Thoracic Cancer

About the journal

Publisher: Wiley Publishing Asia Pty Ltd
Published: 2010 to the present, Singapore
Language: English
ISSN: 1759-7706 (print), 1759-7714 (electronic)
Its record in the NLM Catalog

2020s

BAP1 Loss Might Be a Predictive Biomarker for Immunotherapy Response in Pleural Mesothelioma. R. Imase, R. Sakakibara, S. Kirimura, et al. 2026;17(13):e70343. PubMed · Publisher · Free full text

Abstract

Introduction: Reliable predictive biomarkers for immune checkpoint inhibitors (ICIs) in pleural mesothelioma (PM) are lacking. Loss of BRCA1-associated protein 1 (BAP1) is a frequent molecular alteration in PM and may influence the tumor immune microenvironment. We evaluated whether BAP1 loss is associated with clinical outcomes following immunotherapy.

Methods: We retrospectively analyzed 14 patients with PM who were treated with ICIs between April 2014 and May 2024. BAP1 status was assessed by immunohistochemical staining of resected tumor specimens. Patients were categorized into BAP1-loss and BAP1-positive groups. Progression-free survival (PFS), overall survival (OS), response rate (RR), and disease control rate (DCR) were compared.

Results: BAP1 loss was observed in nine patients (64%). Median PFS was significantly longer in the BAP1-loss group compared with the BAP1-positive group (5.3 vs. 2.1 months; log-rank p = 0.03). Median OS was also prolonged in the BAP1-loss group (8.6 vs. 2.1 months; log-rank p = 0.03). RR and DCR were numerically higher among patients with BAP1 loss.

Conclusion: BAP1 loss was associated with improved clinical outcomes following immunotherapy in PM. These findings support that a molecular profile that includes BAP1 deletion may serve as a biomarker for predicting response to immunotherapy in PM.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Diverging Trajectories of Lung Cancer Burden in China, Japan, and South Korea: A Comparative Risk Assessment from the Global Burden of Disease Study 1990-2021. S. Zhao, G. Deng, D. Li, et al. 2026;17(16):e70370. PubMed · Publisher · Free full text

Abstract

Objective: Lung cancer poses a major public health challenge in East Asia. This study aimed to compare the evolving burden of lung cancer and key risk factors from 1990 to 2021 in China, Japan, and South Korea, three neighboring countries with distinct socioeconomic and public health profiles.

Methods: Using data from Global Burden of Disease Study 2021, we applied an integrated analytical framework. This included Joinpoint regression to identify trend transitions, an Age-Period-Cohort model to disentangle demographic effects, and ARIMA time-series modeling for forecasting. Risk attribution and cluster analysis assessed contributions of behavioral, environmental, occupational, and metabolic factors. Marked disparities were observed.

Results: China's age-standardized mortality rate (ASMR) increased (Estimated Annual Percentage Change, EAPC = +0.25%), while Japan (EAPC = -0.91%) and South Korea (EAPC = -1.02%) experienced declines. Smoking remained the predominant risk factor (Attribution score: 10/10), but risk profiles diverged: ambient air pollution contributed 9/10 to China's burden, occupational asbestos dominated in Japan (Score: 8/10), and metabolic risks (high fasting plasma glucose) rose sharply in South Korea (+18.4% since 1990). The burden peaked in the 65-79 age group, with male mortality 3-8 times higher than females. Projections suggest stabilization in China (ASMR ~30.5 by 2050), continued decline in Japan (~12.0), and a potential rebound risk in South Korea by 2050.

Conclusion: Lung cancer burden reflects divergent epidemiological transitions, shaped by socioeconomic development and public health policies. Precision prevention strategies are essential, prioritizing tobacco control and air quality in China, occupational risks in Japan, and metabolic factors in South Korea, supported by regional collaboration.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Effects of Autophagy Inhibition by SAR405, a Selective VPS34 Inhibitor, on Pleural Mesothelioma Cells. Y. Kuwabara, K. Sakai, K. Shiraishi, et al. 2026;17(5):e70255. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma is a highly aggressive malignancy with a poor prognosis due to the limited efficacy of currently available therapies. Macroautophagy (hereafter "autophagy") is a lysosome-mediated degradation pathway involved in cellular homeostasis that can either support or inhibit cancer progression depending on context. In this study, we investigated the effects of SAR405, an inhibitor of vacuolar protein-sorting 34 (VPS34), which is important for regulating the early stage of autophagy, on pleural mesothelioma.

Methods: Human pleural mesothelioma cell lines H28, H2452, and 211H were cultured with SAR405. The effects of SAR405 on protein expression, cell viability, colony formation, cell invasion, and the cell cycle were investigated, as were its synergistic effects with cisplatin. Autophagy induction was evaluated in mesothelioma cells transfected with the pMRX-IP-GFP-LC3-RFP-LC3ΔG plasmid, which was developed for the quantitative and statistical estimation of autophagy.

Results: SAR405 treatment alone significantly reduced cell viability, colony formation, and cell invasion, and increased G2/M cell cycle arrest. In addition, SAR405 induced apoptosis in the H2452 cell line. Although cisplatin weakly induced autophagy in mesothelioma cells, its combination with SAR405 did not result in additive or synergistic effects on cell viability.

Conclusions: Based on these results, inhibition of VPS34 by SAR405 effectively suppressed cell viability in all mesothelioma cell lines and induced apoptosis in H2452 cells. The findings of this study indicate the potential for VPS34 inhibition as a new strategy for the treatment of mesothelioma and provide insights into the complex role of autophagy in this malignancy.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Emerging Strategies in the Diagnosis and Treatment of Pleural Mesothelioma: An Overview. R. Pagliaro, B. Leonardi, A. Schiattarella, et al. 2026;17(8):e70259. Review PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is a rare and aggressive cancer arising from pleural mesothelial cells with a strong association to asbestos exposure. Among the diagnostic strategies available are noninvasive techniques including thoracic ultrasound (TUS), computed tomography (CT) scans, positron emission tomography (PET-CT), and invasive procedures such as thoracoscopy and pleural biopsy. Accurate identification of the histological subtype is critical for tailoring treatment strategies. The standard treatment for unresectable PM has traditionally been chemotherapy, particularly platinum and pemetrexed. However, recent advances in translational clinical research, including immune checkpoint inhibitors (ICIs), are changing the therapeutic landscape, offering new opportunities for personalized treatment. The recent FDA approval of nivolumab and ipilimumab combination therapy as a first-line treatment has significantly improved outcomes, especially for nonepithelioid subtypes. Ongoing studies are exploring additional immune-targeted therapies such as VISTA, LAG-3, and dendritic cell-based therapies. Early detection, refined biomarker identification, and a deeper understanding of the tumor microenvironment remain essential to improving PM prognosis and patient survival. This review provides a comprehensive exploration of the epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and molecular markers), staging, and current treatment strategies for PM.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Insights Into Genomic Drivers, Transcriptomic Heterogeneity, and Therapeutic Vulnerabilities From Novel Mesothelioma Cell Lines. Y. Wu, F. Cao, J. Dai, et al. 2026;17(15):e70366. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is an aggressive cancer with limited therapeutic options and poor prognosis, necessitating comprehensive model systems for mechanistic studies and drug discovery.

Methods: Tumor cells were isolated from malignant pleural effusion of PM patients and subjected to primary culture and continuous passaging. Cell lines were successfully established after more than 40 continuous passages in vitro. Cell identification included morphological analysis, species identification, short tandem repeat (STR) profiling, mycoplasma detection, in vitro proliferation assays, in vivo tumorigenicity testing in NOD/SCID mice, and immunohistochemical characterization. Genomic landscapes and transcriptomic profiling were defined by whole-exome, whole-genome sequencing, and RNA-sequencing.

Results: Three Chinese-derived pleural mesothelioma cell lines (PUMC-MESO1, PUMC-MESO3, and PUMC-MESO4) were successfully established. All three cell lines exhibited epithelioid morphology with adherent growth patterns. Upon subcutaneous transplantation into NOD/SCID mice, PUMC-MESO1 and PUMC-MESO4 demonstrated tumorigenicity, while PUMC-MESO3 remained non-tumorigenic after 3 months of observation. Histopathological examination confirmed their mesothelioma origin through positive staining for mesothelial markers including calretinin, WT-1, and D2-40. Genomic analysis revealed characteristic PM genomic alterations including mutations in BAP1, NF2, and TP53, along with CDKN2A deletions. Transcriptomic analyses revealed heterogeneous molecular features among the three cell lines. Although the PUMC-MESO cell lines displayed distinct clustering patterns relative to the CCLE mesothelioma cohort, each retained transcriptomic similarities to specific established mesothelioma models. Drug sensitivity assays further demonstrated heterogeneous responses to standard therapeutic agents.

Conclusion: This study reports the establishment and characterization of three novel PM cell lines. These models recapitulate key aspects of PM biology, exhibit diverse therapeutic responses, and provide a valuable new resource for investigating disease mechanisms and advancing precision oncology research.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Interleukin 32 Expression in Mesothelioma. T. Mikamo, R. Niwa, Y. Hanamatsu, et al. 2026;17(14):e70353. PubMed · Publisher · Free full text

Abstract

Background: Interleukin 32 (IL32) has context-dependent roles in carcinogenesis across cancer types. In this study, we examined IL32 in mesotheliomas.

Methods: IL32 protein expression was evaluated by immunohistochemistry in 56 mesothelioma tissue microarray specimens and by immunoblot analysis in cultured mesothelioma cell lines. The functional roles of IL32 were examined through ectopic expression of IL32β and IL32θ isoforms in D-Meso-Sonobe cells with epithelial-mesenchymal plasticity and through siRNA-mediated IL32 downregulation followed by cell-detachment-induced apoptosis assays in epithelioid mesothelioma cells.

Results: IL32 immunoreactivity was detected in 20 of 56 mesothelioma tissue specimens, including cytoplasmic staining in 20 of 39 epithelioid cases, whereas little or no immunoreactivity was found in 17 sarcomatoid cases. In immunoblot analysis, an IL32 protein band was detected in two cultured epithelioid mesothelioma cell lines (MPM-2 and TCC-Meso-1), but not in sarcomatoid MPM-1 cells. Two IL32 isoforms, IL32β and IL32θ cDNAs, were isolated from MPM-2 cells. Ectopic expression of IL32θ, but not IL32β, inhibited the morphological transition from epithelioid to sarcomatoid features in D-Meso-Sonobe mesothelioma cells with mesothelial-mesenchymal transition plasticity. Conversely, siRNA-mediated downregulation of IL32 increased cell detachment-induced apoptosis in MPM-2 and TCC-Meso-1 epithelioid mesothelioma cells. Moreover, IL32 suppressed expression of secreted protein acidic and rich in cysteine, which is an epithelial-mesenchymal transition-related protein in mesothelioma cells.

Conclusions: These findings indicate that IL32 is expressed in epithelioid mesothelioma and may contribute to mesotheliomagenesis.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Risk Factors of Hematological Toxicity of Mesothelioma Treatment-A Territory-Wide Retrospective Study. W.C. Kwok, D.Y.H. Yap, I.S.H. Leung, et al. 2026;17(2):e70243. PubMed · Publisher · Free full text

Abstract

Background: While chemotherapy remains the treatment of choice for mesothelioma, it carries significant toxicities, especially hematological toxicity.

Methods: We conducted this territory-wide retrospective study in Hong Kong to investigate the prevalence and risk factors of hematological toxicity associated with mesothelioma treatment.

Results: A total of 222 patients were included in the analysis. Lower baseline serum albumin level and more lines of cytotoxic chemotherapy received were risk factors for developing grade 3-4 hematological toxicity with aOR of 1.05 (95% CI, 1.02-1.09, p = 0.003) and 1.50 (95% CI, 1.03-2.19, p = 0.033) respectively. Risk factors for developing neutropenic fever included: diabetes mellitus (aOR = 9.44, 95% CI, 2.59-34.45, p < 0.001); the use of chemotherapy other than pemetrexed (aOR = 4.80, 95% CI, 1.05-21.89, p = 0.043); the presence of third-space fluid (aOR = 3.58, 95% CI, 1.16-11.05, p = 0.027), pleural effusion (aOR = 4.20, 95% CI, 1.34-13.17, p = 0.014) and pericardial effusion (aOR = 7.97, 95% CI, 1.18-53.93, p = 0.033). Number of lines of cytotoxic chemotherapy the patients received was the risk factor for pack cell transfusion with aOR of 2.35 (95% CI, 1.54-3.60, p < 0.001).

Conclusion: Hematological toxicities were commonly seen in the treatment course of mesothelioma. Risk factors include disease factors and treatment factors. Use of ICI could bring about hope in reducing the risk of hematological toxicities.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
A Case of Duodenal Metastasis From Malignant Pleural Mesothelioma Diagnosed by Gastrointestinal Endoscopy Following Progressive Anemia During Salvage Chemotherapy. N. Ichiyama, H. Yamane, T. Saitou, et al. 2025;16(11):e70098. Case report · Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) primarily progresses through direct invasion into the lung and pleura and is a refractory tumor in which asbestos exposure is a major underlying factor in most cases. Hematogenous metastasis of MPM is not uncommon in advanced stages, and reports suggest that metastatic sites may impact prognosis. Gastrointestinal metastases, ranging from the stomach to the colon, have been sporadically observed, but metastases to the small intestine and duodenum are exceedingly rare. Here, we report a case in which duodenal metastasis of MPM was endoscopically identified during the patient's lifetime while undergoing salvage chemotherapy following treatment with an immune checkpoint inhibitor and cytotoxic chemotherapy. Given the rarity and clinical significance of such cases, we present this report with a review of the relevant literature.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
A Multi-Center Real-World Study of Clinicopathologic Characteristics and Efficacy of the Malignant Mesothelioma in Chinese Population. C. Sun, X. Yang, L. Chen, et al. 2025;16(3):e15533. PubMed · Publisher · Free full text

Abstract

Objective: Malignant mesothelioma (MM) is a rare malignant tumor. To explore the clinicopathological characteristics and efficacy of Chinese population with MM in the real-world.

Methods: Two hundred and forty-eight patients diagnosed with MM between September 2007 and August 2024 from three large medical centers (Beijing Hospital, Peking University Cancer Hospital, and Chinese Academy of Medical Sciences Cancer Hospital) were retrospectively analyzed. Kaplan-Meier and Cox regression were performed. Breast cancer gene 1-associated protein 1 (BAP1) status was evaluated.

Results: Chinese population with MM had a lower diagnostic age, higher proportion of youth and female, more advanced stage and lower expression of characteristic markers. The median progression-free survival (mPFS) and median overall survival (mOS) were 8.90 and 25.60 months for the first-line treatment, and 3.28 and 19.50 months for the second-line. The first-line immunotherapy provided a relatively higher objective response rate (33.3% vs. 20.5%, p = 0.402) and a trend to prolong mPFS (12.10 vs. 9.20 months, p = 0.345) and mOS (NA vs. 23.90, p = 0.185) compared with chemotherapy. Bevacizumab combined with chemotherapy relatively prolonged mPFS (10.47 vs. 7.93 months, p = 0.074) and mOS (31.30 vs. 23.20 months, p = 0.673) than chemotherapy alone. Carboplatin relatively improved mPFS than cisplatin (10.87 vs. 8.87 months, p = 0.185). Age and histologic type were predictors for PFS, and gender, histologic subtype, and CK5/6 were prognosis factors for OS. Briefly, 17.78% patients existed BAP1 deletions and correlated with OS benefit.

Conclusion: Chinese population with MM present unique clinicopathologic characteristics and could benefit from the first-line immunotherapy and bevacizumab combined with chemotherapy. Gender, histologic subtype, and CK5/6 are prognosis factors for OS. BAP1 deletions correlate with OS benefit.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Clinical Significance of Bone Metastases in Pleural Mesothelioma. M. Miyake, K. Kuribayashi, H. Doi, et al. 2025;16(5):e70033. PubMed · Publisher · Free full text

Abstract

Background: Bone metastasis (BoM) is common in advanced cancer, but its incidence in pleural mesothelioma (PM) remains unclear. This study aimed to determine the incidence of BoM in PM patients and assess its prognosis and risk factors to clarify its clinical significance.

Methods: A retrospective analysis was conducted on 515 histologically confirmed PM patients enrolled between January 2011 and December 2020. The cumulative incidence of BoM was calculated using the Kaplan-Meier method, with group differences assessed via log-rank tests. Risk factors for BoM were evaluated using multivariate logistic regression.

Results: The median follow-up was 13.3 months (range: 0.2-106.7 months). BoM was detected in 59 patients (11.5%) at diagnosis or during disease progression. Multivariate analysis identified non-epithelial histology (odds ratio [OR]: 2.189, 95% confidence interval [CI]: 1.179-4.065, p = 0.013) as an independent risk factor for developing BoM. Patients with BoM had worse overall survival (OS) compared to those without BoM (median OS: 18.6 months vs. 21.7 months, p = 0.03).

Conclusions: BoM in PM occurs less frequently than in primary lung cancer, with non-epithelial histology being more commonly associated with BoM. Patients with BoM had a poor prognosis, particularly when BoM was present at diagnosis. This study is limited by its retrospective design, which may introduce biases related to data collection and patient selection. Future prospective studies are needed to validate these findings.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Cytoplasmic HuR Expression Enhances Chemoresistance in Pleural Mesothelioma Through Increased Expression of CALB2, Promotion of the E2F Pathway, and Suppression of the p53 Pathway. S. Kirimura, M. Kurata, H. Ishibashi, et al. 2025;16(7):e70062. PubMed · Publisher · Free full text

Abstract

Introduction: Chemotherapy is crucial for treating pleural mesothelioma; however, the outcomes are poor, necessitating an urgent need to study the mechanism of chemotherapy resistance in mesothelioma cells. Human antigen R (HuR), an RNA-binding protein and key post-transcriptional regulator of mRNA, is linked to poor prognosis in cancers like mesothelioma. We investigated the involvement of cytoplasmic HuR expression in drug resistance mechanisms in mesothelioma.

Methods: We retrospectively evaluated cytoplasmic HuR expression in 30 patients with pleural mesothelioma who underwent surgical resection using immunohistochemistry. We also examined the role of forced cytoplasmic expression of HuR in drug resistance using mesothelioma cell lines and performed RNA-Seq analysis to identify gene expression changes responsible for drug resistance acquisition via HuR cytoplasmic expression.

Results: Patients with mesotheliomas who expressed cytoplasmic HuR exhibited significantly worse disease-free survival following post-operative chemotherapy. Forced cytoplasmic HuR expression in mesothelioma cell lines increased chemotherapy resistance through increased expression of CALB2, upregulation of the E2F pathway and suppression of the p53 pathway.

Conclusions: Cytoplasmic HuR expression increases the chemoresistance and postoperative recurrence risk of pleural mesothelioma, making it a potential biomarker for predicting therapeutic prognosis. However, the mechanism of HuR transfer to the cytoplasm remains unclear for therapeutic application.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Epithelial-Mesenchymal Plasticity in the D-Meso-Sonobe Mesothelioma Cell Line: A Putative Model of Epithelial-Mesenchymal Transition in Mesothelioma. H. Okubo, Y. Hanamatsu, C. Saigo, et al. 2025;16(10):e70091. PubMed · Publisher · Free full text

Abstract

Epithelial-mesenchymal transition (EMT) plays a crucial role in carcinogenesis, including mesothelioma. D-Meso-Sonobe is a deciduoid-type mesothelioma cell line with morphological features similar to those of epithelioid cells. Here, we report that D-Meso-Sonobe cells exhibit spindle cell mesenchymal features under continuous confluent culture conditions. The spindle cell mesenchymal D-Meso-Sonobe expresses zinc finger E-box-binding homeobox 1 (Zeb1), which is a master regulator of EMT in the nucleus. Xenoplanted D-Meso-Sonobe cells expressed nuclear Zeb1 and yes-associated protein at the cancer invasion front and focally expressed integrin subunit alpha V and actin alpha 2, which are molecular phenotypes acquired by EMT in mesothelioma. Subsequent RNA sequencing revealed that lysyl oxidase like 1 (LOXL1) was more highly expressed in cultured spindle mesenchymal D-Meso-Sonobe cells than in epithelioid cells. LOXL1 immunoreactivity was observed at the invasive front of xenoplanted D-Meso-Sonobe cells. The epithelial-mesenchymal plasticity of D-Meso-Sonobe cells may be applicable for the development of candidate molecular agents targeting EMT in mesothelioma.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Impact of Neoadjuvant and Adjuvant Pleural Intensity-Modulated Radiotherapy in Multimodality Treatment for Malignant Pleural Mesothelioma. B. Mosleh, S. Schwarz, A. Cho, et al. 2025;16(5):e70024. PubMed · Publisher · Free full text

Abstract

Background: Few malignancies provoke as many controversies about treatment as pleural mesothelioma. There is limited experience with novel radiotherapy techniques worldwide in adjuvant and particularly in neoadjuvant settings within multimodality treatment. The objective of the current study was to investigate the long-term outcome of neoadjuvant and adjuvant pleural intensity-modulated radiotherapy (IMRT) combined with macroscopic complete resection with or without chemotherapy.

Methods: We retrospectively analyzed a consecutive cohort of 59 patients who were diagnosed with pleural mesothelioma and underwent multimodality treatment including macroscopic complete resection and neoadjuvant or adjuvant IMRT between 2005 and 2019 at the Department of Thoracic Surgery, Medical University of Vienna, Austria.

Results: In total, 59 patients (median age 59 years; IQR 54-66, male, n = 48; 81%) were included. Forty-seven patients underwent trimodality treatment consisting of induction chemotherapy, extrapleural pneumonectomy, and adjuvant IMRT. Novel neoadjuvant IMRT with (n = 9) or without (n = 3) chemotherapy followed by extrapleural pneumonectomy was performed in 12 patients. Median overall survival (OS) of all patients was 23.2 months (95% CI; 18.1-28.2) and 3- and 5-year survival rates were 33% and 28%, respectively. Survival was comparable between therapies including neoadjuvant versus adjuvant IMRT (median OS 17.5 vs. 24.0 months, p = 0.39).

Conclusions: Neoadjuvant pleural IMRT has been investigated as a novel treatment option for highly selected cases in pleural mesothelioma. Neoadjuvant IMRT was effective and safe in patients treated in a high-volume institution but showed no relevant survival benefit compared to adjuvant IMRT within multimodality treatment.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Circulating SMRP and CA-125 before and after pleurectomy decortication for pleural mesothelioma. J. Paajanen, A. Sadek, W.G. Richards, et al. 2024;15(15):1237-1245. PubMed · Publisher · Free full text

Abstract

Background: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin-related protein (SMRP) and cancer antigen 125 (CA-125) are established blood-based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD).

Methods: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post-operation, and (3) recurrence.

Results: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow-up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA-125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease-free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA-125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA-125 across the study timepoints (p = 0.47).

Conclusions: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA-125 could be helpful in recognizing abdominal recurrences.

© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Comparative efficacy of immune checkpoint inhibitors versus chemotherapy alone in diffuse pleural mesothelioma. X. Zhang, L. Chang, Q. Ma, et al. 2024;15(20):1590-1597. PubMed · Publisher · Free full text

Abstract

Background: This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real-world diffuse pleural mesothelioma patients in China.

Methods: Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs-treated group (n = 46) and the chemotherapy-only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored.

Results: The median progression-free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs-treated group and the chemotherapy group, respectively. The ICIs-treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan-Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38-0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26-0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend.

Conclusion: In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first- and second-/third-line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival. M. Nie, Z. Sun, N. Li, et al. 2024;15(19):1502-1512. PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM.

Methods: DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023.

Results: Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (<6.637), lower evenness (<0.028), or higher clonality (≥0.194) according to baseline tumor tissue TCR indexes, demonstrated poorer OS. Furthermore, patients with TP53, CDKN2A, or CDKN2B variants and those with a lower evenness (<0.030) in baseline tumor tissue showed worse immunotherapy efficacy. The present study is the first to identify five special TCR Vβ-Jβ rearrangements associated with MM immunotherapy efficacy.

Conclusions: The present study reported the largest-scale genomic landscape and TCR repertoire of MM in Chinese patients and identified genomic and TCR biomarkers for the prognosis and immunotherapy efficacy in MM. The study results might provide new insights for prospective MM trials using specific genes, TCR indexes, and TCR clones as biomarkers and offer a reference for future antitumor drugs based on TCR-specific clones.

© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies. H. Kozai, H. Ogino, A. Mitsuhashi, et al. 2024;15(5):369-378. PubMed · Publisher · Free full text

Abstract

Background: Immune checkpoint inhibitors (ICIs) are a revolutionary paradigm in the treatment of thoracic malignancies and chemoimmunotherapy is a current standard care in this field. Chemotherapeutic agents are known to induce not only direct cytotoxic effects on tumor cells but also immune modulating effects, such as stimulating immunogenic cell death (ICD). Currently, either pemetrexed (PEM) or taxane plus platinum are combined with ICIs for patients with non-small cell lung cancer (NSCLC); however, it is still unknown whether these agents are immunologically optimal partners for ICIs.

Methods: To determine the immunologically optimal chemotherapeutic agent, we first evaluated the ability of several chemotherapeutic agents, including platinum, PEM, taxane, and 5-fluorouracil (5-FU) to induce ICD using several thoracic tumor cell lines in vitro. ICD was evaluated by the cell surface expression of calreticulin (CRT) and adenosine-triphosphate (ATP) secretion. We further performed an antitumor vaccination assay in vivo.

Results: 5-FU induced cell surface expression of CRT and ATP secretion most efficiently among the several chemotherapeutic agents. This effect was enhanced when it was combined with platinum. In the antitumor vaccination assay in vivo, we found that vaccination with dying-AB1-HA (a murine malignant mesothelioma cell line) cells treated with 5-FU, but neither PEM nor PTX, reduced the tumor growth of living-AB1-HA cells inoculated 1 week after vaccination by recruiting CD3+ CD8+ T cells into the tumor microenvironment.

Conclusion: Our findings indicate that fluoropyrimidine can be an immunologically optimal partner of ICIs through the induction of ICD for thoracic malignancies.

© 2023 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.
Chinese expert consensus on the diagnosis and treatment of malignant pleural mesothelioma. Q. Wang, C. Xu, W. Wang, et al. 2023;14(26):2715-2731. Consensus statement PubMed · Publisher · Free full text

Abstract

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

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis. B. Mosleh, K. Schelch, T. Mohr, et al. 2023;14(22):2177-2186. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker.

Methods: FGF18 mRNA expression was analyzed by real-time PCR in cell lines and in silico in datasets from the Cancer Genome Atlas (TCGA). Cell lines overexpressing FGF18 were generated by retroviral transduction and cell behavior was investigated by clonogenic growth and transwell assays. Plasma was collected from 40 PM patients, six patients with pleural fibrosis, and 40 healthy controls. Circulating FGF18 was measured by ELISA and correlated to clinicopathological parameters.

Results: FGF18 showed high mRNA expression in PM and PM-derived cell lines. PM patients with high FGF18 mRNA expression showed a trend toward longer overall survival (OS) in the TCGA dataset. In PM cells with low endogenous FGF18 expression, forced overexpression of FGF18 resulted in reduced growth but increased migration. Surprisingly, despite the high FGF18 mRNA levels observed in PM, circulating FGF18 protein was significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. No significant association of circulating FGF18 with OS or other disease parameters of PM patients was observed.

Conclusions: FGF18 is not a prognostic biomarker in PM. Its role in PM tumor biology and the clinical significance of decreased plasma FGF18 in PM patients warrant further investigation.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Diagnosis of malignant pleural disease: Ultrasound as "a detective probe". G. Messina, M. Bove, G. Natale, et al. 2023;14(3):223-230. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is an invasive, aggressive pleural tumor with a predominantly local spread. The objective of this study was to assess thoracic ultrasound (TUS) as an imaging modality with high sensitivity for the identification of malignant pleural involvement and in order to guide pleural biopsies.

Methods: In this retrospective single-center study between January 2018 and June 2022, 51 consecutive patients with impassable circumferential pleural thickening underwent TUS at the Thoracic Surgery Unit of the Vanvitelli University of Naples. Pleural biopsies were performed, and then large and multiple samples were sent to the pathological anatomy for histological examination.

Results: In all patients who underwent ultrasound examination, we chose the optimal point of entry to perform pleural biopsies and selected the areas of greater thickening without pleural effusion. No patient had any complications. No drainage tubes were placed after the pleural biopsies and no pneumothorax was present during the following days of hospitalization. The patients were discharged on the second postoperative day.

Conclusion: With TUS the precise pleural thickening localization, local infiltration, mass extent, its nature (solid, cystic or complex) and ultrasound features can be easily defined. Furthermore, ultrasound is more economical than computed tomography and avoids the risks associated with radiation. Thoracic ultrasound is an important component of the diagnostic procedure in detecting a safe entry site for biopsies of MPMs.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
En bloc resection of the recurrent pleural mesothelioma and reconstruction of the chest wall after immunotherapy: A case report. C. Qin, Q. Xia, Z.J. Chen, et al. 2023;14(30):3063-3066. Case report PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is associated with previous asbestos exposure, while more clinical insights into this disease have come from other case studies. Maximal cytoreduction is critical in disease control and might help to improve the prognosis. Here, a 41-year-old female presented with a 6-month history of a mass detected in the chest wall following resection of a right pleural mesothelioma 2 years previously. A fluorodeoxyglucose positron emission tomography/computed tomography scan showed a right chest wall mass with a blurred boundary 8.9 cm × 3.7 cm in size. The patient had received one cycle of bevacizumab, carboplatin, and pemetrexed, and two cycles of nivolumab, ipilimumab, and gemcitabine 5 months before admission. We subsequently resected the tumor, the involved diaphragm, and the fifth and sixth ribs, and titanium mesh and continuous suture were used to close the thoracic cage. The fixed paraffin-embedded tissues showed epithelioid pleural mesothelioma. The patient received nivolumab and ipilimumab postoperatively, and no recurrence was detected 16 months after surgery. En bloc resection with reconstructive surgery effectively removed the locally advanced malignancy and restored the biological function of the thorax with a favorable prognosis. Neoadjuvant immunotherapy might therefore be conducive to radical resection and perioperative immunotherapy might improve the prognosis.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma. Y. Yin, R. Sakakibara, T. Honda, et al. 2023;14(20):1991-2000. PubMed · Publisher · Free full text

Abstract

Background: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer.

Methods: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence.

Results: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group.

Conclusions: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Highlighting the immunohistochemical differences of malignant mesothelioma subtypes via case presentations. A. Sejben, T. Pancsa, L. Tiszlavicz, et al. 2023;14(10):857-863. Review PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare tumor of mesothelial cells, with an increasing incidence both in developed and developing countries. MM has three major histological subtypes, in order of frequency, according to the World Health Organization (WHO) Classification of 2021: epithelioid, biphasic, and sarcomatoid MM. Distinction may be a challenging task for the pathologist, due to the unspecific morphology. Here, we present two cases of diffuse MM subtypes to emphasize the immunohistochemical (IHC) differences, and to facilitate diagnostic difficulties. In our first case of epithelioid mesothelioma, the neoplastic cells showed cytokeratin 5/6 (CK5/6), calretinin, and Wilms-tumor-1 (WT1) expression, while remaining negative with thyroid transcription factor-1 (TTF-1). BRCA1 associated protein-1 (BAP1) negativity was seen in the neoplastic cells' nucleus, reflecting loss of the tumor suppressor gene. In the second case of biphasic mesothelioma, expression of epithelial membrane antigen (EMA), CKAE1/AE3, and mesothelin was observed, while WT1, BerEP4, CD141, TTF1, p63, CD31, calretinin, and BAP1 expressions were not detected. Due to the absence of specific histological features, the differentiation between MM subtypes could be a challenging task. In routine diagnostic work, IHC may be the proper method in distinction. According to our results and literature data, CK5/6, mesothelin, calretinin, and Ki-67 should be applied in subclassification.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Immune-related adverse events in hepatitis treated with thiopurine-based immunosuppressants: A case report. K. Kawakado, K. Nakashima, H. Tobita, et al. 2023;14(13):1208-1211. Case report PubMed · Publisher · Free full text

Abstract

An 82-year-old man was treated with ipilimumab and nivolumab for malignant pleural mesothelioma. Although he was previously treated with prednisolone (1 mg/kg/day) for immune-related adverse event (irAE) hepatitis by a previous doctor, he still had worsening liver function and was transferred to our hospital. Blood tests and imaging findings were negative for autoimmune and infectious hepatitis, and liver biopsy results were consistent with irAE hepatitis. Steroid pulse therapy improved liver function, but tapering to prednisolone (1 mg/kg/day) again worsened his liver function. Concomitant use of mycophenolate mofetil was initiated, but no improvement in liver function was observed, therefore azathioprine, a thiopurine immunosuppressant, was administered in combination with steroids. During the course of treatment, hepatic dysfunction due to azathioprine was suspected, and the concomitant use of mercaptopurine and prednisolone was started. Afterward, the liver function improved, and the prednisolone dose was gradually reduced to 10 mg/day. This is a rare case in which a thiopurine-based immunosuppressant was effective against irAE hepatitis, therefore thiopurine-based immunosuppressants may be effective against steroid-refractory hepatitis.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Strategies to reduce morbidity following pleurectomy and decortication for malignant pleural mesothelioma. P. Bou-Samra, A. Chang, K. Zhang, et al. 2023;14(27):2770-2776. PubMed · Publisher · Free full text

Abstract

Background: Pleurectomy and decortication (PD) in malignant pleural mesothelioma has a high morbidity mostly associated with aspiration pneumonia (PNA), deep vein thrombosis (DVT), and foreign catheter sepsis. We instituted four strategies to reduce these complications and report our experience.

Methods: This was a retrospective review of patients who underwent PD at the University of Pennsylvania between 2015 and 2022. Our patients underwent standard of care PD in addition to tracheostomy and gastrostomy/jejunostomy tube with therapeutic anticoagulation (AC) leading up to surgery. Measured outcomes were postoperative PNA, DVT, and sepsis. The predicted risk of those same outcomes had patients not undergone the interventions was calculated based on the American College of Surgeons (ACS) surgical risk calculator (SRC). A McNemar's test was used to determine whether the risk of having PNA, DVT and sepsis differed between the two subgroups.

Results: Fifty-five patients were included in the study. The mean age was 70 years (SD 6.2) with a mean of 21 (SD 19) pack-years of smoking. PNA, DVT, and catheter-related sepsis occurred in 12, four, and seven patients, respectively. Upon using the ACS SRC prediction model of the nonintervention group, PNA, DVT and catheter related sepsis was predicted to occur in 24 (paired data OR 5, 95% CI: 1.4-17.2; McNemar's test p = 0.008), 14 (paired data OR 3.5, 95% CI: 1.15-10.6; McNemar's test p = 0.03), and 17 (paired OR 3, 95% CI: 1.09-8.3; McNemar's test p = 0.04) patients, respectively.

Discussion: Patients undergoing tracheostomy creation, therapeutic AC at the time of diagnosis, and gastrostomy tube placement had a reduced risk of aspiration PNA, DVT, and catheter sepsis.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Unprecedented long-term survival in a patient with malignant pleural mesothelioma treated with subsequent systemic chemo- and immunotherapeutic regimens. L. Cerbone, S. Delfanti, A.M. De Angelis, et al. 2023;14(5):524-527. Case report PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is a rare disease with a dismal prognosis and few therapeutic options. Until recently the median overall survival for a pleural mesothelioma patient was up to 2 years, with few exceptional cases of patients achieving a longer survival. Here, we report the clinical case of a patient whose survival spanned over 10 years. The patient underwent several systemic treatments, including three different chemotherapy lines (cisplatin-pemetrexed, vinorelbine and platinum rechallenge) and two immunotherapy regimens using immune checkpoint inhibitors (anti CTLA-4 tremelimumab and anti PD-1 nivolumab). At the time this report was written, the patient was off-treatment, asymptomatic and with a stable radiological disease. Our case demonstrates that a prolonged survival with a preserved quality of life may be reached in selected patients through the exploitation of the available treatments in an expertise setting.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Whole-exome sequencing in primary pulmonary synovial sarcoma misdiagnosed as mesothelioma: A case report and literature review. D. Wu, H. Zhang, X. Li, et al. 2023;14(16):1520-1529. Review · Case report PubMed · Publisher · Free full text

Abstract

Synovial sarcoma is a highly malignant tumor that accounts for 10% of all soft tissue sarcomas. Primary pulmonary synovial sarcoma (PPSS) is extremely rare, and its prognosis is poor. A diagnosis is usually established after other primary lung malignancies or metastatic extrathoracic sarcomas have been excluded. Therefore, it is often misdiagnosed. In this study, we report the case of a 38-year-old woman who was misdiagnosed as having pleural mesothelioma and finally endured surgery to remove the tumor. The tumor showed SYT-SSX fusion transcripts and was diagnosed as PPSS after combining histopathological and immunohistochemical analyses. Finally, we determined some biomarkers through whole-exome sequencing (WES) to improve the diagnosis and treatment strategies.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
A comprehensive study of alternative splicing in malignant pleural mesothelioma identifies potential therapeutic targets in a new cluster with poor survival. M.M. Shao, X. Qiao, Q.Y. Chen, et al. 2022;13(16):2318-2330. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is one of the most aggressive tumors with few effective treatments worldwide. It has been suggested that alternative splicing at the transcriptome level plays an indispensable role in MPM.

Methods: We analyzed the splicing profile of 84 MPM patients from the TCGA cohort by using seven typical splicing types. We classified MPM patients based on their splicing status and conducted a comprehensive analysis of the correlation between the splicing classification and clinical characteristics, genetic variation, pathway changes, immune heterogeneity, and potential therapeutic targets.

Results: The expression of the alternative splicing regulator SRPK1 is significantly higher in MPM tissues than in normal tissues, and correlates with poor survival. SRPK1 deficiency promotes MPM cell apoptosis and inhibits cell migration in vitro. We divided the MPM patients into four clusters based on their splicing profile and identified two clusters associated with the shortest (cluster 3) and longest (cluster 4) survival time. We present the different gene signatures of each cluster that are related to survival and splicing. Comprehensive analysis of data from the GDSC and TCGA databases revealed that cluster 3 MPM patients could respond well to the small-molecule inhibitor CHIR-99021, a small-molecule inhibitor of GSK-3.

Conclusion: We performed unsupervised clustering of alternative splicing data from 84 MPM patients from the TCGA database and identified a cluster associated with the worst prognosis that was sensitive to a GSK-3 inhibitor.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Diagnostic pitfall in a large cell lung cancer with testicular metastasis synchronous malignant pleural mesothelioma patient: A case report. L. Jiang, V.A. De Souza, N.M. George, et al. 2022;13(15):2253-2256. Case report PubMed · Publisher · Free full text

Abstract

Large cell lung cancer metastases to the testis are scarce, although it is the most common malignancy and the most common site of metastases for breast, colorectal and kidney cancers. We hereby report a 28-year-old male patient admitted to our hospital with a chief complaint of scrotal enlargement, accompanied by chest pain and progressive dyspnea. The definite diagnosis was malignant pleural mesothelioma with the synchronous occurrence of large cell lung cancer with testicular metastasis. Sophisticated clinical manifestation of symptoms led to a time-consuming diagnosis, while the patient's condition deteriorated rapidly. Herein, we present this case to share our hard-learnt experience to increase clinician awareness and contribute to the information in the literature.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Epidemiologic evaluation of pleurisy diagnosed by surgical pleural biopsy using data from a nationwide administrative database. K. Hara, K. Yamasaki, M. Tahara, et al. 2022;13(8):1136-1142. PubMed · Publisher · Free full text

Abstract

Background: Pleural biopsies for investigating the causes of pleurisy are performed through modalities including needle biopsies, local anesthetic thoracoscopic procedures, and surgery (video-assisted thoracoscopic surgery and open thoracotomy). To date, there have been no large-scale nationwide epidemiological studies regarding pleurisy diagnosed via surgical pleural biopsy. This study examined the epidemiology of pleurisy diagnosed via surgical pleural biopsy in a Japanese nationwide administrative database.

Methods: We evaluated Japanese Diagnosis Procedure Combination data of 24 173 patients who underwent video-assisted thoracoscopic surgery or open thoracotomy and received a diagnosis of pleurisy between April 2014 and March 2020. In addition to pleurisy diagnoses, the patients' clinical information, including age, sex, smoking status (pack-years), dyspnea grade, length of in-hospital stay, and comorbidities, were extracted from the dataset.

Results: This study included data from 1699 patients. The most frequent causes of pleurisy were neoplastic diseases (55.9%; malignant mesothelioma 22.5%, lung cancer 15.7%, lymphoma 2.5%), followed by infectious diseases (24.0%; tuberculosis 16.2%, parapneumonic pleural effusion 3.6%, empyema 3.5%, nontuberculous mycobacteriosis 0.5%), collagen vascular diseases (2.8%; rheumatoid arthritis 1.3%, immunoglobulin G4-related diseases 0.7%, systemic lupus erythematosus 0.3%), and paragonimiasis (0.1%).

Conclusions: Neoplastic diseases, including malignant mesothelioma and lung cancer, were frequently and accurately diagnosed as pleurisy via surgical pleural biopsy. The next leading cause was infectious diseases such as mycobacterial infections. Physicians should consider performing surgical biopsy in light of the knowledge regarding the etiology of pleurisy when a definitive diagnosis cannot be made via needle pleural biopsy.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Feasibility and safety of extended pleurectomy/decortication for malignant pleural mesothelioma. A single group experience. F. Falanga, P. Rinaldi, C. Primiceri, et al. 2022;13(19):2792-2798. PubMed · Publisher · Free full text

Abstract

Surgery is part of a multimodal therapeutic approach to malignant pleural mesothelioma (MPM) although its real beneficial effect is still controversial. The optimal precise sequence of treatments within the trimodality is unclear, and should be decided upon a multidisciplinary consensus for each individual patient. Here, we analyzed the perioperative data of 19 MPM patients who underwent extended pleurectomy/decortication (EPD) with curative intent. The mean age at diagnosis was 67 years; 11 males and eight females. Ten patients were diagnosed with MPM via medical thoracoscopy (MT), and nine via video-assisted thoracoscopic surgery (VATS). The vast majority of cases harbored epitheliod forms. We compared neoadjuvant chemotherapy (NCT) followed by surgery (11 cases) versus surgery followed by adjuvant chemotherapy (ACT, 8 cases) within a 3-year period. All patients had extended pleurectomy/decortication and none had an extended pneumonectomy. Analysis of survival curves suggested that the short-term outcomes are better with upfront EDP followed by ACT if compared to EDP preceded by NCT. Although limited, the data highlighted the safety and feasibility of EPD, with manageable postoperative complications and no major burden for the patients.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Mixed micropapillary patterns found in malignant pleural mesothelioma with possibly worsened prognostic implication. T. Oyama, T. Goto, K. Amemiya. 2022;13(7):1098-1099. PubMed · Publisher · Free full text
Non-incisional pleurectomy/decortication for malignant mesothelioma after cardiac surgery. K. Miura, K. Shimizu, S. Hasegawa, et al. 2022;13(1):126-128. Case report PubMed · Publisher · Free full text

Abstract

A 70-year-old man diagnosed with right-sided malignant epithelial pleural mesothelioma, underwent pleurectomy/decortication after three courses of neoadjuvant chemotherapy. He had a history of mitral valve replacement and maze procedure with median sternotomy, and the procedures resulted in strong adhesion from the apex to the mediastinal side. In particular, the peeling of the area where the tumor invaded the pericardium required the most attention; however, the involved pericardium could be partially resected without damaging the right atrium. Finally, en bloc macroscopic complete resection with the entire pleura was successfully performed without conversion to extrapleural pneumonectomy.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Rapidly progressing metastatic malignant melanoma mimicking primary pleural tumor: A case report. C. So, T. Yoshida, T. Mizuno, et al. 2022;13(9):1423-1426. Case report PubMed · Publisher · Free full text

Abstract

Malignant melanoma is the most aggressive skin cancer that originates from melanocytes. Primary or metastatic pleural melanoma shares clinical and imaging characteristics with primary pleural tumors, such as pleural mesothelioma. Identification of the primary site can be challenging to distinguish between primary and secondary melanomas. We report a case of a 46-year-old woman with metastatic, rapidly progressing pleural melanoma mimicking primary pleural tumor. The metastatic pleural tumor from a primary cutaneous melanoma was diagnosed by reevaluating a previous surgical specimen. When evaluating patients with pleural melanoma, the primary site should be reevaluated to distinguish between primary and secondary melanomas.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
The impact of COVID-19 on new mesothelioma diagnoses in Italy. L. Mangone, P. Mancuso, I. Bisceglia, et al. 2022;13(5):702-707. PubMed · Publisher · Free full text

Abstract

Background: The aim of this work was to evaluate the impact of the restrictions put in place to control the COVID-19 pandemic on new diagnoses of malignant mesothelioma (MM) in Italy.

Methods: Twelve of the 21 Italian malignant mesothelioma CORs (regional operating centres) participated. The study included all cases of MM with microscopic confirmation; cases without microscopic confirmation and death certificate only (DCO) were excluded. For each case, information on sex, date of birth, tumor site, morphology, and date of diagnosis was retrieved. We compared the number of incident cases in 2020 with 2019, looking at the overall picture and for four periods: pre-pandemic (January-February), first wave (March-May), low incidence (June-September), and second wave (October-December).

Results: A total of 604 cases were registered: 307 in 2019 and 297 in 2020. In the 2020 pre-pandemic period, the incidence was higher than in the same months in 2019 (+45%); there was no significant change during the first wave (+1%) or in the low-incidence period (-3%), while a decrease was observed during the second wave (-32%). However, the data were not homogeneous across the country: the increase in the pre-pandemic period concerned mostly the regions of northern (+61.5%) and central Italy (+43.5%); during the first wave, MM diagnoses increased in the northern (+38.5%) and central (+11.4%) regions but decreased in the southern regions (-52.9%). All these differences are compatible with random fluctuations.

Conclusion: The COVID-19 pandemic had little or no impact on new MM diagnoses, and variations were not homogeneous throughout the country.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Tumor suppressor effect of an antibody on xenotransplanted sarcomatoid mesothelioma cells. M. Hasegawa, Y. Hanamatsu, C. Saigo, et al. 2022;13(18):2566-2573. PubMed · Publisher · Free full text

Abstract

Background: As mesothelioma generally has an unfavorable prognosis, further advances are needed to improve the outcomes in patients with mesothelioma. In the present study, we generated and characterized a monoclonal antibody that could inhibit mesothelioma cell proliferation in a xenotransplantation mouse model.

Methods: We generated monoclonal antibodies by immunizing mice with cultured mesothelioma cells. These antibodies were then characterized by immunofluorescence staining, immunohistochemical staining, secondary antibody-drug conjugate assay, antibody inoculation in a xenotransplantation mesothelioma mouse model, and mass spectrometry followed by small interfering RNA (siRNA) analysis. 5' rapid amplification of complementary DNA ends followed by sequencing was performed to deduce the amino acid sequences of the variable regions of the light and heavy chains of AX10.

Results: An IgG2b κ-type AX10 antibody against the cell surface membrane of sarcomatoid mesothelioma cells was generated. AX10 immunoreactivity was detected in 12 out of 22 different mesothelioma tissue specimens, but there was little AX10 immunoreactivity in a normal human tissue array. AX10 decreased Matrigel invasion by MPM-1 cells but did not affect cell proliferation. Notably, AX10 significantly inhibited the proliferation of MPM-1 cells xenotransplanted into Severe combined immunodeficiency-Nonobese diabetic mice. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry followed by siRNA silencing indicated that AX10 reacted to a unique alternatively spliced isoform of sarcolemma-associated protein. AX10 is composed of as yet unregistered amino acid sequences in its variable region.

Conclusions: AX10 could have therapeutic potential for patients with sarcomatoid mesothelioma.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Diagnostic value of microRNAs for malignant pleural mesothelioma: A mini-review. Y.Q. Han, S.C. Xu, W.Q. Zheng, et al. 2021;12(1):8-12. Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a type of cancer originating from the pleura with high aggressiveness and poor prognosis. A timely diagnosis is crucial to improve its prognosis. Laboratory biomarkers have significant advantages of reduced invasiveness, low cost, and are observer-independent, and therefore represent a promising diagnostic tool for MPM. MicroRNA is a family of non-coding RNA that regulates gene expression at the post-transcriptional level. Accumulated studies showed that microRNA, either in tissue, circulating, and body fluid, has potential diagnostic value for various disorders. Here, we reviewed the diagnostic value of microRNA for MPM.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Does the LENT score risk-stratify patients with malignant pleural mesothelioma? An observational study. B. Chollet, J. Guinde, S. Laroumagne, et al. 2021;12(11):1752-1756. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare, highly aggressive and deadly disease with a poor patient life expectancy. A few years ago, the main challenge was the histological diagnosis of this disease; at present, the search for the best therapeutic strategy is now a priority. However, an optimal therapeutic strategy is not yet clear, despite growing efforts in the treatment armamentarium and research, and at the era of tailored and individualized treatment, tools to predict patient survival are needed for therapeutic decision-making. Among them, the LENT scoring system was developed to predict prognosis in patients with malignant pleural effusion. The aim of this study was to assess the performance of the LENT score in predicting prognosis in patients with MPM.

Methods: A retrospective observational study was conducted by analyzing the prospective collected databases of patients undergoing medical thoracoscopy in a single center with a final diagnosis of MPM confirmed by the MESOPATH National Reference Center.

Results: A total of 41 patients with MPM were studied. All patients underwent platinum-based chemotherapy combined with pemetrexed ± bevacizumab. No high-risk category patients were found using the LENT scoring system in this cohort. The median (range) LENT score at the time of medical thoracoscopy was 0 (0-3) and the median survival was 15.5 (2-54) months for the entire cohort. The median survival of low-risk and moderate-risk category patients was 21.4 months (2-54, 32 patients) and 6.7 months (2-19, nine patients), respectively. A total of 27 patients with MPM of epithelial subgroup had a median LENT score of 1 (0-2) with a 26 (2-54) months median survival. The median LENT score and median survival of nonepithelial mesothelioma patients (biphasic MPM subgroup, eight patients; sarcomatoid MPM subgroup, six patients) were 0 (0-3) and 11 (2-52) months, respectively.

Conclusions: Applied to a homogenous cohort of MPM patients, the LENT score underestimated prognosis and was not useful per se for the management of this disease, as evidenced in the epithelial mesothelioma subgroup of patients in our study.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Evidence for marked underutilization of insurance billing in malignant pleural mesothelioma in Finland. P. Torkki, J. Paajanen, V. Kytö, et al. 2021;12(19):2594-2600. PubMed · Publisher · Free full text

Abstract

Background: Substantial variation in health care costs for malignant pleural mesothelioma (MPM) has previously been identified.

Materials And Methods: We analyzed the changes in health care costs in MPM in Finland during 2002-2012. Finland has low-threshold public health care and a mandatory Workers' Compensation scheme that covers all occupational-related disease expenses. The costs include treatment costs for inpatients, hospice care, medication costs, rehabilitation costs, and travel costs. All costs are expressed in 2012 prices, adjusted using the consumer price index.

Results: A total of 907 MPM patients were included in the study. Mean duration of inpatient episodes increased 7% per year from 2002 to 2012, correlating with total costs (R2 = 0.861, p < 0.05). The annual total costs for treatment increased from 1.7 to 4.3 m€ during the study period and the cost per patient from 27 000 to 43 000 €. The overall costs increased progressively by the number of procedures performed. In patients who had been compensated for occupational cause by Workers' Compensation Center, only 36% of the overall care costs were billed from the insurance company. Billing of inpatient costs was 86% in these patients.

Conclusion: During the study period, we found that the costs of MPM increased more than the average health care costs. This may be because of advanced diagnostic workup or more costly treatment (e.g., pemetrexed). Moreover, only one-third of all health care costs are charged to Workers' Compensation Insurance.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Functional inhibition of heat shock protein 70 by VER-155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism. K. Sakai, M. Inoue, S. Mikami, et al. 2021;12(4):491-503. PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma, a devastating asbestos-associated malignancy, urgently requires a novel effective therapy. Heat shock protein 70 (HSP70), which is synthesized in the cell response to protein damage, is expected to be a new target for antitumor treatment. In addition to its well-known protein refolding function, HSP70 regulates cell proliferation through different pathways, including PI3K/AKT/mTOR, and autophagy in malignant cells. In this study, we attempted to clarify the effects of VER-155008, an HSP70 inhibitor, on pleural mesothelioma.

Methods: Human pleural mesothelioma cell lines 211H, H2452 and H28 were cultured with VER-155008, and protein expression, cell proliferation, colony formation, cell cycle, synergistic effect with cisplatin, and autophagy induction were analyzed.

Results: In mesothelioma cell lines, VER-155008 (5.0 μM or more) inhibited cell growth and colony formation, accompanied by G1 cell cycle arrest. According to western blot analysis, VER-155008 reduced p-AKT expression. However, VER-155008 failed to show a synergistic effect with cisplatin on cell growth. Mesothelioma cells transfected with the novel plasmid pMRX-IP-GFP-LC3-RFP-LC3ΔG, which was developed for the quantitative and statistical estimation of macroautophagy, showed enhanced macroautophagy upon treatment with VER-155008 and gefitinib which is an EGFR-tyrosine kinase inhibitor. In addition, fetal bovine serum deprivation induced macroautophagy was further enhanced by VER-155008.

Conclusions: On the basis of these results, functional HSP70 inhibition by VER-155008 suppressed cell growth in pleural mesothelioma cells, accompanied by enhanced macroautophagy. HSP70 inhibition is thus expected to become a new strategy for treating mesothelioma.

Key Points: Significant findings of the study In pleural mesothelioma cells, inhibition of HSP70 function by VER-155008 suppressed cell proliferation accompanied by induction of autophagy which was synergistically enhanced under the starvation condition, whereas gefitinib, an EGFR-TKI, did not show the same synergistic effect in autophagy. What this study adds The inhibition of HSP70 induced autophagy and suppressed cell proliferation in mesothelioma cells.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Malignant pleural mesothelioma in a kidney transplant recipient. W. Traipipitsiriwat, C. Songsomboon, D. Junhasavasdikul, et al. 2021;12(8):1260-1263. Case report PubMed · Publisher · Free full text

Abstract

Post-transplantation malignancy is one of the most common complication-related mortality in transplant recipients. Here, we report the case of a kidney transplant patient for 2 years with malignant pleural effusion that was subsequently diagnosed as malignant pleural mesothelioma.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Malignant pleural mesothelioma in a patient with pneumothorax: A cumbersome subtype both clinically and pathologically. T. Fukui, T. Okubo, N. Tanimoto, et al. 2021;12(6):974-977. Case report PubMed · Publisher · Free full text

Abstract

Here, we report a case of malignant pleural mesothelioma (MPM) that was very difficult to diagnose. A 62-year-old woman with a surgical history of recurrent bilateral pneumothorax was admitted to our hospital with severe dysphagia. Computed tomography (CT) detected stenosis in the lower esophagus. Immunohistochemical examination of a biopsy sample from the stenotic region was suggestive of MPM. Chemotherapy was initiated, but the patient soon weakened and died. Autopsy revealed atypical cells, identical to those seen in the biopsy sample which had spread into the stenotic esophagus and entire thoracic cavity. Although neither pleural thickening/nodules nor asbestos bodies were observed, we finally diagnosed the tumor as a biphasic-type MPM. We re-examined previous surgical specimens of pneumothorax and acknowledged foci of bland mesothelial cell proliferation which had the same pathological findings as tumor cells at autopsy. The lack of asbestos exposure and pleural thickening, an initial manifestation of pneumothorax, and faint cytological atypia prevented an early diagnosis. In cases of recurrent pneumothorax in elderly patients, MPM should be included in the differential diagnosis.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Mediastinal undifferentiated pleomorphic sarcoma with pleural effusion cytopathologically misdiagnosed as epithelial malignant pleural mesothelioma: An autopsy case report. K. Matsumoto, Y. Nakamura, Y. Inagaki, et al. 2021;12(7):1137-1140. Case report PubMed · Publisher · Free full text

Abstract

Undifferentiated pleomorphic sarcoma (UPS) is a new disease in the World Health Organization's classification of tumors of soft tissue and bone published in 2013. Primary mediastinal UPS is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, which was initially misdiagnosed as epithelial malignant pleural mesothelioma (MPM). The cytopathological findings of the pleural effusion cell block often contribute to the diagnosis of various malignant tumors. However, these findings may lead to misdiagnosis of highly invasive mediastinal tumors such as UPS. A biopsy for primary mediastinal lesions should be performed because MPM rarely mimics mediastinal tumors with pleural effusion.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Pleural mesothelioma: When echo-endoscopy (EUS-B-FNA) leads to diagnosis in a minimally invasive way. R. Piro, M. Fontana, F. Livrieri, et al. 2021;12(6):981-984. Case report PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an asbestos-related and locally invasive tumor with poor prognosis. The acquisition of histological material is mandatory in order to establish a diagnosis. In this situation, the sampling of tissue is generally performed via a thoracoscopic pleural biopsy, either medically or surgically. The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or transesophageal fine needle aspiration with an EBUS scope (EUS-B-FNA) of pleural lesions have only rarely been reported due to the theoretical limitations of tissue acquisition in such cases. We herein report a rare case of MPM successfully diagnosed via EUS-B-FNA in a 49-year-old woman with an unusual presentation characterized by solid thickening in the right mediastinal pleura.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Prediction modeling using routine clinical parameters to stratify survival in malignant pleural mesothelioma patients complicated with malignant pleural effusion. S. Zhang, Y. Zhang, W. Feng, et al. 2021;12(24):3304-3309. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural effusion (MPE) is common in malignant pleural mesothelioma (MPM). The survival of patients with MPM and MPE is heterogeneous. The LENT and BRIMS scores using routine clinical parameters were developed to predict the survival of patients with unselected MPE and MPM, respectively. This study aimed to stratify the survival of selected MPM patients with MPE.

Methods: Data were collected from subjects diagnosed with MPM and MPE. The LENT and BRIMS scores were applied using a combination of clinical variables to stratify subjects and compare survival characteristics.

Results: In total, 101 patients with MPM complicated by MPE were included in the study. The median follow-up time was 71 months (interquartile range: 24-121 months). Overall median survival was 24 (interquartile range: 12-52 months). Based on the LENT score, the low-, moderate-, and high-risk groups accounted for 65.3% (66 cases), 34.7% (35 cases), and 0%, respectively. The cumulative survival rates of the two groups were statistically significant (p = 0.031). The area under the curve (AUC) of the LENT score was 0.662. Based on the BRIMS score, the first, second, third, and fourth risk groups accounted for 1.0% (1 case), 42.9% (35 cases), 28.7% (29 cases), and 19.4% (36 cases), respectively. Survival was significantly higher in patients in the risk groups 1 and 2 than in patients in the risk groups 3 and 4 (p = 0.037). The AUC of the BRIMS score was 0.605.

Conclusions: Using routinely available clinical variables, both LENT and BRIMS scores could stratify selected MPM and MPE patients into risk groups with statistically different survival.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Premature phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma. K. Watanabe, Y. Okuma, S. Kawai, et al. 2021;12(11):1668-1672. PubMed · Publisher · Free full text

Abstract

Background: Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next-generation anthracycline that is commonly used to treat lung cancer. Here, we conducted a phase II trial of this drug in patients with previously treated MPM.

Methods: Eligible patients with MPM having adequate organ function and a performance status of 0-2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1-3 every three weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Median progression-free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events were evaluated as secondary endpoints.

Results: This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2-11.2) months, and the median OS was 9.1 (range, 6.2-22.0) months. The median number of treatment cycles was three (range, 2-11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia.

Conclusions: Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma. J. Guzmán-Casta, S. Carrasco-CaraChards, J. Guzmán-Huesca, et al. 2021;12(7):1014-1022. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years.

Methods: This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression-free survival (PFS).

Results: A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4-9.5 months) and median OS was 12 months (95% CI: 11.3-12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment.

Conclusions: Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Pseudomesotheliomatous carcinoma of lung adenocarcinoma diagnosed using transesophageal ultrasound-guided bronchoscopic aspiration. T. Sumi, H. Nakata, Y. Mori, et al. 2021;12(9):1465-1466. Case report PubMed · Publisher · Free full text

Abstract

Endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA), a minimally invasive procedure, may be useful for the diagnosis of pseudomesotheliomatous (PMC) carcinoma because a sufficient amount of tissue can be obtained for diagnosis. This is the first report of PMC diagnosed using EUS-B-FNA. Our findings suggest that EUS-B-FNA may reduce the risk of dissemination for PMC.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Thoracic mesenchymal malignant tumors and programed cell death ligand-1 status: Clinicopathologic and prognostic analysis of eight pulmonary sarcomatoid carcinomas and eight malignant mesotheliomas. K. Otsubo, H. Sakai, H. Kimura, et al. 2021;12(23):3169-3176. PubMed · Publisher · Free full text

Abstract

Background: The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital.

Methods: From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD-L1 status and age, sex, stage, histological type, and prognosis were investigated.

Results: PD-L1-positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD-L1-positive PSC cases, two showed high PD-L1 expression in the vimentin-positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD-L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD-L1 staining in the sarcomatoid survived, whereas the other with negative PD-L1 staining did not.

Conclusion: The present study showed that sarcomatoid carcinoma had a higher PD-L1 expression compared to non-small-cell lung cancer and that both PSC and MPM tended to exhibit PD-L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Amrubicin in previously treated patients with malignant pleural mesothelioma: A phase II study. T. Ikeda, S. Takemoto, H. Senju, et al. 2020;11(7):1972-1978. PubMed · Publisher · Free full text

Abstract

Background: The aim of this study was to assess the efficacy and safety of amrubicin for previously treated malignant pleural mesothelioma.

Methods: The eligibility criteria were: previously treated unresectable malignant pleural mesothelioma; performance status 0-1; age ≤ 75; adequate hematological, hepatic, and renal function. The patients were injected with 35 mg/m2 amrubicin on days one, two, and three every 3-4 weeks. The planned number of patients was 32.

Results: The study was terminated due to delay in enrollment and 10 patients were subsequently enrolled (nine males and one female; median age 67 [range 49-73]), of which four had epithelioid tumors, three had sarcomatoid tumors and three had biphasic tumors, respectively. According to the International Mesothelioma Interest Group (IMIG), one, four, and four patients had stage II, III, and IV, respectively, and one had postoperative recurrence. There was one (10%) partial response, four (40%) had stable disease, and five (50%) patients exhibited disease progression. The overall response and disease control rates were 10% (95% CI: 0.3-44.5%) and 60% (95% CI: 26.2-87.8%), respectively. The median progression-free survival time was 1.6 months. The median overall survival time was 6.6 months, and the one-, two-, and three-year survival rates were 23%, 23%, and 0%, respectively. The observed grade 3 or 4 toxicities included neutropenia in six (60%) patients; leukopenia in five (50%) patients; and febrile neutropenia, thrombocytopenia, anemia, and pneumonia in one (10%) patient each.

Conclusions: There was not enough data to evaluate the efficacy because the study was terminated early. However, amrubicin showed limited activity and acceptable toxicities when used in previously treated malignant pleural mesothelioma patients.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Gender differences in molecular-guided therapy recommendations for metastatic malignant mesothelioma. H. Taghizadeh, S. Zöchbauer-Müller, R.M. Mader, et al. 2020;11(7):1979-1988. PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma is an aggressive cancer and has a poor prognosis. Here, we analyzed the feasibility, molecular and gender aspects of targeted therapy recommendations for malignant mesothelioma based on the individual molecular tumor profile.

Methods: In this single-center, real-world retrospective analysis of our platform for precision medicine, we evaluated the molecular profiling of malignant mesothelioma in 14 patients, including nine men and five women. Tumor samples of the patients were examined with a 50 gene next-generation sequencing (NGS) panel, immunohistochemistry, and fluorescence in situ hybridization, to detect possible molecular aberrations which may be targeted by off-label therapy custom-tailored to the individual patient.

Results: In total, we identified 11 mutations in six of the 14 patients, including BAP1, FANCA, NF1, NF2, PD-L1, RAD52D, SETD2, SRC, and TP53. No mutation was detected in eight of the 14 patients. Targeted therapy was recommended for 11 out of the 14 patients. All recommendations were mainly based on the molecular characteristics determined by immunohistochemistry. Targeted therapy recommendations were significantly more often for men than women due to gender-specific differences in PDGFRα expression. Eventually, four patients received the targeted therapy, of whom one patient subsequently achieved stable disease.

Conclusions: Our observations suggest that a molecular-guided treatment approach is feasible for the management of advanced malignant mesothelioma. Our analysis revealed gender specific differences in PDGFRα expression that should be further evaluated in clinical trials.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Interleukin-5-producing malignant pleural mesothelioma with eosinophilic pleural effusion. E. Takeuchi, N. Takahashi, S. Morizumi, et al. 2020;11(10):3043-3046. Case report PubMed · Publisher · Free full text

Abstract

Malignant tumors are often associated with eosinophilic pleural effusion. Here, we encountered a case of interleukin-5 (IL-5)-producing malignant pleural mesothelioma with eosinophilic pleural effusion. The patient was a 50-year-old male. He had a history of a cough for several weeks and had visited a local doctor. Left pleural effusion was noted, and the patient was referred to our hospital. He was diagnosed with malignant pleural mesothelioma by pleural biopsy, with eosinophilic pleural effusion. IL-5 in the pleural effusion increased, and tumor cells were IL-5-positive by immunostaining. There have been few reports of IL-5-producing tumors, and this is the first report of IL-5-producing malignant pleural mesothelioma. Host-tumor cell interactions cause eosinophilic pleural effusion. In patients with eosinophilic pleural effusion, malignant pleural effusion should be considered. It is necessary to clarify the pathophysiology of malignant tumors and eosinophils.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Locoregional control and toxicity after pleurectomy/decortication and intensity-modulated pleural radiation therapy in patients with malignant pleural mesothelioma. O. Arrieta, F. Lozano-Ruiz, M. Blake-Cerda, et al. 2020;11(12):3448-3455. PubMed · Publisher · Free full text

Abstract

Background: Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM.

Methods: We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields.

Results: A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months.

Conclusions: Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Nucleolin and nucleophosmin expression patterns in pulmonary adenocarcinoma invading the pleura and in pleural malignant mesothelioma. M. Masiuk, P. Waloszczyk, M. Lewandowska, et al. 2020;11(9):2529-2535. PubMed · Publisher · Free full text

Abstract

Background: Visceral pleural invasion (VPI) in adenocarcinoma of the lung is considered a poor prognostic factor. The purpose of this study was to analyze nucleolin and nucleophosmin expression in pulmonary adenocarcinoma (PA) with VPI and in pleural malignant mesothelioma.

Methods: The study was conducted on the basis of 19 pathologically-confirmed cases of adenocarcinoma of the lung and 29 cases of epithelioid malignant mesothelioma. The nucleolin and nucleophosmin expression was assessed immunohistochemically and analyzed with image analysis software.

Results: Nucleolin expression was lower while nucleophosmin was higher in pleural invasion of pulmonary adenocarcinoma than in the central part of the tumor. Differences in subpopulations of cells with different expression of proteins studied were also found. Malignant mesothelioma showed lower nucleolin expression than adenocarcinoma of the lung but no differences in nucleophosmin expression were found.

Conclusions: The results of our study suggested that lower nucleolin and higher nucleophosmin expression may be related to higher invasiveness of adenocarcinoma of the lung. Differences in nucleolin expression between pulmonary adenocarcinoma and malignant mesothelioma indicate another aspect of biology of these pleura-invading cancers that requires further study.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Differences in nucleolin and nucleophosmin expression in pleura invading pulmonary adenocarcinoma indicate the involvement of these proteins in its locoregional spread while differences in nucleolin expression between pulmonary adenocarcinoma and malignant mesothelioma suggest another aspect of biology of these cancers.

What This Study Adds: This is the first study on nucleolin and nucleophosmin expression in pleural malignant mesothelioma and pleura-invading pulmonary adenocarcinoma. Our findings may assist in understanding the mechanisms of locoregional spread of adenocarcinoma and differences between these two pleura-invading cancers.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Simultaneous tongue metastasis from malignant pleural mesothelioma: Case report and literature review. C. Huang, X. Yang. 2020;12(3):391-6. Case report PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare neoplasm of the serosal membranes. MPM usually manifests as local invasion, rarely with distant haematogenous metastases in different organs. Few cases of tongue metastasis have been documented. Here, we report the case of a 68-year-old man diagnosed with malignant pleural epithelioid mesothelioma together with a simultaneous tongue lesion, which was found to be metastatic malignant mesothelioma. Tongue metastasis from MPM is rare and the oral symptoms it causes could be an early sign of clinical manifestation. For patients with oral symptoms and a newly discovered tongue lesion, clinicians should be aware of the possibility of tongue metastasis and search for a primary malignancy.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Single-center study to determine the safety and efficacy of CT-707 in Chinese patients with advanced anaplastic lymphoma kinase-rearranged non-small-cell lung cancer. P. Song, X. Zhang, D. Yang, et al. 2020;11(5):1216-1223. PubMed · Publisher · Free full text

Abstract

Introduction: It has been proven that ALK-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitors while the chemotherapy resistance is unavoidable. In this study, safety and antitumor activity of the novel ALK inhibitor (ALKi) CT-707 were evaluated in Chinese patients with advanced ALK-rearranged NSCLC.

Methods: This single-center, open-label phase I study recruited adult patients with ALK-rearrangement (confirmed by fluorescence in situ hybridization and/or immunohistochemistry) of locally advanced/metastatic malignancies including NSCLC. This study consisted of two parts: dose escalation and dose expansion. CT-707 was administered orally once a day for 21 days.

Results: A total of 13 patients who were treated with CT-707 from 450 to 600 mg (in the dose increasing phase) were enrolled in this trial (two patients were previously treated with crizotinib). There were 12 patients diagnosed with lung adenocarcinoma and one patient with malignant pleural mesothelioma. After treatment, grade 3 diarrhea (600 mg once a day) was found as dose-limiting toxicity (DLT).The most common adverse events included diarrhea (92%), elevated aspartate aminotransferase (61%), elevated alanine aminotransferase (54%), hair loss (38%), and vomiting (31%). The overall response rate was 77% (10/13). Among all patients, four of the five patients who did not receive any treatment, one of the two patients who had received treatments with crizotinib, and five of the six patients who received standard chemotherapy achieved partial response (PR). One patient reached a complete remission (CR).

Conclusions: This study indicated that CT-707 is clinically effective as a new antitumor drug for Chinese lung adenocarcinoma patients with ALK rearrangement. It is safe and reliable and the dose-expansion phase recruitment has started.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Treatment patterns among patients with malignant pleural mesothelioma: An Italian, population-based nationwide study. A. Trama, C. Proto, D. Signorelli, et al. 2020;11(6):1661-1669. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions.

Methods: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department.

Results: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department.

Conclusions: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services.

Key Points: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions.

What This Study Adds: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

2010s

Anaplastic thyroid carcinoma mimicking a malignant pleural mesothelioma: Clues for diagnosis. T. Capron, S. Giusiano, V. Bourinet, et al. 2019;10(11):2175-2178. Case report PubMed · Publisher · Free full text

Abstract

Pleural metastasis of thyroid carcinoma is very rarely encountered in the evaluation of pleural effusion and diagnosis may be challenging. However, an anaplastic transformation of papillary thyroid carcinoma (PTC), although a rare condition, should be considered even after a prolonged period of patient follow-up. Here we report a case of anaplastic thyroid carcinoma mimicking malignant pleural mesothelioma diagnosed nine years after the initial diagnosis of PTC and detail the clues used to orient and confirm the diagnosis.

© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Characteristics and long-term outcomes of advanced pleural mesothelioma in Latin America (MeSO-CLICaP). L. Rojas, A.F. Cardona, R. Trejo-Rosales, et al. 2019;10(3):508-518. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population.

Methods: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients.

Results: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders.

Conclusion: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.

© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Survival analysis via nomogram of surgical patients with malignant pleural mesothelioma in the Surveillance, Epidemiology, and End Results database. M. Zhuo, Q. Zheng, Y. Chi, et al. 2019;10(5):1193-1202. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates from the pleura and has a poor prognosis. Eligible patients can benefit from surgery, but their survival is affected by many factors. Therefore, we created a graphic model that could predict the prognosis of surgically treated patients.

Methods: We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results database from 2004 to 2014 to identify the key factors affecting the prognosis of surgically treated MPM patients. On this basis we built a nomogram to predict survival. We then evaluated the performance of the nomogram in a validation cohort.

Results: In a training cohort of 828 cases, independent prognostic factors, including age, gender, histological type, differentiation, N stage, chemotherapy, type of surgery, and lymph node dissection, were identified. We then developed a nomogram to evaluate individual patient survival. In Kaplan-Meier analysis, a higher score in the nomogram was associated with a worse prognosis. We also used a validation cohort consisting of 312 patients to evaluate the performance of the nomogram, which was well calibrated and had good discrimination ability, with concordance indices of 0.715 and 0.656 for the training and validation cohorts, respectively.

Conclusion: This study has improved our understanding of resected MPM and shown that key factors, including age and histological type, are associated with overall survival. The nomogram is a reliable tool that can help clinicians turn individualized prediction into reality and maximize patient benefit by identifying the most beneficial treatment approach.

© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Intensity-modulated radiotherapy is a safe and effective treatment for localized malignant pleural mesothelioma. M. Simon, T. Shochat, N. Peled, et al. 2018;9(11):1470-1475. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare disease and management of localized disease is controversial. Radiotherapy has been shown to be useful after extrapleural pneumonectomy (EPP), as well as with less aggressive surgery. As no reports of the treatment of this disease have ever been published from Israel, we report our experience with MPM and intensity-modulated radiotherapy (IMRT).

Methods: The complete medical records of patients treated for MPM at the Rabin Medical Center from 1 August 2007 to 31 March 2016 were reviewed. Twenty-seven patients were treated with IMRT, either post-EPP or without EPP. Patients received 54 Gy in 2 Gy fractions using the restricted field IMRT technique. Chemotherapy was administered sequentially in 26% of patients. Patients were followed up from the date of diagnosis to death or treatment failure.

Results: Seventy-eight percent of patients had the epithelioid subtype. Nearly all patients were male (85%) and 90% of non-surgical patients were administered chemotherapy compared to 56% of post-EPP patients. All patients completed therapy and only 16% had grade 1-2 radiation pneumonitis, with no incidence of grade 3 or higher. The median follow-up was 22 months and the mean overall survival was 34.9 months. The mean time to progression following radiation therapy was 26.7 months. The mean time to local and distant failure was 19 and 16 months, respectively.

Conclusions: IMRT for localized pleural mesothelioma is a tolerable and effective therapy both post-EPP or without surgery. These results suggest that future investigation in this area is required.

© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Overexpression of micro ribonucleic acid-591 inhibits cell proliferation and invasion of malignant pleural mesothelioma cells. S. Cheng, Y. Xu, Z. Shi, et al. 2016;7(3):340-7. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer refractory to current therapies. Reduced expression of micro ribonucleic acid (miR)-591 in a range of cancer types has suggested it is a potent tumor suppressor, and overexpression has been shown to inhibit tumor cell growth. The role of miR-591 in MPM is largely unknown.

Methods: miR-591 was over-expressed in vitro using micro RNA mimics in three MPM cell lines (H513, H2052, H2373), and effects on tumor cell growth, proliferation, invasion, and target gene expression were assessed.

Results: miR-591 mimic was introduced into MPM cell lines to overexpress this microRNA. The cellular growth, proliferation, and invasive capability was significantly inhibited after overexpression of miR-591. Growth inhibition caused by miR-591 correlated with upregulation of p21 and Bax. Reduced invasive capability correlated with downregulation of matrix metalloproteinase-2 and transforming growth factor-β1.

Conclusion: miR-591 is a potent tumor suppressor in MPM. Overexpression of miR-591 may represent a novel therapeutic approach for MPM.
Retrospective analysis of unknown primary cancers with malignant pleural effusion at initial diagnosis. T. Ebata, Y. Okuma, Y. Nakahara, et al. 2016;7(1):39-43. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural effusion (MPE) can occur during the progression of various cancers. However, factors, such as the incidence of MPE associated with different types of cancers and its potential for diagnosing previously undetected cancers, are unknown. Moreover, MPE may accompany potentially curable cancers or those with a favorable survival prognosis with adequate treatment. The present study determined the types of cancers accompanied by MPE at initial diagnosis and investigated appropriate related methods for diagnosing previously unknown cancers.

Methods: We retrospectively reviewed the medical records of 35 patients with MPE at initial cancer diagnosis between 2004 and 2012. We evaluated the patient characteristics, final diagnosis, and diagnostic processes.

Results: Of the 35 patients, 10 had lung cancer, seven ovarian or peritoneal cancer, four malignant pleural mesothelioma, one breast cancer, one lymphoma, one pancreatic cancer, and 11 had cancers of unknown origin. Diagnoses of the primary lesions were confirmed using the MPE cellblock method for seven of 11 patients (63.6%), by excisional biopsy or aspiration from other sites in four of nine patients, by exploratory laparotomy in two of three patients, and by peritoneal washing cytology in five patients.

Conclusion: Lung cancer and cancer of unknown origin are major causes of MPE at initial presentation. However, these groups also contain cancers that are curable and those with good long-term prognosis. The MPE cellblock method represents an accurate method for identifying cancer origin.
Granulocyte-colony stimulating factor (G-CSF) producing malignant pleural mesothelioma: Report of a case. A. Fujiwara, M. Higashiyama, T. Kanou, et al. 2015;6(1):105-9. PubMed · Publisher · Free full text

Abstract

This report presents a case of malignant pleural mesothelioma (MPM) producing granulocyte colony-stimulating factor (G-CSF) that was treated by tumor resection. A 76-year-old male presented with a huge right-side chest wall tumor, along with a slight fever and chest wall pain. Laboratory findings showed an increased white blood cell count (64600 cells/μL) and C-reactive protein level (20.57 mg/dL). The patient underwent surgical removal of the tumor along with tissue from the chest wall and histopathological analysis led to a diagnosis of sarcomatous type of MPM. Immunohistochemical findings for both anti-human G-CSF and interleukin-6 monoclonal antibodies were positive. Although the general condition of the patient quickly improved after surgery, local recurrence occurred two months later and he died of respiratory failure seven months after the operation, though surgery provided symptom relief. G-CSF-producing MPMs usually show a poor prognosis, though less-invasive surgery may be considered for relief of symptoms.
Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case. M. Kohno, R. Maruyama, D. Kitagawa, et al. 2014;5(1):74-7. PubMed · Publisher · Free full text

Abstract

This report describes a rare case of localized malignant biphasic (mixed epithelioid and sarcomatoid) mesothelioma arising in the peritoneum. A 69-year-old male with a history of asbestos exposure, complaining of a painful mass in the left chest wall, was found via computed tomography (CT) to have a tumor in the left peritoneum. The resected tumor was histologically and immunohistochemically consistent with a malignant mesothelioma with mixed epithelioid and sarcomatoid type and no distant metastasis. The diagnosis of localized malignant biphasic mesothelioma arising in the peritoneum was appropriate because there was no evidence of any other primary tumor.
Treatment for recurrence after extrapleural pneumonectomy for malignant pleural mesothelioma: A single institution experience. T. Okamoto, T. Yano, A. Haro, et al. 2013;4(1):66-70. PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma (MPM) is a relatively rare, aggressive neoplasm associated with asbestos exposure. Extrapleural pneumonectomy (EPP) is often performed for resectable MPM as part of a multidisciplinary treatment; however, available data on treatments for recurrence after EPP are limited.

Methods: The clinical records of consecutive MPM patients who underwent EPP at our institution from 2001 to 2010 were retrospectively reviewed. There were 10 patients who underwent EPP with or without perioperative chemotherapy; of these, recurrence was observed in eight patients.

Results: The overall median survival time and time to recurrence were 49.6 months and 15.4 months, respectively, after EPP. The first recurrence occurred within the ipsilateral thorax in four patients. These patients all underwent local treatments for their recurrence, including surgery or radiotherapy and with or without systemic chemotherapy. Other first recurrences were seen in the peritoneal space of two patients and in the contralateral lung of two patients. These patients received platinum-based systemic chemotherapy for their recurrence. The median survival time after the first recurrence was 17.8 months, and the 2-year survival rate was 23.4%.

Conclusions: Most patients who underwent EPP developed tumor recurrences. Direct tumor extension may be a major mechanism of recurrence. Aggressive treatment for recurrent MPM after EPP, including locoregional control and/or systemic chemotherapy, was important for achieving long-term survival.

© 2012 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd.
Clinical and biologic prognostic factors in malignant pleural mesothelioma. V. Ambrogi, T.C. Mineo, Multidisciplinary Tor Vergata University Study Group for Malignant Pleural Mesothelioma. 2012;3(4):289-302. Review PubMed · Publisher

Abstract

Malignant pleural mesothelioma is an extremely aggressive neoplasm of the pleura mainly attributable to asbestos exposure. Conventional medical, physical, and surgical treatments and their combinations are basically ineffective and just a few subjects experience some benefit. No definite guidelines can be provided in patient selection and therapeutic strategies. Currently, malignant pleural mesothelioma therapy is guided by clinical stage and patient characteristics, which are quite unreliable, rather than by the histological or molecular features of the tumor. In the present review the impact on prognosis of classic (i.e. etiology, age, gender, histology, staging), as well as relatively new clinical factors such as quality of life, positron emission tomography assessment, and occult residual disease, are firstly evaluated. In the second section of the review several biological variables and genetic markers, which have been recently recognized as the bases of the disease onset and development, are listed and discussed. There are serum and tissue markers. The latter are mainly related to cell cycle regulation, apoptosis, and growth factor pathways. These novel factors may play an important role in defining the prognosis of the disease and, subsequently, may have a place in addressing therapy.

© 2012 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty. Ltd.
Malignant pleural mesothelioma: A retrospective analysis of clinicopathological and survival data. A.M. Adel, Z.M. Abdel Hafeez, E.T. El Sheikh, et al. 2011;2(1):16-23. PubMed · Publisher

Abstract

Background: The aim of this study was to analyze the clinicopathological features of malignant pleural mesothelioma (MPM) and evaluate the therapeutic measures offered to patients with MPM and their impact on survival.

Methods: Data was retrospectively collected from the medical records of 304 patients who presented to the Department of Clinical Oncology and Nuclear Medicine, Ain Shams University between January 2003 and December 2008.

Results: The mean age of patients was 52.1 years (range 24-87 years). One hundred and ninety patients (62.5%) came from endemic areas and/or gave history of occupational asbestos exposure. One hundred and sixty-nine patients received chemotherapy. There was a significant difference between the median survival for patients who received chemotherapy (9 months, 95% CI 7.69-10.30) and those who were offered best supportive care (2 months, 95% CI 0.09-3.91). Other factors that affected the survival negatively were: non-epithelial pathology (P= 0.001); age >50 years (P= 0.012); bad performance status (P= 0.001); non-platinum based chemotherapy (P= 0.0001); and progressive disease (P= 0.000). Cox regression analysis revealed that the factors that predicted shorter survival were patients being offered best supportive care rather than chemotherapy and progressive disease.

Conclusion: MPM is a growing health problem in Egypt that needs more attention. The current analysis of data reflects the importance of maintaining a high index of suspicion to allow for early diagnosis, especially for cases that live in areas with high asbestos exposure and for people who work in occupations that expose them to asbestos as well as their family members. Prospective randomized trials comparing multimodality approaches to other forms of treatment and including quality of life assessment are warranted.

© Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.
Deposition and cellular interaction of cancer-inducing particles in the human respiratory tract: Theoretical approaches and experimental data. R. Sturm. 2010;1(4):141-152. Review PubMed · Publisher

Abstract

Inhaled particles that are deposited on the epithelial surface of the human respiratory tract (HRT) may act as serious health hazards, in the worst case inducing the development of various types of lung cancer. In the past, several particle types, such as asbestos fibers, hard wood dust and cigarette smoke were identified and classified as human carcinogens. Due to their different physical and chemical properties these particles are characterized by remarkable discrepancies concerning their transport, deposition, and epithelial interaction in the HRT. In order to continuously increase the knowledge on carcinogenic particle behavior in the HRT, theoretical models describing single stages of particulate action in the lung airways were developed over the last few decades. With the help of these mathematical approaches physical characteristics of aerosolized drugs as well as protocols of inhalative therapies for the treatment of lung diseases could be significantly optimized. In addition, new experimental setups for the enlightenment of possible mechanisms underlying particle-lung interaction were, among other things, founded upon the results of theoretical computations. This review summarizes the efforts and advances of theoretical lung modeling from the early 1970s till today, thereby mainly directing the attention to the simulation of carcinogenic particle behavior in the HRT.

© Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.
Management of malignant pleural mesothelioma. P. Hürmüz. 2010;1(2):53-61. Review PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a rare neoplasm arising from the surface serosal cells of the pleural cavity. More than 80% of cases of malignant pleural mesothelioma have been attributed to asbestos exposure. In its natural course median survival is 4 to 12 months. If untreated most of patients die due to local complications of the disease. Surgery improves local control but is not sufficient as a single treatment modality. The recommended treatment strategy for a select group of patients is multimodal therapy that includes surgery, radiotherapy and chemotherapy.

© Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.
Theoretical approach to the hit probability of lung-cancer-sensitive epithelial cells by mineral fibers with various aspect ratios. R. Sturm. 2010;1(3):116-125. PubMed · Publisher

Abstract

Background: Inhalation of fibers may lead to the damage and, as a further consequence, to the malignant transformation of specific (most of all non-ciliated) cells of the bronchial and bronchiolar airway epithelium. In order to accurately estimate the cancer risk induced by inhaled fibers, hit probabilities of non-ciliated (secretory) cells by mineral fibers (asbestos and chrysotile) were computed.

Methods: Besides the use of a stochastic lung geometry and a particle transport/deposition model being based upon the random-walk algorithm, histological data of cell distributions in the human lungs were applied for the theoretical calculations. Diameters of computer-generated fibers ranged from 0.1 µm to 10 µm, whilst two values (3 and 100) were selected for the aspect ratios (ratios of fiber length to fiber diameter), thereby simulating the behavior of short and very long fibrous particles.

Results: According to the modeling results, the highest regional hit probabilities (up to 10%) are available for fibers with a diameter of 1.0 µm, whereby cells of the bronchiolar compartment represent a preferential target of these particles. For fibers with a diameter of 0.1 µm, bronchiolar hit probabilities reach 2-3%, whereas fibers with a diameter of 10 µm penetrate to the peripheral lung parts with only low amounts (<0.1%). A change of the inhalation conditions from sitting to light-work breathing enhances the extrathoracic and bronchial filtering of large particles (diameter ≥1 µm), whilst penetration of small particles towards distal lung airways is subject to a reinforcement. Further refinement of hit probabilities by considering single airway generations results in the circumstance that fibers with diameters ≤1.0 µm preferably collide with cancer-sensitive cells of airway generations 12-15. In contrast, fibers with a diameter of 10 µm mainly represent a hazard for cancer-sensitive cells being located in the uppermost airways. A change of breathing conditions both supports the effect of short fibers and enhances the filtering of long ones.

Conclusion: Based upon the results of this contribution it can be concluded that highest cancer risk is generated by the inhalation of mineral fibers with diameters ≤1.0 µm, whereby fiber length has to be classified as a parameter with lower importance.

© Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.

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