robust effect was observed when compared with the established cell lines. Most of the established cell lines and all patient-derived primary cells exhibited sensitivity to the PI3K/mTOR/DNA-PK inhibitor LY3023414. The Chk1 inhibitor prexasertib showed activity in 4/5 (80%) of the established cell lines and in 2/7 (29%) of the patient-derived primary cell lines. The BET family inhibitor JQ1 showed activity in four patient-derived cell models and in one established cell line. mTOR and Chk1 pathways had promising results with established mesothelioma cell lines in an ex vivo setting. In patient-derived primary cells, drugs targeting mTOR pathway in particular showed efficacy. These findings may inform novel treatment strategies for PM. [ABSTRACT FROM AUTHOR]

Mesothelioma is a rare but highly aggressive malignancy with poor prognosis that frequently present with recurrent effusions. Establishing the diagnosis by cytology can lead to early diagnosis and treatment and consequently improve prognosis. This review examines the cytological diagnosis of mesothelioma in the context of its historical and morphologic evolution and provides an update of the current reporting systems. Clues to identify the mesothelial and malignant nature of the sample are detailed as well as the supporting ancillary tests. Cytologically, the samples are overwhelmingly cellular and malignancy is recognized by both architectural and cytological atypia. Numerous variably sized clusters and enlarged cells are easily identified, some with papillary architecture and collagen cores. Recognizing the mesothelial nature of the cells and supportive immunostains are essential to rule out the differential diagnosis of metastatic carcinomas and reactive mesothelium. Current ancillary tests such as homozygous deletion of CDKN2A, loss of BRCA1-associated protein, and methylthioadenosine phosphorylase expression can provide further support of malignancy. At this time with the aid of current ancillary tests and in the hands of cytopathologists with adequate experience with the interpretation of effusions, the diagnosis of mesothelioma can be established with accuracy in most cases. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

The main modality of management of paratesticular mesothelioma remains orchiectomy while the use of adjuvant chemotherapy has not yet been explored. We aim to analyse the outcome of the multimodal management protocol in testicular mesothelioma We conducted a retrospective analysis of patients registered and treated for testicular mesothelioma between 2009 and 2019 in an oncology tertiary care hospital. Patients presenting with nodal, metastatic disease were treated with adjuvant, palliative chemotherapy respectively and their response to treatment was periodically monitored. Eight patients (3 early, 1 nodal, 4 metastatic) with median age of 58 years was included in the study. Patients who had limited (early, nodal) disease (n = 4) had overall survival ranging from 20 to 140 months while metastatic disease (n = 4) had poor outcomes with overall survival ranging from 2 to 13 months. Surgery remains to be an important modality of therapy that improves the local control and overall outcomes and the quality of life even in patients with metastatic disease at the time of diagnosis. Adjuvant chemotherapy might play a role in effective management of locoregional disease. The performance status, the extent of disease at the time of presentation are the important prognostic factors in deciding the outcome of the disease management. [ABSTRACT FROM AUTHOR]

The standard evaluation of older lung cancer or mesothelioma patients for systemic anti-cancer treatment, based on performance status, is inaccurate. We used the G8 questionnaire to assess a patient's fitness for chemotherapy and explored the correlations between G8 scores, treatment decisions and clinical outcomes. In total, 201 older patients (≥70 years) with advanced lung cancer or mesothelioma were prospectively assessed by standard clinical methods and a G8 questionnaire. Treatment decisions before and after reviewing the G8 score were documented. Patients were divided into low (<11), intermediate (11–14) and high (>14) G8 score groups. Patients' characteristics, treatment plans and clinical outcomes among each G8 score group were compared. Similar analyses were compared between good (<2) and poor (≥2) performance status. 10.1% of patients' treatment plans changed after oncologists reviewed G8 scores. The G8 score correlated inversely with performance status. More patients with low G8 scores (22.5%) were offered the best supportive care compared with 4.5% in intermediate and 1.9% in high G8 score groups. More patients (30.1%) with low G8 scores had treatment changed from chemotherapy to best supportive care on the planned day of their treatment, compared with intermediate (7.5%) and high (6.1%) G8 score groups. High G8 score patients received higher chemotherapy intensity and survived longer than patients with intermediate or low G8 scores. The G8 score with two cut-off values can predict functional status, chemotherapy tolerability and prognosis in older patients with lung cancer or mesothelioma, thus supporting oncologists on treatment decisions for this population. • The G8 scores correlate inversely with performance status. • Low G8 scores can predict a rapid functional decline of older patients with lung cancer or mesothelioma. • The G8 score with two cut-off values can predict chemotherapy tolerability and prognosis. • Our findings reinforce the clinical utility of the G8 scores to support oncologists on treatment decisions and chemotherapy intensity. [ABSTRACT FROM AUTHOR]

• NF2 hemizygous loss (HL, 90%: monosomy) seen in 49–54% of pleural mesothelioma (PM). • No CDKN2A homozygous deletion (HD) or NF2 HL in benign mesothelial lesion (BML). • [ NF2 HL + BAP1 loss + CDKN2A HD] yields > 95 % sensitivity in distinguishing PM from BML. • CDKN2A HD significantly affects overall survival, while BAP1 loss and NF2 HL do not. BAP1 , CDKN2A , and NF2 are the most frequently altered genes in pleural mesotheliomas (PM). Discriminating PM from benign mesothelial proliferation (BMP) is sometimes challenging; it is well established that BAP1 loss, determined by immunohistochemistry (IHC), and CDKN2A homozygous deletion (HD), determined by fluorescence in situ hybridization (FISH), are useful. However, data regarding the diagnostic utility of NF2 FISH in PM is limited. Thus, we performed a multi-institutional study examining the utility of NF2 alterations determined by FISH for diagnosing PM in combination with BAP1 loss and CDKN2A HD. Multi-institutional PM cases, including 106 surgical and 107 cell block samples as well as 37 tissue cases of benign mesothelial proliferation (BMP) and 31 cell block cases with reactive mesothelial cells (RMC), were collected and analyzed using IHC for BAP1 and FISH for CDKN2A and NF2. In PM, NF2 FISH revealed hemizygous loss (HL) in 54.7% of tissue cases (TC) and 49.5% of cell block cases (CBC), with about 90% of HL being monosomy. CDKN2A HD or BAP1 loss were detected in 75.5%/65.4% TC or 63.6%/60% CBC, respectively. BMP or RMC showed no BAP1 loss, CDKN2A HD, or NF2 HL. For discriminating PM from BMP, a combination of BAP1 loss, CDKN2A HD, and NF2 HL yielded enhanced sensitivity of 98.1% TC/94.4% CBC. BAP1 loss, CDKN2A HD, or NF2 HL were observed in 69%, 70%, or 58% of epithelioid PM, but in 9%, 91%, or 27% of sarcomatoid PM, respectively. Histotype, histological gradings, and CDKN2A deletion status showed significant differences in overall survival, while BAP1 loss and NF2 HL did not. NF2 HL, consisting predominantly of monosomy, can be detected by FISH in both TC and CBC of PM, and is effective for distinguishing PM from BMP, especially when combined with BAP1 loss and CDKN2A HD. [ABSTRACT FROM AUTHOR]

• The combination of anetumab ravtansine and pembrolizumab were considered safe. • There were no significant differences in response rates or progression free survival between the combination of anetumab ravtansine and pembrolizumab and pembrolizumab alone, possibly related to a smaller than planned sample size. • High levels of soluble mesothelin were associated with poor survival with anetumab ravtansine. • Soluble mesothelin may help select against the use of anti-mesothelin antibodies that are neutralized by mesothelin, but not with pembrolizumab alone. The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma. A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network. Patients with pleural mesothelioma that expressed mesothelin and had previously received platinum-based therapy were eligible. In phase 1 (n = 12) only one dose limiting toxicity was observed and the rules for dose reduction were not met. In phase 2, there was no difference in the confirmed response rates between the combination group (n = 18, 2 partial responses [PR], 11 %) and the pembrolizumab group (n = 17, 1 PR, 6 %; z = -0.5523, p = 0.29116). The median PFS was 12.2 months (95 % CI 5.1–not evaluable [NE]) for the combination, and 3.9 months for pembrolizumab (95 % CI 2.1-NE)(HR=0.55, p = 0.20). Patients with high baseline levels of soluble mesothelin who received anetumab ravtansine had a median PFS of 5 months. The numeric difference in PFS between treatment groups was not statistically significant, likely related to a smaller than planned sample size. High levels of soluble mesothelin should potentially be considered to select against the use of mesothelin-targeting therapies in development that are neutralized by soluble mesothelin. [ABSTRACT FROM AUTHOR]

• One of the largest cohort studies of asbestos-exposed workers. • Retrospective exposure assessment. • New considerations on latency until death. The time between initial asbestos exposure and asbestos-related disease can span several decades. The Asbestos Surveillance Program aims to detect early asbestos-related diseases in a cohort of 8,565 power industry workers formerly exposed to asbestos. How does asbestos exposure patterns affect cancer mortality and the duration of latency until death? A mortality follow-up was conducted with available vital status for 8,476 participants (99 %) and available death certificates for 89.9 % of deceased participants. Standardised mortality ratios (SMR) were calculated for asbestos-related cancers. The SMR of mesothelioma and lung cancer were stratified by exposure duration, cumulative asbestos exposure and smoking. The effect of age at first exposure, cumulative asbestos exposure and smoking on the duration of latency until death was examined using multiple linear regression analysis. The mortality risk of mesothelioma (n = 104) increased with cumulative asbestos exposure but not with exposure duration; the highest mortality (SMR: 23.20; 95 % CI: 17.62–29.99) was observed in participants who performed activities with short extremely high exposures (steam turbine revisions). Lung cancer mortality (n = 215) was not increased (SMR: 1.03; 95 % CI: 0.89–1.17). Median latency until death was 46 (15–63) years for mesothelioma and 44 (15–70) years for lung cancer and deaths occurred between age 64 and 82 years. Latency until death was not influenced by age at first exposure, cumulative exposure, or smoking. Cumulative dose seems to be more appropriate than exposure duration for estimating the risk of mesothelioma death. Additionally, exposure with high cumulative doses in short time should be considered. Since only lung cancer mortality, not incidence, was recorded in this study, lung cancer risk associated with asbestos exposure could not be assessed and the lung cancer mortality was lower than expected probably due to screening effects and improved treatments. The critical time window of death from asbestos-related cancer is between the seventh and ninth decade of life. Future studies should further explore the concept of latency, especially since large ranges are reported throughout the literature. [ABSTRACT FROM AUTHOR]

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1 – 7) were isolated, along with four non-stilbenes (8 – 11), of which compounds 4 and 9 – 11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4′-tetrahydroxystilbene 2- O - β - d -quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1 , 4 , 6 , and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM. [Display omitted] • A new (1) and six reported (2 – 7) stilbenes were obtained from Polygonum multiflorum. • Three non-stilbenes (9 – 11) were isolated from P. multiflorum for the first time. • Stilbenes 1 , 4 , and 6 showed significant inhibitory effects on H2452 cells. • Emodin (8), an anthraquinone, significantly inhibited H2452 cells. [ABSTRACT FROM AUTHOR]

• Nivolumab plus ipilimumab is an effective treatment for malignant pleural mesothelioma. • Biopsies before nivolumab plus ipilimumab treatment show a higher cell density of CD4+, CD8+, FoxP3+ and PD-1+ cells in responding patients. • Biopsies during treatment with checkpoint inhibitors do not show a significant change when compared to baseline. • Larger trials are needed with a more detailed analysis of mesothelioma tumor microenvironment. Malignant pleural mesothelioma (MPM) is a malignant disease of the pleura which recently can be treated with immune checkpoint inhibitors (ICI). To optimize this treatment, a better understanding of the tumor micro environment is needed. We investigated subgroups of immune cells in subsequent tumor biopsies of patients treated with ICI. Biopsies from MPM patients included in two clinical ICI trials (nivolumab alone and an ipilimumab/nivolumab combination) were examined. At baseline and after 6 weeks of treatment, pleural biopsies were taken to examine the tumor microenvironment (CD20+, CD4+, CD8+, FoxP3+ and PD-1+). Cell density was defined as the number of marker positive cells per mm2. Radiological responses were evaluated as partial response, stable disease or progressive disease according to modified RECIST criteria. Thirty-four and 36 patients were included in the nivolumab and ipiliumumab/nivolumab trial respectively. In the nivolumab trial, no significant differences in cell densities were seen in baseline biopsies of patients with partial response versus progressive disease. In contrast, in the ipilimumab/nivolumab trial, a higher cell density of CD4+, CD8+, FoxP3+ and PD-1+ cells at baseline was significantly correlated with partial responses. On-treatment biopsies of both trials did not show significant changes when compared to baseline biopsies. Biopsies from patients responding to nivolumab plus ipilimumab treatment show a significant higher cell density of CD4+, CD8+, FoxP3+ and PD-1+ cells, without a change after 6 weeks of treatment. This observation is a first step in exploring the tumor microenvironment as predictor of response in ICI treatment in MPM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Serous effusion is often the first sign of mesothelioma. Diagnosis based on cytologic material from the effusions remains controversial and complementary biopsy is usually required. However, obtaining representative tissue sample may be challenging, while obtaining cytologic material is a minimally invasive procedure, providing potential for an earlier diagnosis. Loss of BRCA1-associated protein (BAP1), combined with loss of methylthionadenosine phosphorylase (MTAP) detected by immunohistochemistry, have shown to be reliable markers in the diagnosis of mesothelioma on histologic sections. Here we evaluate the value of these biomarkers in cytologic specimens. The BAP1 and MTAP expression in specimens of 162 mesothelioma patients (156 pleural, 6 peritoneal)—71 cytologic, 91 histologic (44 epithelioid, 31 biphasic, 16 sarcomatoid)—and 20 patients with reactive mesothelial proliferations were investigated. The loss of BAP1 and/or MTAP was highly sensitive and specific in differentiating mesothelioma from reactive mesothelial proliferations, with no significant difference between pleural effusions and biopsies, specificity of 100% in both and a sensitivity of 78.9% and 80.2%, respectively (P = 0.3). There was a 100% concordance of the expression of BAP1 and MTAP in cytologic and corresponding histopathologic samples. Loss of BAP1 and/or MTAP in histologic sections discriminated sarcomatoid, biphasic, and epithelioid mesothelioma from reactive mesothelial proliferations with a sensitivity of 81.2%, 83.9%, and 77.3% respectively. Loss of expression of BAP1 and/or MTAP differentiated mesothelioma from reactive mesothelial proliferations with excellent specificity and high sensitivity in cytologic samples, comparable to histopathologic sections. • Loss of BAP1 and/or MTAP by immunohistochemistry can distinguish malignant mesothelioma cells from reactive mesothelial proliferations in cytology samples comparably to histology sections with excellent specificity and good sensitivity. • However, a negative cytology should not be used to exclude malignant mesothelioma due to a lower sensitivity of both markers and the fact that sarcomatoid subtype rarely sheds cells into pleural or peritoneal effusions and therefore may not be detected. [ABSTRACT FROM AUTHOR]

Lurbinectedin is a promising new drug being investigated in pre-treated patients with small cell lung cancer (SCLC) or malignant pleural mesothelioma (MPM). Its clinical activity in the real-world setting has not been investigated yet. Clinical data of patients with SCLC and MPM who were treated with lurbinectedin were prospectively collected. Comprehensive immune cell profiling by flow cytometry was performed on screening and treating peripheral blood samples. A total of 95 patients (43 SCLC and 52 MPM) were treated, mostly as ≥3-line of therapy. In the SCLC cohort, a median progression-free survival (mPFS) was 1.5 months (95% CI: 1.4–3.0), and median overall survival was 7.0 months (95% CI: 4.7–not reached). Objective radiological response and disease control rate after 12 weeks were 16% and 28%, respectively. In the MPM cohort, median progression-free survival was 2.8 months (95% CI: 1.4–4.2), and median overall survival was 7.2 months (95% CI: 5.9–not reached). Disease control rate after 12 weeks was 29%, whereas no partial responses were registered. No new safety signals were observed. Lurbinectedin treatment was significantly associated with the depletion of circulating classical monocytes, which correlated with a better PFS in patients with SCLC. Lurbinectedin increased the proliferation of CD4+ and CD8+ T cells (SCLC) and natural killer and natural killer T cells (SCLC and MPM) and altered co-stimulatory and co-inhibitory receptor expression on circulating lymphocytes. Lurbinectedin has a manageable safety profile and shows clinical activity in pre-treated patients with SCLC and MPM. Its immune-modulatory functions make lurbinectedin a potential platform for immunotherapy combinations. • Lurbinectedin was effective in heavily pre-treated patients with small cell lung cancer with objective response rate 16%. • In patients with pre-treated malignant mesothelioma (MM), the disease control rate of lurbinectedin after 12 weeks was 29%. • No new safety signals of lurbinectedin were observed in the real-world setting. • Lurbinectedin displays specific immune-modulatory effects. • Lurbinectedin seems to be a potential platform for immunotherapy combinations. [ABSTRACT FROM AUTHOR]

• Machine learning algorithms can be used to distinguish mesothelioma and lung cancer. • Pleural carcinosis and pleomorphic lung cancer retain lung-specific methylation profiles. • Differential methylation analysis highlights novel candidate genes in mesothelioma. • Deconvolution of bulk methylation data can inform about the tumor composition. Our goal was to evaluate the diagnostic value of DNA methylation analysis in combination with machine learning to differentiate pleural mesothelioma (PM) from important histopathological mimics. DNA methylation data of PM, lung adenocarcinomas, lung squamous cell carcinomas and chronic pleuritis was used to train a random forest as well as a support vector machine. These classifiers were validated using an independent validation cohort including pleural carcinosis and pleomorphic variants of lung adeno- and squamous cell carcinomas. Furthermore, we performed differential methylation analysis and used a deconvolution method to estimate the composition of the tumor microenvironment. T-distributed stochastic neighbor embedding clearly separated PM from lung adenocarcinomas and squamous cell carcinomas, but there was a considerable overlap between chronic pleuritis specimens and PM with low tumor cell content. In a nested cross validation on the training cohort, both machine learning algorithms achieved the same accuracies (94.8%). On the validation cohort, we observed high accuracies for the support vector machine (97.8%) while the random forest performed considerably worse (89.5%), especially in distinguishing PM from chronic pleuritis. Differential methylation analysis revealed promoter hypermethylation in PM specimens, including the tumor suppressor genes BCL11B , EBF1 , FOXA1, and WNK2. Deconvolution of the stromal and immune cell composition revealed higher rates of regulatory T-cells and endothelial cells in tumor specimens and a heterogenous inflammation including macrophages, B-cells and natural killer cells in chronic pleuritis. DNA methylation in combination with machine learning classifiers is a promising tool to reliably differentiate PM from chronic pleuritis and lung cancer, including pleomorphic carcinomas. Furthermore, our study highlights new candidate genes for PM carcinogenesis and shows that deconvolution of DNA methylation data can provide reasonable insights into the composition of the tumor microenvironment. [ABSTRACT FROM AUTHOR]

• Malignant mesothelioma prognostic baseline clinical and laboratory parameters. • Randomized trial on second line pembrolizumab or single agent chemotherapy. • Stratified multivariate analysis. • High systemic immune-inflammatory index and low hemoglobin associated with worse PFS. • Definition of a mesothelioma risk score based on these two factors. Clinical and laboratory parameters associated with response for patients with advanced pre-treated malignant pleural mesothelioma (MPM) are lacking. We aimed to identify prognostic and predictive markers among patients with relapsed MPM who were randomised into the ETOP 9–15 PROMISE-meso phase III trial, evaluating pembrolizumab and chemotherapy. Baseline clinical and laboratory parameters were investigated for prognostic or predictive value on progression-free survival (PFS) and overall survival (OS) in a retrospective analysis, based on the full cohort of 144 MPM patients. These consisted of immune-inflammatory indexes (neutrophil–lymphocyte ratio [NLR], systemic immune-inflammatory index [SII], lactate dehydrogenase [LDH]) along with other already known prognostic baseline characteristics and laboratory values. Cut-offs were chosen independently of outcome. Based on Cox multivariable analysis for PFS in the whole cohort, a risk factor model was built to illustrate the prognostic stratification of patients by the combination of the derived independent prognostic factors, taking into account the EORTC score, a validated prognostic score in MPM. All models were stratified by histology and adjusted by treatment. In the stratified multivariable analysis in the whole cohort, high SII (hazard ratio (HR) 2.06; 95%CI 1.39–3.05) and low haemoglobin (HR 1.62; 95%CI 1.06–2.50) were associated with worse PFS. Based on these two prognostic factors, a mesothelioma risk score (MRS) was constructed with three PFS risk prognosis categories: favourable, intermediate and poor with 0, 1 and 2 risk factors, respectively (corresponding percent of cohort: 24%, 34% and 42% and median PFS: 5.8, 4.2 and 2.1 months). The derived MRS stratified the prognosis for PFS and OS, overall and within each of the EORTC groups. No significant predictors of treatment benefit were identified. The proposed MRS is prognostic of patient outcome and it fine-tunes the prognosis of patients with pre-treated MPM alone or when used with the already established EORTC score. [ABSTRACT FROM AUTHOR]

Objective: Practice guidelines emphasize the importance of investigating psychosocial distress in mesothelioma patients and family caregivers. We aimed to synthesize research on the psychosocial support needs of mesothelioma patients and their family caregivers.Methods: We conducted a systematic review with a narrative synthesis and quality assessment. The review process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Results: MEDLINE, EMBASE, Scopus, PsychArticles, and PsycINFO were searched until December 2020 and 37 studies in English met inclusion criteria. Most (n = 24) included mesothelioma patients as a very small proportion of their cancer samples. A narrative synthesis was conducted on the 13 studies including only mesothelioma patients (n = 297) and/or caregivers (n = 82). Patients and caregivers want improvements in the diagnosis delivery and access to palliative care. Patients want emotional support, patient-centered treatment, improved information about illness progression and death, and to meet others with mesothelioma. Caregivers want one-on-one practical and emotional support. Study quality varied.Conclusions: Few studies focus on the psychosocial support needs relevant to mesothelioma. Mesothelioma patients and family caregivers highlight targeted psychosocial care as an unmet need.Practice Implications: Efforts are required to design and test psychosocial interventions for this vulnerable and overlooked group.Protocol Registration: PROSPERO (registration number CRD42020167852). [ABSTRACT FROM AUTHOR]

Patients who did not receive CRS-HIPEC had the lowest average life expectancy of 2.11 years overall survival. Keywords: Cytoreductive surgery; HIPEC; Malignant peritoneal mesothelioma; Time to treatment; Markov EN Cytoreductive surgery HIPEC Malignant peritoneal mesothelioma Time to treatment Markov 995 997 3 04/28/23 20230501 NES 230501 Presented as a Quick Shot presentation at the 63rd Annual Meeting of the Society for Surgery of the Alimentary Tract, May 21-24, 2022, San Diego, CA. [Extracted from the article]

• Study reveals prognostic significance of 24 ferroptosis regulators in mesothelioma, identifying 9 genes (CARS1, CDKN1A, TFRC, FANCD2, FDFT1, HSPB1, SLC1A5, SLC7A11, DPP4) closely linked to outcomes. • Novel ferroptosis prognostic model, using nine genes, predicts mesothelioma survival accurately. Genes correlate with immune cell infiltration, tumor mutation burden, microsatellite instability, and PD-L1 expression. • High FANCD2 signals poor prognosis in mesothelioma. Knocking it down suppresses cell activities, heightens ferroptosis susceptibility, and correlates with immune checkpoint gene expression across cancers. Mesothelioma, an uncommon yet highly aggressive malignant neoplasm, presents challenges in the effectiveness of current therapeutic approaches. Ferroptosis, a non-apoptotic mechanism of cellular demise, exhibits a substantial association with the progression of diverse cancer forms. It is important to acknowledge that there exists a significant association between ferroptosis and the advancement of various forms of cancer. Nevertheless, the precise role of ferroptosis regulatory factors within the context of mesothelioma remains enigmatic. In our investigation, we initially scrutinized the prognostic significance of 24 ferroptosis regulatory factors in the realm of mesothelioma. Our observations unveiled that heightened expression levels of CARS1, CDKN1A, TFRC, FANCD2, FDFT1, HSPB1, SLC1A5, SLC7A11, coupled with reduced DPP4 expression, were indicative of an unfavorable prognosis. Built upon the nine previously discussed prognostic genes, the ferroptosis prognostic model offers a reliable means to forecast mesothelioma patients' survival with a substantial degree of precision. Furthermore, a notable correlation emerged between these prognostic ferroptosis regulators and parameters such as immune cell infiltration, tumor mutation burden, microsatellite instability, and PD-L1 expression in the context of mesothelioma. Within this cadre of nine ferroptosis regulatory factors with prognostic relevance, FANCD2 exhibited the most pronounced prognostic influence, as elucidated by our analyses. Subsequently, we executed a validation process employing clinical specimens sourced from our institution, thus confirming that heightened FANCD2 expression is a discernible harbinger of an adverse prognosis in the context of mesothelioma. In vitro experiments revealed that knocking down FANCD2 markedly suppressed the proliferation, migration, and ability of mesothelioma cells to attract immune cells. Furthermore, our findings also showed that reducing FANCD2 levels heightened the vulnerability of mesothelioma cells to inducers of ferroptosis. Furthermore, an extensive pan-cancer analysis uncovered a robust association between FANCD2 and the gene expression linked to immune checkpoints, thereby signifying an adverse prognosis across a broad spectrum of cancer types. Additional research is warranted to validate these findings. [ABSTRACT FROM AUTHOR]

To assess the potential of apparent diffusion coefficient (ADC) values derived from diffusion weighted (DW) MRI preoperatively to predict the predominant histologic component among biphasic pleural mesothelioma (PM) tumors. ADC maps were generated from DW MRI scans. Histology and predominant component of biphasic PM were confirmed following surgical resection. Statistical analyses were done with R (R Foundation for Statistical Computing, Vienna, Austria). Average ADC values corresponding to epithelioid- and sarcomatoid-predominant tumors were compared. ADC thresholding was accomplished by recursive partitioning and confirmed with ROC analysis. Eighty-four patients with biphasic PM's, 69 (82 %) epithelioid-predominant (BE) and 15(18 %) sarcomatoid-predominant (BS) tumors were evaluated. Thirty-eight (45 %) patients underwent extrapleural pneumonectomy (EPP), 39 (46 %) had extended pleural decortication (ePDC) and 7 (8 %) had pleural decortication (PDC). ADC values ranged between 0.696 x 10-3 to 1.921 x 10-3 mm2/s. BE tumors demonstrated significantly higher ADC values than BS tumors (p = 0.026). ADC values above 0.94 x 10-3 mm2/s were associated with a significant increase of relative risk of being in group BE over group BS (relative risk: 1.47, 95 %CI: 1.05–2.06, p = 0.027) Average ADC values of BE tumors were higher than BS tumors and the two groups can be separated by a cut off value of 0.94 X 10-3 mm2/s. [ABSTRACT FROM AUTHOR]

• Harmonizing imaging practices will allow for well-informed decisions in oncology. • Imaging technology impacts surgical approaches and will shape future treatments. • 4D MRI can assess diaphragm function in the presence of malignant pleural effusion. • AI may predict outcome and aid treatment selection to improve precision oncology. • Perfusion MRI will benefit from automated reporting for early contrast enhancement. • Dedicated evaluation criteria for peritoneal metastases will aid drug development. Imaging continues to gain a greater role in the assessment and clinical management of patients with mesothelioma. This communication summarizes the oral presentations from the imaging session at the 2023 International Conference of the International Mesothelioma Interest Group (iMig), which was held in Lille, France from June 26 to 28, 2023. Topics at this session included an overview of best practices for clinical imaging of mesothelioma as reported by an iMig consensus panel, emerging imaging techniques for surgical planning, radiologic assessment of malignant pleural effusion, a radiomics-based transfer learning model to predict patient response to treatment, automated assessment of early contrast enhancement, and tumor thickness for response assessment in peritoneal mesothelioma. [ABSTRACT FROM AUTHOR]

[Display omitted] Improving surgical resection outcomes for locally aggressive tumors is key to inducing durable locoregional disease control and preventing progression to metastatic disease. Macroscopically complete resection of the tumor is the standard of care for many cancers, including breast, ovarian, lung, sarcoma, and mesothelioma. Advancements in cancer diagnostics are increasing the number of surgically eligible cases through early detection. Thus, a unique opportunity arises to improve patient outcomes with decreased recurrence rates via intraoperative delivery treatments using local drug delivery strategies after the tumor has been resected. Of the current systemic treatments (e.g., chemotherapy, targeted therapies, and immunotherapies), immunotherapies are the latest approach to offer significant benefits. Intraoperative strategies benefit from direct access to the tumor microenvironment which improves drug uptake to the tumor and simultaneously minimizes the risk of drug entering healthy tissues thereby resulting in fewer or less toxic adverse events. We review the current state of immunotherapy development and discuss the opportunities that intraoperative treatment provides. We conclude by summarizing progress in current research, identifying areas for exploration, and discussing future prospects in sustained remission. [ABSTRACT FROM AUTHOR]

Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma is a rare and lethal cancer caused by exposure to asbestos. The highly inflammatory environment caused by fibers accumulation forces cells to undergo profound adaptation to gain survival advantages. Prioritizing the synthesis of essential transcripts is an efficient mechanism coordinated by multiple molecules, including long non-coding RNAs. Enhancing the knowledge about these mechanisms is an essential weapon in combating mesothelioma. Linc00941 correlates to bad prognosis in various cancers, but it is reported to partake in distinct and apparently irreconcilable processes. In this work, we report that linc00941 supports the survival and aggressiveness of mesothelioma cells by influencing protein synthesis and ribosome biogenesis. Linc00941 binds to the translation initiation factor eIF4G, promoting the selective protein synthesis of cMYC, which, in turn, enhances the expression of key genes involved in translation. We analyzed a retrospective cohort of 97 mesothelioma patients' samples from our institution, revealing that linc00941 expression strongly correlates with reduced survival probability. This discovery clarifies linc00941's role in mesothelioma and proposes a unified mechanism of action for this lncRNA involving the selective translation of essential oncogenes, reconciling the discrepancies about its function. • Linc00941 is a negative prognostic factor for Mesothelioma patients. • Linc00941 supports cells' survival modulating protein synthesis rate. • The interaction of linc00941 with eIF4F complex regulates translation initiation. • cMyc preferential translation is fueled by linc00941. • cMyc enhances the expression of key genes involved in translation, supporting survival and aggressiveness. [ABSTRACT FROM AUTHOR]