Mesothelioma Research Articles

The efficacy and safety of anlotinib combined with chemotherapy in treatment of advanced soft tissue sarcoma

BackgroundTo evaluate the efficacy and safety of anlotinib combined with chemotherapy in the treatment of advanced soft tissue sarcoma (STS).MethodsA total of 14 patients with advanced STS consisting of 4 liposarcoma, 3 undifferentiated polymorphous sarcoma, 2 synovial sarcoma, 1 Extraosseous ewing sarcoma, 1 spindle cell sarcoma, 1 Sarcomatoid malignant mesothelioma, 1 hemangiosarcoma, and 1 fibrosarcoma, were treated with anlotinib plus chemotherapy. The anlotinib was combined with chemotherapy as the first-line treatment in 13 patients, and as second-line treatment in 1 patient. Chemotherapy regimens were based on anthracyclines and ifosfamide, and other drugs included paclitaxel, and so on. Efficacy and safety were evaluated every 2 treatment cycles.ResultsAccording to the stage of AJCC, 9 patients were stage III and 5 patients were stage IV. The average cycle of treatment is 3.86. Among the 14 patients, 2 cases had received surgical treatment after neoadjuvant chemothrapy, 5 cases had partial response (PR), 7 cases had stable disease (SD), and 2 cases had progressive disease (PD). The overall response rate (ORR) was 35.7% (5/14). Patients who had not underwent surgical treatment were with a disease control rate (DCR) of 83.3% (10/12). The median progression free survival (PFS) was 8.25 months. The common treatment-related adverse effects included bone marrow suppression, nausea, vomiting and hypertension. Three patients had severe adverse effect, which was febrile neutropenia. No treatment-related death was found.ConclusionsAnlotinib combined with chemotherapy in the treatment of STS is effective and tolerable, which is a promising strategy. It is worthy of further clinical research.

Asbestos is still paid for dearly

Abstract Background In Italy, asbestos is a current and important problem in terms of health effects due to the long latency of diseases related to its exposure. The aim of the study is to analyze the case history of malignant pleural mesothelioma (MPM) in the University Hospital of Siena in the period 2019-2023, comparing the type of exposure (occupational/non-occupational), the mean conventional latencies (MCL) of diagnosis, the histotype and the most exposed categories. Methods The study was conducted from January to April 2024, on 69 patients (79.7% male and 20.3% female) with a diagnosis of pleural mesothelioma between 2019 and 2023. 48 patients lived in Tuscany and 21 outside the region. The data were collected by consulting the medical surveillance records and radiological images through the VuePacs platform, then organized in a filtered database. Results Of 69 patients, exposure was occupational in 54 cases and non-occupational in the remaining 15. In patients with occupational exposure, the MCL was 55.9 years and the mean age at diagnosis was 73.66 years; in the other group, the MCL was 47.3 years and the mean age at diagnosis was 66.8. The study revealed the prevalence of epithelioid histotype in 76.81% of cases, biphasic in 15.94% of cases and sarcomatoid in 7.25%. The most at-risk categories were: metalworking (10 cases), construction (8), electricity/gas production (6) and shipyards (4). The study also identified two cases of atypical occupational exposure. Conclusions The shorter average latency in cases with non-occupational exposure is in accordance with the current scientific literature, as well as the prevalence of epithelioid histotype. Are hereby confirmed the primary role of health surveillance in the in-depth investigation of occupational anamnesis and of the environmental sites’ survey as prevention tool, especially in those cases of MPM whose evaluation, deviating from the exposure standards, could lead to the assignment of a misdiagnosed exposure. Key messages • The effects of asbestos exposure are a current and important problem in our country, even after its disposal, due to the long latency of disease onset. • In-Department investigation of occupational anamnesis and survey of environmental sites as prevention tool play an essential role in MPM evaluation, especially in those cases of atypical exposure.

Surgical and oncological outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma : Aretrospective single center experience.

Peritoneal mesothelioma (PM) is arare disease with various histopathological subtypes. For malignant peritoneal mesothelioma and borderline subgroups locoregional therapy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been implemented. The aim of our study was to retrospectively present the outcome after CRS and HIPEC for patients with different subtypes of peritoneal mesothelioma. In total 15patients received CRS and HIPEC due to peritoneal mesothelioma at our tertiary referral hospital between 2013 and 2022. Surgical and oncologic outcomes of 14 of those patients were retrospectively evaluated as one patient was lost to follow-up. The cohort consisted of 9patients with diffuse malignant peritoneal mesothelioma (64.3%), 3patients with multicystic peritoneal mesothelioma (21.4%) and 2patients with well-differentiated peritoneal mesothelioma (14.3%). Complete cytoreduction was possible in 85.7% (n = 12). The major complication rate was 28.6% (n = 4) and the reoperation rate was 14.3% (n = 2). Median follow-up was 55months (standard error, SE 15.0%, 95% confidence interval, CI 25.6-84.4 months). Over this time period 64.3% (n = 9) had no evidence of disease, 21.4% (n = 3) were alive with disease and 14.3% (n = 2) died of peritoneal mesothelioma. The median recurrence-free survival of patients was 13months (SE13.0%, 95% CI 0.0-32.2 months). None of the patients with multicystic peritoneal mesothelioma had evidence of disease at the time of last follow-up. Patients with peritoneal mesothelioma should receive locoregional treatment as good oncological results can be achieved with reasonable postoperative morbidity. Thus, awareness is necessary for this rare but potentially aggressive disease to offer the best medical care.

An evaluation of trends for mesothelioma mortality in American women: Addressing the content of a recent Morbidity and Mortality Weekly Report (MMWR).

Mesothelioma is a fatal disease that has historically been associated with exposure to airborne asbestos. Because occupational asbestos exposures dropped dramatically in the late 1960s and early 1970s, far fewer cases of mesothelioma today are due to these fibers but, instead, are usually a result of the aging process or genetic predisposition. In May of 2022, a Morbidity and Mortality Weekly Report (MMWR) was issued by the Centers for Disease Control and Prevention (CDC) regarding malignant mesothelioma incidence in women from 1999 to 2020. While this MMWR alerted citizens to the continued presence of the disease, after reading this article one might have thought that the CDC was suggesting that the disease was increasing in women due to asbestos exposures (which it is not). In the present analysis, we investigate several factors related to the interpretation of epidemiological data for mesothelioma, including the role of asbestos as a risk factor over time. The authors conducted a review of the scientific community's understanding of mesothelioma incidence and asbestos exposures amongst women, as well as an investigation of the methods and references in the MMWR article. Although various articles have recently discussed the incidence of both peritoneal and pleural mesothelioma in women, it is fortunate that the age-adjusted rates for mesothelioma have remained flat (neither increased nor decreased significantly) in women for the past 50 years. Incredibly few women in the U. S. have had appreciable cumulative exposures to any type of asbestos (chrysotile, amosite, or crocidolite) in the workplace or from the ambient environment, especially since about 1965-1970. In this paper, we highlight six factors that should be considered when evaluating the incidence of mesothelioma amongst American women in the current era. Without sufficient consideration of these factors, improper conclusions have been drawn over the past several years.

Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells.

The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.

Confirmatory validation of a brief patient-reported outcome measure assessing psychological distress in caregivers of malignant mesothelioma patients: the Mesothelioma Psychological Distress Tool–Caregivers

ObjectiveThe diagnosis of malignant mesothelioma (MM) can be devastating for both patients and caregivers, who may experience intense suffering from a physical, psychological, and interpersonal perspective. Despite the extensive literature on caregiver distress, there is a lack of validated measures to provide evidence of psychological distress of caregivers of MM patients. Therefore, in a previous study we developed the Mesothelioma Psychological Distress Tool–Caregivers (MPDT-C) to evaluate the specific profile of psychological distress in this population. This paper describes the item selection, factor analysis, and psychometric evaluation of the revised MPDT-C.MethodsThe analyses of this work first aimed to confirm the previous factorial structure. In the case of nonfit, it aimed to find an alternative structure and causes of nonfit in the model. Examination of the fit of the factorial model was conducted using a Bayesian approach.ResultsThe final version of the MPDT-C is a 7-item self-report questionnaire consisting of one factor (Burden for the caregiver).ConclusionHaving a short self-report questionnaire to assess the psychological distress experienced by caregivers of MM patients has several advantages. First, it is suited to epidemiological studies where multiple variables and measures are involved. Second, it is easy to administer and does not take much time to complete. Therefore, the MPDT-C can also be administered in clinical contexts, perhaps when MM patients attend follow-up medical evaluation. Lastly, short measures are less affected by cognitive fatigue, which is very common in a long battery of tests and could affect response reliability.

Synergistic Effect of Resveratrol and Paclitaxel in the Treatment of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a lethal and aggressive cancer due to exposure to asbestos since this carcinogen is still being used in industrial buildings and housing in several countries. Untreated MPM has a median survival time of 12 months, and most people die within 24 months after diagnosis. If caught early, surgery may be performed. Treatment option for palliative care is limited using platinum with pemetrexed. Malignant transformation of a cell is attributed to a series of genetic and epigenetic events involving alterations in several oncogenes, tumor suppressor genes, and others. Different anticancer and antioxidants with anticancer properties were tested individually and in combination to find the best synergistic effect in killing MSTO-211H, a lung mesothelioma cell line used as model of MPM. Once the combination was identified, assays and staining methods such as MTT, Rhodamine123, Hoechst 33342, Nuclear ID Red/Green, and Western Blot were performed to identify different proteins involved in apoptosis and cell signaling cascade to proof the cytotoxic effect of the combine anticancer and antioxidant treatment. Combination of Paclitaxel (PAC) at 3 µM and Resveratrol (RSV) at 62.5 µM showed synergistic effect on MSTO-211H cells by causing inhibition of epidermal growth factor receptor (EGFR), inhibition of mitogen activated protein kinases (MEKs) 1-4, inhibition of programmed death ligand-1 (PDL-1), inhibition of cell cycle proteins, and induction of caspases 3-8. This study provided possible potential application of using RSV as a chemo-enhancing compound with PAC in the treatment of MPM.

Bedside to bench and back again-translational research in interventional pulmonology.

Translational research in Interventional Pulmonology has made significant advances in recent years, ranging from novel biomarkers and imaging to practice-changing clinical trials in lung cancer and pleural disease. This review article aims to summarize key research studies in the field to understand the latest published evidence and to highlight areas of growing academic interest. In lung cancer, the role of novel imaging and biomarkers and their potential utility in early lung cancer diagnosis will be highlighted. In pleural disease, less invasive/conservative treatment in pneumothorax, early aggressive treatment in pleural infection along with novel biomarkers, and the shift beyond drainage strategies in malignant pleural effusion and mesothelioma will be discussed. This overview of translational research in the field of interventional pulmonology will ultimately help to highlight the gaps in current evidence to promote research in areas of clinical significance.

P4.14C.04 Exhaled Breath Analysis for the Early Diagnosis of Malignant Pleural Mesothelioma and the Surveillance of Asbestos-Exposed At-Risk Subjects

P4.14C.04 Exhaled Breath Analysis for the Early Diagnosis of Malignant Pleural Mesothelioma and the Surveillance of Asbestos-Exposed At-Risk Subjects

Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review

Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review

Soluble Mesothelin-Related Peptide as a Prognosticator in Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy

Immune checkpoint therapy (ICT) has significantly impacted malignant pleural mesothelioma (MPM) treatment. Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT. We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of MSLN and PD-L1. Both univariable and multivariable Cox regression analyses were used to determine independent prognosticators for overall survival (OS). A prospective ICT clinical trial and our historical cohort were included for validation. Seventy-seven patients (62%) were treated with either anti-PD-(L)1 monotherapy, and the remaining 38% were given combination ICT. Higher pre-ICT SMRP levels were observed in epithelioid versus non-epithelioid MPM. Serum PD-L1 levels did not show significant differences between the groups. Univariable analysis identified durable clinical benefit, development of immune-related adverse events, and SMRP levels as significantly associated with OS. Multivariable analysis confirmed SMRP as an independent prognostic factor, with lower levels (≤1.35 nmol/L) correlating with improved OS. The association of high SMRP with worse prognosis was validated in the prospective ICT clinical trial cohort and not in our historical cohort treated without ICT. SMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.

Biomarkers to predict the benefits of immune‑checkpoint blockade‑based therapy in patients with malignant peritoneal mesothelioma (Review)

Biomarkers to predict the benefits of immune‑checkpoint blockade‑based therapy in patients with malignant peritoneal mesothelioma (Review)

68Ga-FAPI PET/CT findings of diffuse malignant peritoneal mesothelioma involving the gastrointestinal tract.

68Ga-FAPI PET/CT findings of diffuse malignant peritoneal mesothelioma involving the gastrointestinal tract.

Ascites as a Rare Manifestation of Malignant Peritoneal Mesothelioma: A Case Report

Ascites as a Rare Manifestation of Malignant Peritoneal Mesothelioma: A Case Report

Asbestos: Communicating the Health Issues Derived from Fibrous Minerals to Society

Asbestos, also known by its commercial name “amianthus”, has been widely used in various industries due to its unique properties. However, the extensive use of asbestos has had serious consequences for human health, most notably asbestosis, an irreversible chronic lung disease. Asbestosis increases the risk of lung cancer and malignant mesothelioma, both of which are fatal. Applied sciences such as microscopy (optical and scanning electron microscopy) and geochemistry have been fundamental in characterizing the mineral fibers of asbestos to understand its role in human health. We previously used these techniques to characterize these fibers; in this study, we explored the issues associated with asbestos and asbestosis, as well as the challenges facing science communication strategies in effectively informing society and workers about these risks. The lack of scientific culture, in general, has led to a lack of public awareness of the risks of asbestos. As such, effective communication and outreach plans and strategies, including the visualization of the fibers to demonstrate why problems arise if inhaled, must be implemented to address these challenges. Educational campaigns, guidelines, and plans that are informative and actionable, teaching workers, communities, and the public about the risks of asbestos are crucial. A general knowledge of mineralogy and geochemistry is needed, and providing and disseminating proper scientific communication may help to close the knowledge gap. We use examples and experience from Spain and Italy to illustrate this matter, as we have been working on the characterization of ultramafic complexes in these countries for more than ten years. Additionally, because these countries have strict laws for asbestos-containing materials, they are currently involved in retiring and demolishing buildings and infrastructure that contain asbestos.

Dose-escalation, tolerability, and efficacy of intratumoral and subcutaneous injection of hemagglutinating virus of Japan envelope (HVJ-E) against chemotherapy-resistant malignant pleural mesothelioma: a clinical trial

The hemagglutinating virus of Japan envelope (HVJ-E) is an inactivated Sendai virus particle with antitumor effect and inducing antitumor immunity. However, its dosage and efficacy have not been verified. We conducted a phase I clinical study on chemotherapy-resistant malignant pleural mesothelioma (MPM) aiming to determine the recommended dosage for a phase II study through dose-limiting toxicity and evaluate HVJ-E’s preliminary efficacy. HVJ-E was administered intratumorally and subcutaneously to the patients with chemotherapy-resistant MPM. While no serious adverse events occurred, known adverse events of HVJ-E were observed. In the preliminary antitumor efficacy using modified response evaluation criteria in solid tumors (RECIST) criteria, three low-dose patients exhibited progressive disease, while all high-dose patients achieved stable disease, yielding disease control rates (DCRs) of 0% and 100%, respectively. Furthermore, the dose-dependent effect of HVJ-E revealed on DCR modified by RECIST and the baseline changes in target lesion size (by CT and SUL-peak; p < 0.05). Comparing targeted lesions receiving intratumoral HVJ-E with non-injected ones, while no clear difference existed at the end of the study, follow-up cases suggested stronger antitumor effects with intratumoral administration. Our findings suggest that HVJ-E could be safely administered to patients with chemotherapy-resistant MPM at both study doses. HVJ-E exhibited some antitumor activity against chemotherapy-resistant MPM, and higher doses tended to have stronger antitumor effects than lower doses. Consequently, a phase II clinical trial with higher HVJ-E doses has been conducted for MPM treatment. Trial registration number: UMIN Clinical Trials Registry (#UMIN000019345).

Practical Approach to Reporting Based on the International System for Serous Fluid Cytopathology.

The International System for Serous Fluid Cytopathology (TIS) is intended for reporting cytological specimens from serous cavities: pleural, abdominal and pericardial cavities. TIS is being adopted into practice in cytology laboratories worldwide. In this system, there are six diagnostic categories: non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, malignant-primary and malignant-secondary. Malignant-primary category almost always implies malignant mesothelioma and malignant-secondary usually refers to metastasis from carcinoma but also to involvement of serous cavity by haematolymphoid and other malignancies. When evaluating effusion cytological specimen adequacy, the factors that must be considered are sample volume, cellular content and cellular preservation. In the diagnostic analysis and interpretation, it is helpful to consider systematically all basic cytomorphological components in a sample. The basic components are architecture, cell populations, cell size, cytoplasm, nuclei and background elements. One important requirement for a successful evaluation of an effusion cytological specimen is sufficient clinical and radiological information in a referral. Clinical information may guide ancillary testing. In the present review, we provide a practical and educational approach to reporting serous effusion cytology based on the TIS.

Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment

ObjectivesOn the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi/nivo) has become a standard-of-care. Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi/nivo on the basis of MAPS2 results. Here we report on real-world survival and safety outcomes of ipi/nivo for patients with MPM in Switzerland. MethodsTwelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators. ResultsOf the 109 patients with MPM treated with ipi/nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi/nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, p < 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi/nivo treatment occurred in 65 patients (62%). The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients. ConclusionIn this real-world cohort of patients with MPM treated with ipi/nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

P2.14A.13 Discovery and Clinical Application of Potential Prognostic Genes for Clinical Outcome in Malignant Pleural Mesothelioma

P2.14A.13 Discovery and Clinical Application of Potential Prognostic Genes for Clinical Outcome in Malignant Pleural Mesothelioma

Characteristics of long-term survivors with malignant pleural mesothelioma

Pleural mesothelioma (PM) is a cancer with usually a dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centres around the world. This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival ≥ 5 years from surgery) treated within a multimodality therapy approach including macroscopic complete resection. Overall survival was calculated with Kaplan Meier analysis and cases were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis. There were 276 long-term survivors, most were male (n=166, 63%) with a median age of 59 (range 21-83) years at time of diagnosis. The histology for 246 was epithelioid and non-epithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients were dead, 104 were alive and 10 were lost to follow-up. Pathological tumor stages were: pT1 (n=50), pT2 (n=63), pT3 (n=90) or pT4 (n=16), pN0 (n=150), pN1 (n=20) and pN2 (n=39). The matched control dataset included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, there was moderate evidence that a low white blood cell (WBC) count before surgery was more often observed in long-term survivors. The data show that long-term survival in PM is possible in a subgroup of surgically treated patients; histological subtype and WBC count seem to be prognosticators for longer survival.