bims-mesote Biomed News
on Mesothelioma
Issue of 2022–02–06
thirteen papers selected by
Laura Mannarino, Humanitas Research
  1. Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review.
  2. Level of mesothelin expression can indicate the prognosis of malignant pleural mesothelioma.
  3. Salvage Surgery after Immunotherapy in Refractory Malignant Pleural Mesothelioma.
  4. Diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma: a systematic review and meta-analysis.
  5. Fully automated volumetric measurement of malignant pleural mesothelioma by deep learning AI: validation and comparison with modified RECIST response criteria.
  6. Prognostic value of maximum standard uptake value, metabolic tumour volume, and total lesion glycolysis of 18F-FDG PET/CT in patients with malignant pleural mesothelioma: a systematic review and meta-analysis.
  7. Immunotherapy for mesothelioma: Moving beyond single immune check point inhibition.
  8. Dosimetric evaluation of helical tomotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma: a planning study for dose escalation.
  9. Beta-carotene exerted anti-proliferative and apoptotic effect on malignant mesothelioma cells.
  10. Perioperative Anaesthesiological Management of Malignant Pleural Mesothelioma Patients Undergoing Extrapleural Pneumonectomy (EPP) and Extended Pleurectomy/Decortication ((E)PD).
  11. BAP1 germline variants in Finnish patients with malignant mesothelioma.
  12. Old Habits Die Hard - Asbestos Exposure.
  13. Mortality of workers employed in refractory ceramic fiber manufacturing: An update.
  1. Precis Cancer Med. 2021 Sep;pii: 27. [Epub ahead of print]4
    Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review.
    Alicia A Zolondick, Giovanni Gaudino, Jiaming Xue, Harvey I Pass, Michele Carbone, Haining Yang.
       Objective: The aim of this review is addressing the mechanisms of asbestos carcinogenesis, including chronic inflammation and autophagy-mediated cell survival, and propose potential innovative therapeutic targets to prevent mesothelioma development or improve drug efficacy by reducing inflammation and autophagy.
    Background: Diffuse malignant pleural mesothelioma is an aggressive cancer predominantly related to chronic inflammation caused by asbestos exposure. Millions of individuals have been exposed to asbestos or to other carcinogenic mineral fibers occupationally or environmentally, resulting in an increased risk of developing mesothelioma. Overall patient survival rates are notably low (about 8-14 months from the time of diagnosis) and mesothelioma is resistant to existing therapies. Additionally, individuals carrying inactivating germline mutations in the BRCA-associated protein 1 (BAP1) gene and other genes are predisposed to developing cancers, prevalently mesothelioma. Their risk of developing mesothelioma further increases upon exposure to asbestos. Recent studies have revealed the mechanisms and the role of inflammation in asbestos carcinogenesis. Biomarkers for asbestos exposure and malignant mesothelioma have also been identified. These findings are leading to the development of novel therapeutic approaches to prevent or delay the growth of mesothelioma.
    Methods: Review of full length manuscripts published in English from January 1980 to February 2021 gathered from PubMed.gov from the National Center of Biotechnology Information and the National Library of Medicine were used to inform this review.
    Conclusion: Key regulators of chronic inflammation mediate asbestos-driven mesothelial cell transformation and survival through autophagic pathways. Recent studies have elucidated some of the key mechanisms involved in asbestos-induced chronic inflammation, which are largely driven by extracellular high mobility group box 1 (HMGB1). Upon asbestos exposure, mesothelial cells release HMGB1 from the nucleus to the cytoplasm and extracellular space, where HMGB1 initiates an inflammatory response. HMGB1 translocation and release also activates autophagy and other pro-survival mechanisms, which promotes mesothelioma development. HMGB1 is currently being investigated as a biomarker to detect asbestos exposure and to detect mesothelioma development in its early stage when therapy is more effective. In parallel, several approaches inhibiting HMGB1 activities have been studied and have shown promising results. Moreover, additional cytokines, such as IL-1β and TNF-α are being targeted to interfere with the inflammatory process that drives mesothelioma growth. Developing early detection methods and novel therapeutic strategies is crucial to prolong overall survival of patients with mesothelioma. Novel therapies targeting regulators of asbestos-induced inflammation to reduce mesothelioma growth may lead to clinical advancements to benefit patients with mesothelioma.
    Keywords:  IL-1β; Mesothelioma; asbestos; autophagy; high mobility group box 1 (HMGB1); inflammation
    DOI:  https://doi.org/10.21037/pcm-21-12
  2. Transl Cancer Res. 2020 Dec;9(12): 7479-7485
    Level of mesothelin expression can indicate the prognosis of malignant pleural mesothelioma.
    Feifei Feng, Huanan Zhang, Ying Zhang, Hui Wang.
       Background: Malignant pleural mesothelioma (MPM) is a fatal, treatment-resistant tumor. The median survival of MPM is 9-12 months and its early prognostic markers remains uncertain. The objective of this study was to determine that the level of mesothelin expression can be as a predictor of prognosis in MPM patients.
    Methods: Level of mesothelin expression was detected in 38 MPM tissue specimens by immunohistochemistry analysis. The relationship of MPM prognosis and mesothelin expression was evaluated by univariate and multivariate Cox regression, Kaplan-Meier survival curves.
    Results: High level of mesothelin expression was significantly associated with non-epithelioid type of MPM and smoking. Meanwhile, higher level of mesothelin expression indicated a shorter total survival.
    Conclusions: The present study suggested that mesothelin is a dependent prognostic factor in MPM patients and might be a novel potential target for immunotherapy in MPM.
    Keywords:  Malignant pleural mesothelioma (MPM); mesothelin; prognosis; survival
    DOI:  https://doi.org/10.21037/tcr-19-2027
  3. Ann Thorac Surg. 2022 Jan 29. pii: S0003-4975(22)00127-8. [Epub ahead of print]
    Salvage Surgery after Immunotherapy in Refractory Malignant Pleural Mesothelioma.
    Kian C Banks, Mihir J Chaudhary, Diana S Hsu, Colin M Mooney, Jeffrey B Velotta.
      A 78-year old male presenting with epithelial malignant pleural mesothelioma (MPM) underwent multidisciplinary review at our institution. We offered surgical resection with adjuvant chemotherapy, but the patient declined. After six months, his disease progressed and he opted for dual immunotherapy with ipilimumab and nivolumab, however, after treatment initiation, he developed pneumonitis. Immunosuppression controlled the pneumonitis, but his MPM progressed, so salvage surgical resection was offered. Left extrapleural pneumonectomy was successfully performed with an unremarkable recovery. Final pathology revealed stage III biphasic mesothelioma. This is the first report to demonstrate feasibility of salvage resection for progression of MPM after immunotherapy.
    DOI:  https://doi.org/10.1016/j.athoracsur.2022.01.011
  4. Transl Cancer Res. 2021 Apr;10(4): 1856-1862
    Diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma: a systematic review and meta-analysis.
    Lei Zhang, Qianghua Zhou, Yan-Qiu Han, Peng Li, Pei-Heng Ouyang, Mei-Ying Wang, Zhi-De Hu.
       Background: Circulating microRNAs are novel diagnostic markers for various types of cancer. Several studies have investigated the diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma (MPM), but the results varied. Therefore, we performed a systematic review and meta-analysis to investigate the diagnostic value of circulating miR-126 for MPM.
    Methods: The PubMed database was searched to identify potentially eligible studies published before October 2020. The studies investigating the diagnostic value of circulating miR-126 for MPM were included in a systematic review and meta-analysis. A bivariate model was used to pool eligible studies' sensitivity and specificity. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess eligible studies' quality.
    Results: Four studies with 156 MPM patients and 459 controls were included in this systematic review and meta-analysis. The pooled diagnostic sensitivity and specificity of circulating miR-126 for MPM were 0.71 and 0.69, respectively. A high risk of bias was observed in the domains of patient selection, index test, and flow and timing.
    Conclusions: Circulating miR-126 has limited value for diagnosing MPM. Considering that the available studies have a high risk of bias, further rigorous studies are needed to assess the diagnostic value of circulating miR-126 for MPM.
    Keywords:  Malignant pleural mesothelioma (MPM); diagnosis; meta-analysis; miR-126
    DOI:  https://doi.org/10.21037/tcr-21-104
  5. Thorax. 2022 Feb 02. pii: thoraxjnl-2021-217808. [Epub ahead of print]
    Fully automated volumetric measurement of malignant pleural mesothelioma by deep learning AI: validation and comparison with modified RECIST response criteria.
    Andrew C Kidd, Owen Anderson, Gordon W Cowell, Alexander J Weir, Jeremy P Voisey, Matthew Evison, Selina Tsim, Keith A Goatman, Kevin G Blyth.
       BACKGROUND: In malignant pleural mesothelioma (MPM), complex tumour morphology results in inconsistent radiological response assessment. Promising volumetric methods require automation to be practical. We developed a fully automated Convolutional Neural Network (CNN) for this purpose, performed blinded validation and compared CNN and human response classification and survival prediction in patients treated with chemotherapy.
    METHODS: In a multicentre retrospective cohort study; 183 CT datasets were split into training and internal validation (123 datasets (80 fully annotated); 108 patients; 1 centre) and external validation (60 datasets (all fully annotated); 30 patients; 3 centres). Detailed manual annotations were used to train the CNN, which used two-dimensional U-Net architecture. CNN performance was evaluated using correlation, Bland-Altman and Dice agreement. Volumetric response/progression were defined as ≤30%/≥20% change and compared with modified Response Evaluation Criteria In Solid Tumours (mRECIST) by Cohen's kappa. Survival was assessed using Kaplan-Meier methodology.
    RESULTS: Human and artificial intelligence (AI) volumes were strongly correlated (validation set r=0.851, p<0.0001). Agreement was strong (validation set mean bias +31 cm3 (p=0.182), 95% limits 345 to +407 cm3). Infrequent AI segmentation errors (4/60 validation cases) were associated with fissural tumour, contralateral pleural thickening and adjacent atelectasis. Human and AI volumetric responses agreed in 20/30 (67%) validation cases κ=0.439 (0.178 to 0.700). AI and mRECIST agreed in 16/30 (55%) validation cases κ=0.284 (0.026 to 0.543). Higher baseline tumour volume was associated with shorter survival.
    CONCLUSION: We have developed and validated the first fully automated CNN for volumetric MPM segmentation. CNN performance may be further improved by enriching future training sets with morphologically challenging features. Volumetric response thresholds require further calibration in future studies.
    Keywords:  imaging/CT MRI; mesothelioma; pleural disease
    DOI:  https://doi.org/10.1136/thoraxjnl-2021-217808
  6. Cancer Cell Int. 2022 Feb 03. 22(1): 60
    Prognostic value of maximum standard uptake value, metabolic tumour volume, and total lesion glycolysis of 18F-FDG PET/CT in patients with malignant pleural mesothelioma: a systematic review and meta-analysis.
    Weibo Wen, Dongyuan Xu, Yongnan Piao, Xiangdan Li.
       PURPOSE: Present work systematically reviewed relevant literature based on 18F-FDG PET parameters and conducted a meta-analysis to examine the prognostic value of maximal standard uptake value (SUVmax), total lesional glycolysis (TLG), and metabolic tumour volume (MTV) in the prognosis of malignant pleural mesothelioma (MPM).
    METHODS: The relevant literature published in English were searched on PubMed, Cochrane Library, and EMBASE databases. We also evaluated the significance of SUVmax, TLG, and MTV in prognosis prediction using pooled hazard ratios (HRs).
    RESULTS: The current study comprised 12 primary studies with a total of 1307 MPM cases. According to our results, the pooled HR (95% confidence interval [CI]) of increased SUVmax for overall survival (OS) was 1.30 (95% CI 1.13-1.49, P = 0.000), whereas the increased TLG was 1.81(95% CI 1.25-2.61, P = 0.089). The increased MTV was not significantly related to OS (1.14 [95% CI 0.87-1.50, P = 0.18]).However, study design-stratified subgroup analysis suggested that differences in OS of retrospective and prospective subgroups were statistically significant, and no significant heterogeneity among different studies was observed.
    CONCLUSION: Based on the findings from the present work, PET/CT can significantly affect the prognosis prediction in MPM cases. Also, the increased SUVmax and TLG values predict an increased risk of mortality.
    Keywords:  MTV; Malignant pleural mesothelioma; Meta-analysis; PET/CT; SUVmax; TLG
    DOI:  https://doi.org/10.1186/s12935-022-02482-5
  7. Lung Cancer. 2022 Jan 25. pii: S0169-5002(22)00028-9. [Epub ahead of print]165 91-101
    Immunotherapy for mesothelioma: Moving beyond single immune check point inhibition.
    Luca Cantini, Isaac Laniado, Vivek Murthy, Daniel Sterman, Joachim G J V Aerts.
      Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with low survival rates. Platinum-based chemotherapy has represented the cornerstone of treatment for over a decade, prompting the investigation of new therapeutic strategies both in the early stage of the disease and in the advanced setting. The advent of immune check-point inhibitors (ICIs) has recently revamped the enthusiasm for using immunotherapy also in MPM. However, results from first clinical trials using single immune check-point inhibition have been conflicting, and this may be mainly attributed to the lack of specific biomarkers as well as to intra- and inter- patient heterogeneity. The phase III Checkmate743 firstly demonstrated the superiority of an ICI combination (nivolumab plus ipilimumab) over chemotherapy in the first-line treatment of unresectable MPM, leading to FDA approval of this regimen and showing that moving beyond single immune check point inhibition might be a successful strategy to overcome resistance in the majority of MPM patients. In this review, we describe the emerging immunotherapy strategies for the treatment of MPM. We also discuss how refining the approach in pre-clinical studies towards a more holistic perspective (which takes into account not only genetic but also pathophysiological vulnerabilities) and strengthening multi-institutional collaboration in clinical trials is finally helping the clinical development of immunotherapy in MPM.
    Keywords:  Chemotherapy; Combination therapy; Immune check-point inhibitors; Immune-modulation; Immunotherapy; Malignant pleural mesothelioma
    DOI:  https://doi.org/10.1016/j.lungcan.2022.01.016
  8. Transl Cancer Res. 2021 Feb;10(2): 914-922
    Dosimetric evaluation of helical tomotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma: a planning study for dose escalation.
    Fu-Li Zhang, Na Lu, Hua-Yong Jiang, Dian-Dian Chen, Ya-Di Wang.
       Background: To compare the dosimetric differences between helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT) treatment plans for inoperable malignant pleural mesothelioma (MPM).
    Methods: Ten patients with inoperable MPM were retrospectively planned with the HT and VMAT techniques, and the dose-volume histogram (DVH)-based parameters of the planning target volume (PTV) and organs at risk (OARs) were compared.
    Results: Compared with the VMAT plans, the target homogeneity index (HI) and conformity index (CI) of the HT plans were significantly better (HI: 1.04±0.01 vs. 1.11±0.03, CI: 0.80±0.07 vs. 0.71±0.12, respectively) (P<0.001, P=0.013, respectively). Regarding the OARs, including the ipsilateral lung, contralateral lung, heart, and spinal cord, the differences among the V30 (Vx: fraction of volume receiving >5, 10, 20, and 30 Gy, respectively) of the ipsilateral lung and V5, V10, and V20 of the contralateral lung were statistically significant (P=0.031, P=0.030, P=0.021, P=0.003, respectively). However, there was no significant differences between HT plans and VMAT plans, regarding the V5, V10 and V20 of the ipsilateral lung, V3 of the contralateral lung, V5 and Dmean of the heart, and Dmax of the cord. The treatment delivery time of the VMAT was significantly shorter than that of the HT (mean delivery time: 3.27±1.65 vs. 11.11±3.75 min, respectively) (P<0.001).
    Conclusions: Compared to the VMAT plans, the HT plans not only demonstrated more optimal target coverage and conformity but also considerably reduced the dose-volume parameters of the OARs in both low-dose areas in contralateral lung and high-dose areas in ipsilateral lung and contralateral lung, which is correlated to radiation injury. However, the treatment delivery time of the HT plans was longer.
    Keywords:  Helical tomotherapy (HT); dosimetric evaluation; malignant pleural mesothelioma (MPM); organs at risk (OARs); volumetric-modulated arc therapy (VMAT)
    DOI:  https://doi.org/10.21037/tcr-20-2452
  9. Naunyn Schmiedebergs Arch Pharmacol. 2022 Feb 02.
    Beta-carotene exerted anti-proliferative and apoptotic effect on malignant mesothelioma cells.
    Sedat Kacar, Ediz Sariisik, Varol Sahinturk.
      High blood levels of β-carotene and increased intake in the diets are inversely proportional to incidence of many cancer types. Antioxidant activity of β-carotene was proposed to be related with its antitumor effect. Despite this plant derivative substance being sought in many cancer types, the effectiveness of β-carotene against malignant mesothelioma remained unclear. Therefore, the present study aims to explore the impact of β-carotene on cell viability, apoptosis, and oxidative stress in mesothelioma cells. Human mesothelioma cell SPC212 were treated with β-carotene (3.125-200 μM) for 24, 48, 72, and 96 h. Cytotoxicity was measured with the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Annexin-V/propidium iodide (PI) and caspase 3/7 biomarkers were used to identify apoptotic cells. Finally, the oxidative stress was evaluated with flow cytometry. The results of the measurements indicated a significant decline in viable mesothelioma cancer cell numbers upon β-carotene treatment in time- and concentration-dependent manner when compared to control cells. Furthermore, β-carotene treatment led to apoptosis induction according to both annexin V/PI and caspase 3/7 assays. Furthermore, β-carotene increased oxidative stress in SPC212 cells. These results show how β-carotene affects proliferative, apoptotic, and oxidative properties in SPC212 malignant pleural mesothelioma cells and provide useful insights into future studies.
    Keywords:  Apoptosis; Cytotoxicity; Malignant pleural mesothelioma; SPC212; β-Carotene
    DOI:  https://doi.org/10.1007/s00210-022-02214-6
  10. Turk J Anaesthesiol Reanim. 2021 Dec;49(6): 494-499
    Perioperative Anaesthesiological Management of Malignant Pleural Mesothelioma Patients Undergoing Extrapleural Pneumonectomy (EPP) and Extended Pleurectomy/Decortication ((E)PD).
    Olivia Lauk, Corinna Von Deschwanden, Ilhan Inci, Claudio Caviezel, Isabelle Opitz, Bastian Grande.
       INTRODUCTION: Macroscopic complete resection (MCR) within a multimodality treatment concept offers currently the best survival for malignant pleural mesothelioma patients. The current standardised therapy is within a multimodality approach including (neo-)adjuvant chemotherapy followed by macroscopic complete resection (MCR). However, MCR in form of extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication ((E)PD) is correlated with significant morbidity and mortality if not performed in high volume centres as described previously according to the literature. In addition, there exist no standardised anaesthesiological protocol for this surgical approach according to the literature.
    METHODS: At our institution, diagnosed mesothelioma patients up to an International Mesothelioma Interest Group (IMIG) stage III receive induction chemotherapy followed by either EPP or (E)PD and in certain cases additional adjuvant therapy. In the period 1999-end 2019, 362 patients were intended to be treated and 303 underwent induction chemotherapy followed by MCR. MCR can be achieved either by EPP or (E)PD. Both procedures request a good teamwork between the surgeon and the anaesthesiologist.
    CONCLUSION: Although, there has been a shift lately from EPP towards lung sparing procedure (E)PD, both surgical approaches are still performed to date and is a challenging procedure for both, the surgeon as well as the anaesthesiologist. Herewith, we present our institutional perioperative standard operating procedures for the surgical and anaesthesiological management of EPP or (E)PD according to international terms of reference.
    DOI:  https://doi.org/10.5152/TJAR.2021.1108
  11. Lung Cancer. 2022 Jan 24. pii: S0169-5002(22)00029-0. [Epub ahead of print]165 102-107
    BAP1 germline variants in Finnish patients with malignant mesothelioma.
    Pauliina Repo, Aleksandra Staskiewicz, Eva Sutinen, Mikko Rönty, Tero T Kivelä, Marjukka Myllärniemi, Joni A Turunen.
       OBJECTIVES: Although asbestos exposure is the most common cause of malignant mesothelioma (MM), an aggressive cancer of the pleura or peritoneum, up to 7% of patients harbor a genetic predisposition to MM. Pathogenic germline variants in the BRCA1-associated protein 1 (BAP1) gene cause a dominantly inherited tumor predisposition syndrome, BAP1-TPDS, in which MM is the second most common associated cancer. Other frequent cancers in BAP1-TPDS are uveal melanoma (UM), cutaneous melanoma and renal cell carcinoma. Additionally patients can exhibit benign skin lesions, BAP1-inactivated nevi (BIN). Most BINs arise sporadically, but patients with BAP1-TPDS may harbor multiple BINs before other tumors or as the only indication of the syndrome. Our objective was to establish the frequency of pathogenic germline BAP1 variants in Finnish patients with MM.
    MATERIALS AND METHODS: 56 DNA samples archived in the Helsinki Biobank from Finnish patients with MM were sequenced for germline BAP1 variations. Formalin fixed paraffin embedded nevi from a pathogenic variant carrier were subjected to immunohistochemistry and exome sequencing.
    RESULTS: Sanger sequencing identified one patient with Finnish founder mutation c.1780_1781insT, p.(G549Vfs*49) in BAP1. The carrier was diagnosed with MM over fifteen years before the cohorts mean onset age (mean 68, range 27 to 82) although the patient had no asbestos exposure or family history of BAP1-TPDS. However, the patient had three BINs removed prior to the MM. The c.1780_1781insT is now found from five Finnish BAP1-TPDS families with unknown common ancestor.
    CONCLUSION: The frequency of pathogenic germline BAP1 variants in Finnish patients with MM is 1.8 % (95 % CI, 0.04 to 9.2), comparable to the frequency in Finnish patients with UM (1.9 %). The frequency of recurring BINs in patients with BAP1-TPDS should be studied further and genetic testing for BAP1 variants considered if the patient has ≥ 2 BAP1-TPDS core tumors, including BINs.
    Keywords:  BAP1; BAP1-TPDS; BAP1-inactivated nevus; Malignant mesothelioma; Tumor predisposition
    DOI:  https://doi.org/10.1016/j.lungcan.2022.01.017
  12. Turk Thorac J. 2021 Sep;22(5): 381-385
    Old Habits Die Hard - Asbestos Exposure.
    Barış Çil, Mehmet Reşit Polat, Mehmet Kabak.
       OBJECTIVE: Although the damages to health that are caused by asbestos exposure are known, the mineral continues to be in use. Our main purpose in the study was to determine the relationship between awareness and asbestos use.
    MATERIAL AND METHODS: A total of 100 residents from the Armutova village of Ergani District in the Diyarbakir province of Turkey, with previous asbestos exposure were studied between January 2010 and December 2010. Exposure to asbestos was questioned in all participants. Asbestos doses were measured in the setting where they lived. The pulmonary function tests (PFTs) including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were performed, and chest radiography was taken.
    RESULTS: The duration of asbestos exposure was found to be associated with reduced PFTs and the pathological lung findings on radiology. Although 97% of the participants were aware of asbestos and its health risks, the rates of its use were significantly higher, and associated with excessive exposure levels. Longer duration of asbestos exposure was significantly associated with reduced FVC. There were more prominent reductions in FEV1 with longer durations of asbestos exposure.
    CONCLUSION: The high rates of asbestos use indicate that changing habits, particularly among individuals residing in rural areas, is difficult. In our country, the main route of asbestos exposure is through the environment, which is at least as hazardous as occupational exposure.
    DOI:  https://doi.org/10.5152/TurkThoracJ.2021.0280
  13. J Appl Toxicol. 2022 Jan 31.
    Mortality of workers employed in refractory ceramic fiber manufacturing: An update.
    Grace LeMasters, James E Lockey, Timothy J Hilbert, Jeff W Burkle, Carol H Rice.
      This study evaluates the possible association between refractory ceramic fibers (RCF) exposure and all causes of death. Current and former employees (n=1,119) hired from 1952-1999 at manufacturing facilities in New York (NY) state and Indiana were included. Work histories and quarterly plant-wide sampling from 1987-2015 provided cumulative fiber exposure (CFE) estimates. The full cohort was evaluated as well as individuals with lower and higher exposure, <45 and >45 fiber-months/cc. The Life-Table-Analysis-System was used for all standardized mortality estimates (SMR). Person-years at risk accumulated from start of employment until 12/31/2019 or date of death. There was no significant association with all causes, all cancers, or lung cancer in any group. In the higher exposed there was a significant elevation in both malignancies of the "urinary organs" (SMR=3.59, 95% CI 1.44, 7.40), and "bladder or other urinary site" (SMR=4.04, 95% CI 1.10, 10.36) which persisted in comparison to regional mortality rates from NY state and Niagara County. However, six of the nine workers with urinary cancers were known smokers. In the lower exposed there was a significant elevation in malignancies of the lymphatic and hematopoietic system (SMR=2.54, 95% CI 1.27, 4.55) and leukemia (SMR=4.21, 95% CI 1.69, 8.67). There was one pathologically unconfirmed mesothelioma death. A second employee currently living with a pathologically confirmed mesothelioma was identified, but the SMR was non-significant when both were included in the analyses. The association of these two mesothelioma cases with RCF exposure alone is unclear because of potential past exposure to asbestos.
    Keywords:  Man-Made Vitreous Fibers; Refractory Ceramic Fibers; Synthetic Vitreous Fibers; bladder; cancer; lung; mesothelioma; urinary
    DOI:  https://doi.org/10.1002/jat.4295
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