BACKGROUND: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known.
OBJECTIVE: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020.
METHODS: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System.
RESULTS: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%).
CONCLUSIONS: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases.

BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer.
METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 μm, and fine particulate matter with a diameter < 2.5 μm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality.
RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30).
CONCLUSIONS: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.

Malignant mesothelioma and asbestos-related lung cancer are typically associated with a poor prognosis. However, it has been observed that some patients with these cancers survive significantly longer than the average survival period. While many preliminary studies have investigated factors influencing patient survival, the specific impact of asbestos exposure has not been thoroughly explored. We followed up with 546 patients with malignant mesothelioma and 902 patients with asbestos-related lung cancer, all identified as asbestos victims between 2009 and 2021. In both malignant mesothelioma and asbestos-related lung cancer, patients with occupational asbestos exposure exhibited not only shorter median survival times but also lower 3- and 5-year survival rates compared to those with environmental exposure. Additionally, a longer duration of occupational exposure and closer proximity to the source of asbestos were linked to shorter survival times and lower survival rates. Among the patients with occupational asbestos exposure, the highest hazard ratios (HRs) were observed in those who worked in the production of asbestos-containing products across both cancer types. In contrast, significant HRs were only noted in mesothelioma patients who lived near asbestos industries, slate houses, and redevelopment areas, within the environmentally exposed group.

Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends.
Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM-EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023.
Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011.
The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011.

Asbestos-related diseases still represent a major public health problem all over the world. Among them, malignant mesothelioma (MM) is a poor-prognosis cancer, arising from the serosal lining of the pleura, pericardium and peritoneum, triggered by asbestos exposure. Literature data suggest the key role of iron metabolism in the coating process leading to the formation of asbestos bodies, considered to be both protective and harmful. Two sample sets of individuals were taken into consideration, both residing in Broni or neighboring cities (Northwestern Italy) where an asbestos cement factory was active between 1932 and 1993. The present study aims to compare the frequency of six SNPs involved in iron trafficking, previously found to be related to protection/predisposition to MM after asbestos exposure, between 48 male subjects with documented asbestos exposure who died of MM and 48 male subjects who were exposed to asbestos but did not develop MM or other neoplastic respiratory diseases (Non-Mesothelioma Asbestos Exposed - NMAE). The same analysis was performed on 76 healthy male controls. The allelic and genotypic frequencies of a sub-group of 107 healthy Italian individuals contained in the 1000 genomes database were considered for comparison. PCR-multiplex amplification followed by SNaPshot mini-sequencing reaction was used. The findings presented in this study show that the allelic and genotypic frequencies for six SNP markers involved in iron metabolism/homeostasis and the modulation of tumor microenvironment are not significantly different between the two sample sets of MM and NMAE. Therefore, the SNPs here considered do not seem to be useful markers for individual susceptibility to mesothelioma. This finding is not in agreement with previous literature.

UNASSIGNED: The aim of this study is to analyze the prevalence of somatic mutations in BRCA1 and BRCA2 in malignant mesothelioma and their putative impact on protein properties.
UNASSIGNED: Eighteen cases of malignant mesothelioma were retrieved from the archives and for next generation sequencing analysis of BRCA1 and BRCA2 genes. Variants were analyzed using Ensembl VEP17, Polyphen 2.0 software, SIFT software, MutpredV2, and SWISS-MODEL homology-modeling pipeline server.
UNASSIGNED: BRCA2 variants were found in significantly higher percentage (22%) of cases (p=0.02). Five missense variants were identified. These were p.A2351P, p.T2250A, p.A895V, pG1771D, and p.R2034C. The SIFT scores of all except one were ≥ 0.03. The Polyphen scores of these four alterations were ≤0.899. In case of p.A2315, the SIFT score was 0.01, while the Polyphen 2 score was 0.921. MutPred2 scores were ≤0.180 for all. Loss of intrinsic disorder was predicted (Pr=0.32, p=0.07) for p.R2034C, while gain of intrinsic disorder was predicted for p.A2351P (Pr=0.36, p=0.01) and p.G1771D (Pr=0.34, p=0.02).
UNASSIGNED: BRCA2 somatic variants were identified in 22% cases of malignant mesotheliomas in this study. The variants localize more frequently to the disordered regions of the protein and are predicted to affect the level of disorder.

BACKGROUND: The primary objective of this phase I, open-label trial was to assess safety and tolerability of tremelimumab monotherapy and combination therapy with durvalumab in Japanese patients with advanced cancer. Tremelimumab is a fully human monoclonal antibody against CTLA-4 in clinical trials; durvalumab is a monoclonal antibody against PD-L1 for the treatment of bladder and lung cancer.
METHODS: In part 1, tremelimumab 3 or 10 mg/kg was given every 4 weeks (Q4W) for 6 doses, and thereafter every 12 weeks until discontinuation (n = 8); subsequently tremelimumab 10 mg/kg Q4W for 6 doses/Q12W and thereafter until discontinuation was administered in 41 patients with malignant pleural or peritoneal mesothelioma (MPM). In part 2, tremelimumab 10 mg/kg (Q4W for 6 doses followed by Q12W for 3 doses) was given in combination with durvalumab 15 mg/kg (Q4W for 13 doses) in cohort 1 (n = 4). In cohort 2 (n = 6), tremelimumab 1 mg/kg (Q4W for 4 doses) was given in combination with durvalumab 20 mg/kg (Q4W for 4 doses followed by 10 mg/kg Q2W for 22 doses), while in cohort 3 (n = 6), fixed-dose tremelimumab 75 mg Q4W for 4 doses plus durvalumab 1500 mg Q4W for 13 doses was given.
RESULTS: In part 1, no dose-limiting toxicities (DLTs) for tremelimumab 3 or 10 mg/kg (Q4W for 6 doses/Q12W thereafter until discontinuation) were observed. Six (75%) patients reported treatment-related adverse events (trAEs). In the MPM dose-expansion cohort, 38 (92.7%) patients reported trAEs. In part 2, one DLT (Grade 4 myasthenia gravis) was reported for tremelimumab 10 mg/kg (Q4W for 6 doses/Q12W for 3 doses) plus durvalumab 15 mg/kg (Q4W for 13 doses). One DLT (Grade 4 hyperglycemia) was reported for tremelimumab 75 mg (Q4W for 4 doses) plus durvalumab 1500 mg (Q4W for 13 doses). Fourteen (87.5%) patients reported trAEs. Tremelimumab demonstrated low immunogenicity; 1 (16.7%) patient developed antidrug antibodies.
CONCLUSIONS: Tremelimumab 10 mg/kg (Q4W/Q12W), tremelimumab 1 mg/kg (Q4W) plus durvalumab 20 mg/kg (Q4W/10 mg/kg Q2W), and fixed-dose tremelimumab 75 mg (Q4W) plus durvalumab 1500 mg (Q4W) were safe and tolerable.ClinicalTrials.gov Identifier: NCT02141347 (https://clinicaltrials.gov/ct2/show/NCT02141347).

OBJECTIVE: Malignant mesothelioma (MM), being a rare and aggressive carcinoma, can barely be cured. Incidence of this cancer will keep climbing up in the next few decades since its major carcinogen, asbestos, is still in use in many countries. Unfortunately, prognosis of MM is unsatisfactory principally due to poor early diagnosis as a result of its long latency period and ambiguous symptoms. Lipids are known to contribute to cellular structure, signaling, and energy storage, and are widely reported to be related with tumorigenesis. Therefore, we aim to discover novel lipid biomarkers by plasma-based lipidomics that may improve MM diagnosis.
METHODS: Plasma samples from 25 MM patients and 32 healthy controls (HCs) were collected and analysed using a high-throughput liquid chromatography-mass spectrometry (LC-MS). Univariate and multivariate analyses were subsequently performed to visualize the separation trend between two groups and to screen for differential feature ions. Ions were annotated using LipidSearch 4.2 and their enriched pathways were detected on LIPEA. Receiver operating characteristic (ROC) curves were used for analysing each annotated lipid\'s diagnostic value. Survival analyses were performed to investigate each lipid\'s prognostic value.
RESULTS: In supervised partial least squares discriminant analysis (PLS-DA), clear separation between MM and HC groups was observed. A total of 34 differential lipids were annotated, among which 5 upregulated and 29 downregulated. Levels of plasma triacylglycerols (TGs) were higher in smoking versus non-smoking patients, and lower in female versus male patients. The top six lipids possessing highest diagnostic value included two phosphatidylethanolamines (PEs), two phosphatidylcholines (PCs) and two ceramides. Moreover, elevated circulating TG levels were associated with poorer survival, whereas increased monohexosylceramide (Hex1Cer) might be beneficial.
CONCLUSIONS: Our study revealed differentially expressed lipid patterns in MM compared to HC. PC, PE, and ceramides showed outstanding diagnostic performance, while TG and Hex1Cer exhibited significant prognostic values. Nevertheless, more studies should verify these trends as well as further investigating on underlying mechanisms.

UNASSIGNED: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study.
UNASSIGNED: The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest).
UNASSIGNED: The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths.
UNASSIGNED: The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.

Asbestos has been recognized as a human carcinogen associated with malignant mesothelioma, cancers of lung, larynx, and ovary. However, a putative association between gastric cancer and asbestos exposure remains controversial. In this study, we aimed to explore gastric cancer risk of workers potentially exposed to asbestos in Taiwan. The asbestos occupational cohort was established from 1950 to 2015 based on the Taiwan Labor Insurance Database, and Taiwan Environmental Protection Agency regulatory datasets, followed by the Taiwan Cancer Registry for the period 1980-2015. Standardized incidence ratios (SIRs) for cancer were computed for the whole cohort using reference rates of the general population, and also reference labor population. Compared with the general population, SIR of the asbestos occupational cohort for the gastric cancer increased both in males (1.05, 95% confidence interval (CI): 1.02-1.09) and females (1.10, 95% CI: 1.01-1.18). A total of 123 worksites were identified to have cases of malignant mesothelioma, where increased risk for gastric cancer was found with a relative risk of 1.76 (95% CI: 1.63-1.90). This 35-year retrospective cohort study of asbestos-exposed workers in Taiwan may provide support for an association between occupational exposure to asbestos and gastric cancer.