Cancer Medicine

Our medical research library holds 32 studies published in Cancer Medicine (2013–2026). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 31 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: John Wiley & Sons Ltd
• Published: 2012 to the present, United States
• Language: English
• ISSN: 2045-7634 (electronic)
• Its record in the NLM Catalog

2020s

• Adverse Renal Outcomes in Patients With Mesothelioma-A Territory-Wide Real-World Data. W.C. Kwok, J.C.M. Ho, I.S.H. Leung, et al. 2026;15(2):e71595. PubMed · Publisher · Free full text

  Abstract

  Introduction: Advances in mesothelioma management have translated into longer patient survival and different treatment-related side effects including nephrotoxicity. The risk of developing adverse renal outcomes in patients with mesothelioma and associated risk factors remains undefined.

  Methods: We analysed territory-wide data from electronic health records of patients with mesothelioma followed at public hospitals in Hong Kong between 1st January 2000 to 31st December 2022. Prevalence of acute kidney injury (AKI), renal progression (> 30 mL/min drop in eGFR), and upstaging of chronic kidney disease (CKD) and associated risk factors were evaluated.

  Results: 222 patients were included. 18 (5.1%) patients developed acute kidney injury (AKI), and risk factors included diabetes mellitus (DM), use of bevacizumab and the presence of third space fluid (pleural effusion, pericardial effusion, ascites). 47 (21.2%) patients had upstage of CKD, and 31 (14.0%) patients showed renal progression. 18, 9, and 4 patients developed renal progression within 12 months from diagnosis, 12-24 months from diagnosis, and more than 24 months from diagnosis. Risk factors for upstage of CKD included the presence of third space fluid, platinum-based chemotherapy, use of immune check-point inhibitors, AKI during follow-up, more lines of cytotoxic chemotherapy received, and cycles of pemetrexed used. Predictors for renal progression included the presence of ascites and use of bevacizumab.

  Conclusion: Short- and long-term adverse kidney outcomes are prevalent in patients with mesothelioma and show strong associations with treatments received. Careful patient selection and close monitoring of renal function may help avoid untoward acute and chronic nephrotoxicity.

  © 2026 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

• Cancer Risk Prediction Using Machine Learning for Supporting Early Cancer Diagnosis in Symptomatic Patients: A Systematic Review of Model Types. F. Pennisi, S. Borlini, H. Harrison, et al. 2025;14(24):e71463. Systematic review PubMed · Publisher · Free full text

  Abstract

  Introduction: Predictive models could support clinicians in identifying patients who may benefit from cancer investigations. We aimed to examine published evidence on machine learning models (ML) developed to estimate cancer risk based on symptoms and other patient characteristics.

  Methods: Using MEDLINE, Scopus, and EMBASE, we performed a systematic review of studies published in 2014-2024, which included data on signs/symptoms for cancer risk prediction. We used the QUADAS-AI tools to assess study quality. We performed a quantitative synthesis of diagnostic performance, including accuracy, sensitivity, specificity, area under the curve (AUC). Adherence to TRIPOD guidelines was assessed.

  Results: Among the 5646 initially identified articles, 34 met inclusion criteria. Included studies most frequently examined lung (n = 9 studies), mesothelioma (n = 7), and gastrointestinal cancers (n = 4) and used hospital electronic health records (n = 8) or publicly available online datasets (n = 13). In addition to signs/symptoms (n = 34), most models included sociodemographic characteristics (n = 27) and lifestyle factors (n = 20). In 70% of studies, internal validation was performed. ML models demonstrated variable performance, with AUC values ranging from 0.60 to 1 during validation. Random Forest, Support Vector Machine, Decision Tree, and Multilayer Perceptron showed the best predictive performance. Most of the studies (94.1%) had a high risk of bias for the index test.

  Conclusion: ML models have been reported to demonstrate potential in managing complex data for cancer risk prediction. However, the current evidence is heterogeneous and frequently limited by bias and incomplete reporting. Further validation and thorough assessments of real-world performance are necessary before these models can be considered reliable for clinical use.

  Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42024548088.

  © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

• Estimating Cancer Penetrance in Carriers of BRCA2 Pathogenic Variants Using Cancer-Specific Polygenic Scores. B. Prassas, Z. Shi, H. Tran, et al. 2025;14(11):e70990. PubMed · Publisher · Free full text

  Abstract

  Introduction: BRCA2 is a causal gene for hereditary breast and ovarian cancer (HBOC) syndrome. However, its association with other cancers and interplay with polygenic scores (PGS) remains unclear.

  Methods: An observational cohort study for the diagnosis of various cancers in the UK Biobank (UKB, N = 453,541) were recruited at ages of 40-69 years Association of germline pathogenic variants (PVs) in BRCA2 and published cancer-specific PGS with cancer risk was tested using Cox proportional hazards model.

  Results: The median age and interquartile range (IQR) of participants at the analysis was 58.34 (50.60-63.74) years. Carriers of BRCA2 PVs (N = 1629) had a significantly increased risk for four core HBOC-associated cancers (breast, ovarian, pancreatic, and prostate) and six additional types of cancer (lung, oral, small intestine, larynx, liver, and mesothelioma), hazard ratio (HR) > 2.37, all ps < 0.001. For eight cancers where cancer-specific PGS is available, each PGS was significantly associated with its respective cancer risk and independent of BRCA2, HR > 1.25 for 1 unit increase in standard deviation, all ps < 0.001. For female breast and prostate cancer, a significant interaction between BRCA2 and PGS was found (HR < 0.83, p < 0.05); the effect of PGS on cancer risk was weaker in carriers than noncarriers. The probability of cancer by age 75 years (P75) for these 10 cancers increased with higher PGS deciles in both carriers and noncarriers. For several cancers, the P75 in carriers with the lowest PGS decile was lower than that of noncarriers with the highest PGS decile.

  Conclusions: BRCA2 PVs increase risk beyond core HBOC cancers and their risks are modified by cancer-specific PGS. These results suggest that genetic counseling of BRCA2 PV carriers may extend to cancers beyond core HBOC syndrome and incorporate cancer-specific PGS in estimating their penetrance.

  © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

• Global Burden, Projection, and Inequalities Analysis of Cancer Attributable to Occupational Carcinogen Exposure in Individuals Aged Over 40 Years. N. Hu, H. Li, K. Yu, et al. 2025;14(17):e71213. PubMed · Publisher · Free full text

  Abstract

  Background: In this study, we investigated the global burden, projection, and inequalities of cancer attributable to occupational carcinogen exposure in individuals aged over 40 years.

  Methods: Using the Global Burden of Disease 2021 dataset, we examined age-standardized disability-adjusted life years (ASR-DALYs) and deaths associated with cancer attributable to occupational carcinogen exposure. Statistical analyses included: the estimated Annual Percentage Change to assess trends (1990-2021); Bayesian age-period-cohort modeling for projections to 2030 and 2050; decomposition analysis to quantify contributions of aging, population growth, and epidemiological changes; and slope and concentration indices (SII, CI) to evaluate health inequalities by sociodemographic index (SDI).

  Results: In 2021, the global ASR-DALYs attributable to occupational carcinogen exposure were 239.3 per 100,000 (95% uncertainty intervals [UI]: 180.76-300.91), with significant declines found since 1990. The ASR-deaths in the same year were 11.45 per 100,000 (95% UI: 8.57-14.29). By 2050, ASR-DALYs and ASR-deaths are projected to decline to 177.24 and 8.50 per 100,000, respectively. Men exhibited higher DALYs and mortality (3.92 million DALYs, 0.18 million deaths) compared with women. From 1990 to 2021, high SDI regions exhibited the most substantial decline, whereas low-middle SDI regions experienced the highest increase. The most prominent occupational carcinogens were asbestos (ASR-DALYs: 142.36 per 100,000), silica (50.36 per 100,000), and diesel engine exhaust (20.56 per 100,000). Among the seven types of occupational cancers observe, tracheal, bronchial, and lung cancers exhibited the highest ASR-DALY and ASR-deaths. Population growth is the primary contributor to both DALYs and deaths globally, followed by epidemiological changes.

  Conclusion: This study highlights the declining global burden of cancer due to occupational exposure to carcinogens; however, significant disparities persist. Addressing occupational cancer risk in low-SDI regions and under-researched populations is crucial for reducing this health burden.

  © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

• Trends in Pleural Mesothelioma Incidence and Survival in Metropolitan and Nonmetropolitan Areas in the United States. A.J. Didier, C. Lennox, M. Li, et al. 2025;14(24):e71474. PubMed · Publisher · Free full text

  Abstract

  Introduction: Pleural mesothelioma (PM) is a rare, aggressive cancer with significant variation in incidence based on geographic factors. Previous studies have highlighted cancer survival disparities between metropolitan and nonmetropolitan populations for other cancers; this data is largely unreported for PM. We aimed to compare incidence trends and cancer-specific survival (CSS) between metropolitan and nonmetropolitan areas in the United States using the Surveillance, Epidemiology, and End Results (SEER) database.

  Methods: We analyzed SEER 18 registries for patients aged ≥ 20 diagnosed with PM between 2004 and 2021. Incidence rates, CSS, and demographic and clinical characteristics were compared between metropolitan and nonmetropolitan areas. Incidence rate ratios (IRRs) were calculated using the Tiwari method. Joinpoint regression was used to assess temporal trends, while Kaplan-Meier and Cox proportional hazard models analyzed survival outcomes.

  Results: A total of 8519 PM cases were identified, with 89.3% in metropolitan areas. Nonmetropolitan patients were more likely to be non-Hispanic Black and had lower chemotherapy (p = 0.031) and surgery (p < 0.001) rates. The incidence rate in metropolitan areas declined from 1.4 in 2004 to 0.8 in 2021, while nonmetropolitan areas saw a stable incidence until 2017, followed by a decline to 0.5 in 2021. Metropolitan areas had significantly higher CSS, with 50.3% 1-year CSS by 2020, compared to 27.7% in nonmetropolitan areas. Multivariate analysis indicated a higher hazard of death in nonmetropolitan areas (HR = 1.18, p < 0.001).

  Conclusion: Significant disparities in PM outcomes between metropolitan and nonmetropolitan areas were revealed. Although both regions experienced a decline in incidence over time, survival outcomes remained worse in nonmetropolitan areas. Patients in nonmetropolitan areas were also less likely to receive chemotherapy and surgery, further contributing to the survival gap. These findings highlight the need for targeted interventions to improve treatment access and enhance survival for nonmetropolitan patients with PM.

  © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

• Cancer mortality by country of birth and cancer type in Sweden: A 25-year registry-based cohort study. D.N. Tollosa, K. Zendehdel, A. Procopio, et al. 2024;13(14):e70020. PubMed · Publisher · Free full text

  Abstract

  Numerous studies have reported lower overall cancer mortality rates among immigrants compared to native populations. However, limited information exists regarding cancer mortality among immigrants based on specific birth countries and cancer types. We used population-based registries and followed 10 million individuals aged 20 years or older in Sweden between 1992 and 2016. The Cox proportional hazard model was used to explore the disparities in cancer mortality by country of birth and cancer type, stratified by gender. Age-standardized mortality rates were also computed using the world standard population. Hazard ratio (HR) of all-site cancer was slightly lower among immigrants (males: HRm = 0.97: 95% confidence interval: 0.95, 0.98; females: HRf = 0.93: 0.91, 0.94) than Swedish-born population. However, the immigrants showed higher mortality for infection-related cancers, including liver (HRf = 1.10: 1.01, 1.19; HRm = 1.10: 1.02, 1.17), stomach (HRf = 1.39: 1.31, 1.49; HRm = 1.33: 1.26, 1.41) cancers, and tobacco-related cancers, including lung (HRm = 1.44: 1.40, 1.49), and laryngeal cancers (HRm = 1.47: 1.24, 1.75). The HR of mesothelioma was also significantly higher in immigrants (HRf = 1.44: 1.10, 1.90). Mortality from lung cancer was specifically higher in men from Nordic (HRm = 1.41: 1.27, 1.55) and non-Nordic Europe (HRm = 1.49: 1.43, 1.55) countries and lower in Asian (HRm = 0.78: 0.66, 0.93) and South American men (HRm = 0.70: 0.57, 0.87). In conclusion, there are large variations in cancer mortality by country of birth, and cancer type and require regular surveillance. Our detailed analyses lead to some novel findings such as excess mortality rate of mesothelioma and laryngeal cancers in Immigrants in Sweden. A targeted cancer prevention program among immigrants in Sweden is needed.

  © 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

• The incremental healthcare cost associated with cancer in Belgium: A registry-based data analysis. V. Gorasso, S. Vandevijvere, J. Van der Heyden, et al. 2024;13(3):e6659. PubMed · Publisher · Free full text

  Abstract

  Background: Similar to many countries, Belgium experienced a rapid increase in cancer diagnoses in the last years. Considering that a large part of cancer types could be prevented, our study aimed to estimate the annual healthcare burden of cancer per site, and to compare cost with burden of disease estimates to have a better understanding of the impact of different cancer sites in Belgium.

  Methods: We used nationally available data sources to estimate the healthcare expenditure. We opted for a prevalence-based approach which measures the disease attributable costs that occur concurrently for 10-year prevalent cancer cases in 2018. Average attributable costs of cancer were computed via matching of cases (patients with cancer by site) and controls (patients without cancer). Years of life lost due to disability (YLD) were used to summarize the health impact of the selected cancers.

  Results: The highest attributable cost in 2018 among the selected cancers was on average €15,867 per patient for bronchus and lung cancer, followed by liver cancer, pancreatic cancer, and mesothelioma. For the total cost, lung cancer was the most costly cancer site with almost €700 million spent in 2018. Lung cancer was followed by breast and colorectal cancer that costed more than €300 million each in 2018.

  Conclusions: In our study, the direct attributable cost of the most prevalent cancer sites in Belgium was estimated to provide useful guidance for cost containment policies. Many of these cancers could be prevented by tackling risk factors such as smoking, obesity, and environmental stressors.

  © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• A comparative study of diagnostic accuracy in 3026 pleural biopsies and matched pleural effusion cytology with clinical correlation. I.K. Poon, R.C.K. Chan, J.S.H. Choi, et al. 2023;12(2):1471-1481. PubMed · Publisher · Free full text

  Abstract

  Background: Pleural effusion can be caused by a wide range of benign and malignant conditions. Pleural biopsy and effusion cytology represent two key methods of pathological diagnosis. To compare the performance these two methods, a large cohort of matched pleural biopsy and effusion cytology with clinical follow-up was reviewed.

  Methods: Pleural biopsies and effusion cytology specimens over a period of 18 years were retrieved. Cytology specimens collected within 7 days of pleural biopsy were matched. Reports were reviewed, and the cause for pleural effusion was determined by hospital disease coding and clinical data.

  Results: Totally, 3026 cases were included. The leading cause of benign effusion was tuberculosis (n = 650). Malignant pleural effusion (MPE) was more common in older females (p < 0.001) and mostly due to lung cancer (n = 959), breast cancer (n = 64), and mesothelioma (n = 48). The inadequate/insufficient (B1/C1) rate of biopsy was higher than cytology (15.6% vs. 0.3%) but the rates for other diagnostic categories were similar. Biopsy and cytology showed a correlation coefficient of 0.315, improving to 0.449 when inadequate/insufficient (B1/C1) cases were excluded. The ROM for benign cytology (C2) was lower than biopsy (B2) (p < 0.001). Compared with biopsy, the diagnostic accuracy was higher in cytology overall and for metastatic carcinomas (p < 0.001) but lower for hematolymphoid malignancies (p = 0.014) and mesotheliomas (p = 0.002).

  Conclusions: These results suggest that effusion cytology may be better for confirming benignity and diagnosing carcinomatous MPE. In these cases, pleural biopsy may be withheld to reduce procedural risks. However, for suspected hematolymphoid malignancies and mesothelioma, biopsy should be considered.

  © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Aberrant expression of NPPB through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations. T. Sato, K. Akao, A. Sato, et al. 2023;12(12):13586-13598. PubMed · Publisher · Free full text

  Abstract

  Background: Mesothelioma is a neoplastic disease associated with asbestos exposure. It is highly malignant and has a poor prognosis; thus, early detection is desirable. Recent whole-genome analysis has revealed that mesothelioma is characterized by a high frequency of mutations in a set of genes involved in the Hippo pathway, such as NF2 and LATS2. However, a rapid, simple, and precise method for finding mesothelioma with these mutations has not yet been established.

  Methods: Clustering of Hippo pathway gene alteration groups and the differential expression of each gene in mesothelioma patients were analyzed using The Cancer Genome Atlas database. Gene expression levels in various tumors and normal tissues were analyzed using public databases. Knockdown or transient expression of YAP1 or TAZ was performed to evaluate the regulation of gene expression by these genes. NT-proBNP was measured in the pleural effusions of 18 patients and was compared with NF2 expression in five cases where cell lines had been successfully established.

  Results: NPPB mRNA expression was markedly higher in the group of mesothelioma patients with Hippo pathway gene mutations than in the group without them. NPPB expression was low in all normal tissues except heart, and was highest in mesothelioma. Mesothelioma patients in the high NPPB expression group had a significantly worse prognosis than those in the low NPPB expression group. NPPB expression was suppressed by knockdown of YAP1 or TAZ. NT-proBNP was abundant in the effusions of mesothelioma patients and was particularly high in those with impaired NF2 expression.

  Conclusions: NPPB, whose levels can be measured in pleural effusions of mesothelioma patients, has the potential to act as a biomarker to detect NF2-Hippo pathway gene alterations and/or predict patient prognosis. Additionally, it may provide useful molecular insights for a better understanding of mesothelioma pathogenesis and for the development of novel therapies.

  © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Epidemiological, therapeutic, and survival trends in malignant pleural mesothelioma: A review of the National Cancer Database. P. Bou-Samra, A. Chang, F. Azari, et al. 2023;12(11):12208-12220. Review PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer of the cells lining the pleural cavity with a low overall incidence. The National Cancer Database (NCDB) released in August 2022 updated data that reflect the newest trends in MPM.

  Methods: The NCDB was queried for patients diagnosed with MPM between 2004 and 2020. Variables collected included demographics, tumor characteristics, and treatment. Student's t-test and independent-samples proportions test were used for means analysis. Survival was assessed by the Kaplan-Meier method using SPSS version 28.

  Results: A total of 41,074 patients were diagnosed with mesothelioma, with a steady incidence (0.25%) between 2004 and 2017. The mean age of diagnosis was 70 (SD 13). 73.2% of the patients were males, 69% had no comorbidities, and 93.3% were white. More patients were diagnosed at Stage 1 after 2008 (p < 0.001). Since 2010, there has been a significant increase in patients offered treatment with 73.9% receiving some therapy (p < 0.01): 50.5% received chemotherapy, 27.6% surgery, 8.6% radiation, and 5.4% immunotherapy. The median overall survival was 10.3 months from diagnosis [95% CI: 10.2-10.5]. Risk factors associated with 30-day mortality from surgical intervention included age (OR = 1.02, p < 0.001), male gender (OR = 1.3, p = 0.03), poorly differentiated grade (OR = 2.1, p < 0.001), Stage 4 (OR = 1.4, p = 0014), and epithelioid histology (OR = 0.51, p = 0.03).

  Conclusion: The current management of MPM is based on stage and histologic subtype. Due to the small numbers of patients at most academic centers, the NCDB provides a robust dataset to draw upon broad data points in treatment discussions with patients.

  © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Five-year survival and clinical correlates among patients with advanced non-small cell lung cancer, melanoma and renal cell carcinoma treated with immune check-point inhibitors in Australian tertiary oncology centres. L.J. Brown, I.P. da Silva, T. Moujaber, et al. 2023;12(6):6788-6801. PubMed · Publisher · Free full text

  Abstract

  Aims: There is robust trial evidence for improved overall survival (OS) with immunotherapy in advanced solid organ malignancies. The real-world long-term survival data and the predictive variables are not yet known. Our aim was to evaluate factors associated with 3-year and 5-year OS for patients treated with immune checkpoint inhibitors (ICIs).

  Methods: We performed a retrospective study of patients who received ICIs as management of advanced solid organ malignancies in two tertiary Australian oncology centres from 2012-2017. Data pertaining to clinical characteristics, metastatic disease burden, immune-related adverse events (IRAEs) and tumour responses were collected and their relationship to survival examined.

  Results: In this analysis of 264 patients, 202 (76.5%) had melanoma, 46 (17.4%) had non-small cell lung cancer (NSCLC), 12 (4.5%) had renal cell carcinoma (RCC) and 4 (1.5%) had mesothelioma. The 5-year OS rates were 42.1% in patients with melanoma, 19.6% with NSCLC, 75% with RCC, and none of the mesothelioma patients were alive at 5 years. In multivariate analysis, an ECOG score of 0 (Hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.23-0.66; p < 0.001) and the occurrence of IRAE's of any grade (HR 0.61; 95% CI 0.37-0.95; p = 0.05) were associated with better 5-year survival. The presence of bone metastases (HR 1.62; 95% CI 1.03-2.82; p = 0.05) and liver metastases (HR 1.76; 95% CI 1.07-2.89; p = 0.03) were associated with worse 5-year survival.

  Conclusions: These results support the long-term benefits of immunotherapy that in some patients, extend to at least 5 years. ECOG performance status of 0 and the occurrence of irAEs are associated with better long-term survival. Survival is significantly influenced by metastatic site and cancer type. These predictive clinical correlates aid discussions and planning in the delivery of ICIs to patients.

  © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Immune checkpoint gene VSIR predicts patient prognosis in acute myeloid leukemia and myelodysplastic syndromes. K. Yao, E. Zhou, E. Schaafsma, et al. 2023;12(5):5590-5602. PubMed · Publisher · Free full text

  Abstract

  Background: Immune checkpoint proteins play critical functions during the immune response to cancer and have been targeted by immune checkpoint blockade therapy. V-domain Ig suppressor of T cell activation (VSIR) is one of these immune checkpoint genes and has been investigated extensively in recent years due to its conflicting roles in cancer immunity. Specifically, in acute myeloid leukemia (AML), the prognostic value of VSIR is debated.

  Results: In both patient tumor samples and cancer cell lines we find that VSIR has the highest expression in AML out of all cancer types and, in AML, has the highest expression out of all other immune checkpoint genes. Survival analysis indicated that AML patients with higher VSIR expression have significantly shorter survival than those patients with lower expression, even within established AML subgroups (e.g., FAB subtypes). Importantly, VSIR expression is predictive of progression from myelodysplastic syndromes (MDS) patients into AML, suggesting its potential role during the very early stage of AML development and progression. In addition to AML, VSIR also demonstrates prognostic values in other cancer types, including multiple myeloma and mesothelioma.

  Conclusion: In summary, our analyses revealed the prognostic value of VSIR and its potential as a target for immunotherapy, especially in AML.

  © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Individualized prediction of survival benefit from postoperative radiotherapy for patients with malignant pleural mesothelioma. Y. Wo, Y. Peng, Z. Wu, et al. 2023;12(11):12452-12461. PubMed · Publisher · Free full text

  Abstract

  Objectives: The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not been fully verified. We aimed to develop an individualized prediction model for identifying optimal candidates for PORT among MPM patients who received surgery plus chemotherapy and externally validate the performance of the new TNM staging scheme.

  Materials And Methods: Detailed characteristics of MPM patients during 2004-2015 were retrieved from SEER registries. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics (age, sex, histologic type, stage, and type of surgery) between the PORT group and no-PORT group. A novel nomogram was constructed based on independent prognosticators identified by multivariate Cox regression model. The discriminatory performance and degree of calibration were evaluated. We stratified patients into different risk groups according to nomogram total scores and estimated the survival benefit of PORT in different subgroups in order to identify the optimal candidates.

  Results: We identified 596 MPM patients, among which 190 patients (31.9%) received PORT. PORT conferred significant survival benefit in the unmatched population, while there was no significant survival difference favoring PORT in the matched population. The C-index of the new TNM staging scheme was closed to 0.5, which represented a poor discriminatory ability. A novel nomogram was constructed based on clinicopathological factors, including age, sex, histology, and N stage. We stratified patients into three risk groups. Subgroup analyses indicated that PORT was beneficial for high-risk group (p = 0.003) rather than low-risk group (p = 0.965) and intermediate-risk group (p = 0.661).

  Conclusion: We established a novel predictive model, which could make individualized prediction of survival benefit of PORT for MPM and could compensate for weakness in TNM staging system.

  © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Prognostic risk assessment model for alternative splicing events and splicing factors in malignant pleural mesothelioma. Y. Jiang, C. Zhang, Y. Chen, et al. 2023;12(4):4895-4906. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a rare and highly malignant thoracic tumor. Although alternative splicing (AS) is associated with tumor prognosis, the prognostic significance of AS in MPM is unknown.

  Methods: Transcriptomic data, clinical information, and splicing percentage values for MPM were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analyses were performed to establish a model affecting the prognosis of MPM. Survival and ROC analyses were used to test the effects of the prognostic model. LASSO/multivariate Cox analysis was used to construct the MPM prognostic splicing factor (SF) model. The SF-AS interaction network was analyzed using Spearman correlation and visualized using Cytoscape. The association between the MPM prognostic SF model and drug sensitivity to chemotherapeutic agents such as cisplatin was analyzed using pRRophetic.R.

  Results: The LASSO/multivariate Cox analysis identified 41 AS events and 2 SFs that were mostly associated with survival. Nine prognostic prediction models (i.e., seven types of AS model, total AS model, and SF model) were developed. An MPM prognostic SF-AS regulatory network was subsequently constructed with decreased drug sensitivity in the SF model high-risk group (p = 0.025).

  Conclusion: This study provides the first comprehensive analysis of the prognostic value of AS events and SFs in MPM. The SF-AS regulatory network established in this study and our drug sensitivity analysis using the SF model may provide novel targets for pharmacological studies of MPM.

  © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Trend and projection of larynx cancer incidence and mortality in China from 1990 to 2044: A Bayesian age-period-cohort modeling study. E. Ye, J. Huang, J. Wang, et al. 2023;12(15):16517-16530. PubMed · Publisher · Free full text

  Abstract

  Background: Larynx cancer is one of the most common cancers in head and neck, and imposes heavy burden on individual and societies. A comprehensive understanding of the burden of larynx cancer is necessary to improve prevention and control strategies. However, the secular trend of larynx cancer incidence and mortality in China remains unclear.

  Methods: The incidence and deaths rates of larynx cancer from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database. The temporal trend of larynx cancer was analyzed using a joinpoint regression model. The age-period-cohort model was used to explore the age, period, and cohort effects on larynx cancer and predict future trends up to 2044.

  Results: From 1990 to 2019, the age-standardized incidence rate of larynx cancer in China increased by 1.3% (95% CI 1.1 to 1.5) in males, but decreased by 0.5% (95% CI -0.1 to 0) in females. The age-standardized mortality rate of larynx cancer in China decreased by 0.9% (95% CI -1.1 to -0.6) and 2.2% (95% CI -2.8 to -1.7) in males and females, respectively. Among the four risk factors, smoking and alcohol use contributed to a heavier burden compared to occupational exposure to asbestos and sulfuric acid with respect to mortality. Age effects showed that the incidence and deaths of larynx cancer were concentrated in people older than 50 years old. Period effects exerted the most significant effect on larynx cancer incidence for males. In terms of cohort effects, people born in the earlier cohorts presented a higher risk of larynx cancer compared with the later cohorts. From 2020 to 2044, the age-standardized incidence rates of larynx cancer continued to increase in males, whereas the age-standardized mortality rates continued to decrease in both males and females.

  Conclusion: The burden of larynx cancer in China has a significant gender difference. The age-standardized incidence rates will continue to increase in males up to 2044. The disease pattern and risk factors of larynx cancer should be comprehensively studied to promote the development of timely intervention measures and relieve the burden effectively.

  © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Utility of BerEp4/calretinin and desmin/epithelial membrane antigen (EMA) dual immunocytochemical staining in effusion cytology. A. Hjerpe, E. Demir, S. Abd-Own, et al. 2023;12(5):5334-5340. PubMed · Publisher · Free full text

  Abstract

  Background: Pleural mesothelioma (PM) is typically diagnosed late during the disease. Earlier detection can increase the chance of effective therapy. Recurrent pleural effusions are the earliest symptoms displaying an array of cytomorphological changes from reactive atypia to malignancy. Diagnosis is possible on effusion cytology by applying molecular and immunocytochemical markers, the main difficulty being when to suspect PM and to differentiate PM from metastatic adenocarcinoma and reactive mesothelial proliferations.

  Methods: We evaluated the diagnostic performance of two immunocytochemical dual stains (BerEp4/Calretinin and Desmin/Epithelial Membrane Antigen (EMA)) on 149 ethanol-fixed cytospin preparation as an initial step to solve the mentioned diagnostic difficulty. The immunocytochemical reactivity pattern was evaluated by two independent investigators. The final diagnosis corresponded to PM (n = 20), metastatic adenocarcinoma (n = 83), and mesotheliosis (n = 46) in these cases.

  Results: Calretinin had 99% specificity and 98% sensitivity for indicating a mesothelial phenotype, while BerEp4 distinguished the adenocarcinoma cases with 98% specificity and 99% sensitivity. EMA displayed 96% specificity and 99% sensitivity in malignant cases, while Desmin without EMA present showed 99% specificity and 96% sensitivity for indicating benign mesothelial proliferation.

  Conclusions: Interpretation of the four immunoreactions is improved when performed as dual stains. The dual staining is a useful tool in the initial handling of atypical effusions and guides the subsequent choice of antibody panels for more detailed subclassification of malignant effusions.

  © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Re: Comment to "Relationship between exposure to ionizing radiation and mesothelioma risk: A systematic review of the scientific literature and meta-analysis": Cancer Med. 2022 Feb;11(3):778-789. doi:10.1002/cam4.4436. Epub 2022 Jan 14: Cancer Med. 2022 Feb;11(3):778-789. doi:10.1002/cam4.4436. Epub 2022 Jan 14. G. Visci, C. Zunarelli, P. Boffetta, et al. 2022;11(24):5035-5036. Letter · Comment PubMed · Publisher · Free full text

• Relationship between exposure to ionizing radiation and mesothelioma risk: A systematic review of the scientific literature and meta-analysis. G. Visci, E. Rizzello, C. Zunarelli, et al. 2022;11(3):778-789. Meta-analysis · Systematic review PubMed · Publisher · Free full text

  Abstract

  Background: Ionizing radiation and mesothelioma have been examined among personnel employed in nuclear power plant and patients treated by external beam radiation therapy (EBRT). The association is still controversial; the purpose of this review is to summarize the scientific evidence published in the literature regarding the relationship between ionizing radiation and incidence of mesothelioma and, if possible, estimating strongness of the association by meta-analysis of extracted data.

  Methods: Articles included in the systematic review were retrieved by searching among the three main scientific databases: PubMed, Scopus, and Embase. The literature search was conducted in June 2021. A meta-analysis of random effects was conducted, stratified by exposure (EBRT, occupational exposure). The heterogeneity of the summary relative risks (RRs) was assessed using I2 statistics. Publication bias was evaluated graphically through the funnel plot.

  Findings: The exposure to ionizing radiation could be a risk factor for mesothelioma: both for exposure to high doses for short periods (EBRT) (RR of 3.34 [95% confidence interval, CI 1.24-8.99]) and for exposure to low doses for a prolonged duration (exposure working) (RR of 3.57 [95% CI 2.16-5.89]).

  Conclusions: Despite the low number of mesotheliomas in the general population, the steadily increased risk among individuals exposed to radiation is still worth considering.

  © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Identification of prognostic and bone metastasis​-related alternative splicing signatures in mesothelioma. R. Huang, Z. Zheng, S. Liu, et al. 2021;10(13):4478-4492. PubMed · Publisher · Free full text

  Abstract

  Mesothelioma (MESO) is an infrequent tumor derived from mesothelial cells of pleura, peritoneum, pericardium, and tunica vaginalis testis. Despite advancement in technologies and better understanding of tumor progression mechanism, the prognosis of MESO remains poor. The role of alternative splicing events (ASEs) in the oncogenesis, tumor metastasis and drug resistance has been widely discussed in multiple cancers. But the prognosis and potential therapeutic value of ASEs in MESO were not clearly studied by now. We constructed a prognostic model using RNA sequencing data and matched ASE data of MESO patients obtained from the TCGA and TCGASpliceSeq database. A total of 3,993 ASEs were identified associated with overall survival using Cox regression analysis. Eight of them were finally figured out to institute the model by lasso regression analysis. The risk score of the model can predict the prognosis independently. Among the identified 390 splicing factors (SF), HSPA1A and DDX3Y was significantly associated with 43 OS-SEs. Among these OS-SEs, SNX5-58744-AT (p = 0.048) and SNX5-58745-AT (p = 0.048) were significantly associated with bone metastasis. Co-expression analysis of signal pathways and SNX5-58744-AT, SNX5-58745-AT was also depicted using GSVA. Finally, we proposed that splicing factor (SF) HSPA1A could regulate SNX5-58744-AT (R = -0.414) and SNX5-58745-AT (R = 0.414) through the pathway "Class I MHC mediated antigen processing and presentation" (R = 0.400). In this way, tumorigenesis and bone metastasis of MESO were controlled.

  © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• An integrative histopathologic clustering model based on immuno-matrix elements to predict the risk of death in malignant mesothelioma. M.L. Balancin, W.R. Teodoro, C. Farhat, et al. 2020;9(13):4836-4849. PubMed · Publisher · Free full text

  Abstract

  Objective: Previous studies have reported a close relationship between malignant mesothelioma (MM) and the immune matricial microenvironment (IMM). One of the major problems in these studies is the lack of adequate adjustment for potential confounders. Therefore, the aim of this study was to identify and quantify risk factors such as IMM and various tumor characteristics and their association with the subtype of MM and survival.

  Methods: We examined IMM and other tumor markers in tumor tissues from 82 patients with MM. These markers were evaluated by histochemistry, immunohistochemistry, immunofluorescence, and morphometry. Logistic regression analysis, cluster analysis, and Cox regression analysis were performed.

  Results: Hierarchical cluster analysis revealed two clusters of MM that were independent of clinicopathologic features. The high-risk cluster included MM with high tumor cellularity, high type V collagen (Col V) fiber density, and low CD8+ T lymphocyte density in the IMM. Our results showed that the risk of death was increased for patients with MM with high tumor cellularity (OR = 1.63, 95% CI = 1.29-2.89, P = .02), overexpression of Col V (OR = 2.60, 95% CI = 0.98-6.84, P = .04), and decreased CD8 T lymphocytes (OR = 1.001, 95% CI = 0.995-1.007, P = .008). The hazard ratio for the high-risk cluster was 2.19 (95% CI = 0.54-3.03, P < .01) for mortality from MM at 40 months.

  Conclusion: Morphometric analysis of Col V, CD8+ T lymphocytes, and tumor cellularity can be used to identify patients with high risk of death from MM.

  © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• The panoramic picture of pepsinogen gene family with pan-cancer. S. Shen, H. Li, J. Liu, et al. 2020;9(23):9064-9080. PubMed · Publisher · Free full text

  Abstract

  Background: It is well known that pepsinogen (PGs), as an important precursor of pepsin performing digestive function, has a good correlation with the occurrence and development of gastric cancer and it is also known that ectopic PGs expression is related to the prognosis of some cancers. However, the panoramic picture of pepsinogen gene family in human cancer is not clear. This study focused on elucidating the expression profile, activated pathway, immune cells infiltration, mutation, and copy number variation of PGs and their potential role in human cancer.

  Method: Based on the next generation sequence data from TCGA, Oncomine, and CCLE, the molecular changes and clinical correlation of PGs in 33 tumor types were analyzed systematically by R language, including the expression, mutation, and copy number variation of PGs and their correlation with cancer-related signal transduction pathway, immune cell infiltration, and prognostic potential in different cancers.

  Results: PGs expression profiles appear different in 33 tumors. The transcriptional expression of PGs was detected in 16 of all 33 tumors. PGC was highly expressed in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, uterine corpus endometrial carcinoma, bladder urothelial carcinoma and breast cancer, while decreased in stomach adenocarcinoma, kidney renal clear cell carcinoma, prostate adenocarcinoma, lung squamous cell carcinoma, and esophageal carcinoma. PGA3, PGA4, and PGA5 were expressed in most normal tissues, but decreased in cancer tissues. PGs expression was significantly related to the activation or inhibition of many signal transduction pathways, in which PGC and PGA5 are more likely to be associated with cancer-related pathways. PGC participated in 33 regulatory network pathways in pan-cancer, mainly distributed in stomach adenocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma, respectively. PGC and PGA3 expression were significantly correlated with immune cell infiltration. The results of survival analysis showed that different PGs expression play significantly different prognostic roles in different cancers. PGC was correlated with poor survival in brain lower grade glioma, skin cutaneous melanoma, and higher survival in kidney renal clear cell carcinoma, acute myeloid leukemia, mesothelioma, and uveal melanoma. PGA4 was only associated with higher survival in kidney renal clear cell carcinoma. Genetic variation analysis showed that PGC gene often mutated in uterine corpus endometrial carcinoma and stomach adenocarcinoma had extensive copy number amplification in various tumor types. PGC expression was upregulated with the increase of copy number in cholangiocarcinoma, esophageal carcinoma, and kidney renal papillary cell carcinoma, while in stomach adenocarcinoma, PGC was upregulated regardless of whether the copy number was increased or decreased.

  Conclusions: PGs was expressed unevenly in a variety of cancer tissues and was related to many carcinogenic pathways and involved in the immune regulation. PGC participated in 33 regulatory pathways in human cancer. Different PGs expression play significantly different prognostic roles in different cancers. The variation of copy number of PGC gene could affect the PGC expression. These findings suggested that PGs, especially PGC have characteristic of broad-spectrum expression in multiple cancers rather than being confined to the gastric mucosa, which may made PGs be useful biomarkers for prediction/diagnosis/prognosis and effective targets for treatment in human cancer.

  © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

2010s

• Peritoneal mesothelioma in Sweden: A population-based study. P.H. Cashin, G. Jansson Palmer, D. Asplund, et al. 2019;8(14):6468-6475. PubMed · Publisher · Free full text

  Abstract

  The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.

  © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis. C. Chouaid, J.B. Assié, P. Andujar, et al. 2018;7(4):1102-1109. PubMed · Publisher · Free full text

  Abstract

  This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1- and 2-year survival according to sex, age, co-morbidities, management, population-density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co-morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One- and 2-year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7-15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co-morbidities, living in rural/semi-rural area was associated with better 2-year survival (HR: 0.83 [95% CI: 0.73-0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co-morbidities, sex, age, and living place appear to be significant factors of prognosis.

  © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Antitumor activity of chLpMab-2, a human-mouse chimeric cancer-specific antihuman podoplanin antibody, via antibody-dependent cellular cytotoxicity. M.K. Kaneko, S. Yamada, T. Nakamura, et al. 2017;6(4):768-777. PubMed · Publisher · Free full text

  Abstract

  Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology. In this study we developed chLpMab-2, a human-mouse chimeric anti-hPDPN antibody, derived from LpMab-2. chLpMab-2 was produced using fucosyltransferase 8-knockout (KO) Chinese hamster ovary (CHO)-S cell lines. By flow cytometry, chLpMab-2 reacted with hPDPN-expressing cancer cell lines including glioblastomas, mesotheliomas, and lung cancers. However, it showed low reaction with normal cell lines such as lymphatic endothelial and renal epithelial cells. Moreover, chLpMab-2 exhibited high antibody-dependent cellular cytotoxicity (ADCC) against PDPN-expressing cells, despite its low complement-dependent cytotoxicity. Furthermore, treatment with chLpMab-2 abolished tumor growth in xenograft models of CHO/hPDPN, indicating that chLpMab-2 suppressed tumor development via ADCC. In conclusion, chLpMab-2 could be useful as a novel antibody-based therapy against hPDPN-expressing tumors.

  © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. M. Yamaji, A. Ota, M. Wahiduzzaman, et al. 2017;6(11):2646-2659. PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma (MPM), an asbestos-related occupational disease, is an aggressive and incurable tumor of the thoracic cavity. Despite recent advances in MPM treatment, overall survival of patients with MPM is very low. Recent studies have implicated that PI3K/Akt signaling is involved in MPM cell survival and development. To investigate the effects of Akt inhibitors on MPM cell survival, we examined the effects of nine selective Akt inhibitors, namely, afuresertib, Akti-1/2, AZD5363, GSK690693, ipatasertib, MK-2206, perifosine, PHT-427, and TIC10, on six MPM cell lines, namely, ACC-MESO-4, Y-MESO-8A, MSTO-211H, NCI-H28, NCI-H290, and NCI-H2052, and a normal mesothelial cell line MeT-5A. Comparison of IC50 values of the Akt inhibitors showed that afuresertib, an ATP-competitive specific Akt inhibitor, exerted tumor-specific effects on MPM cells. Afuresertib significantly increased caspase-3 and caspase-7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Moreover, afuresertib strongly arrested the cell cycle in the G1 phase. Western blotting analysis showed that afuresertib increased the expression of p21WAF1/CIP1 and decreased the phosphorylation of Akt substrates, including GSK-3β and FOXO family proteins. These results suggest that afuresertib-induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Furthermore, afuresertib significantly enhanced cisplatin-induced cytotoxicity. Interestingly, results of gene set enrichment analysis showed that afuresertib modulated the expression E2F1 and MYC, which are associated with fibroblast core serum response. Together, these results suggest that afuresertib is a useful anticancer drug for treating patients with MPM.

  © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Prognostic and predictive role of [18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with unresectable malignant pleural mesothelioma (MPM) treated with up-front pemetrexed-based chemotherapy. P.A. Zucali, E. Lopci, G.L. Ceresoli, et al. 2017;6(10):2287-2296. PubMed · Publisher · Free full text

  Abstract

  The aim of this study was to evaluate the role of metabolic parameters analyzed at baseline and at interim FDG-PET in predicting disease outcome in unresectable MPM patients receiving pemetrexed-based chemotherapy. A consecutive series of MPM patients treated between February 2004 and July 2013 with first-line pemetrexed-based chemotherapy, and evaluated by FDG-PET and CT scan at baseline and after two cycles of chemotherapy, was reviewed. Best CT scan response was assessed according to modified RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were correlated with FDG-PET parameters, such as maximum standardized uptake value (SUVmax ), total lesion glycolysis (TLG), and percentage changes in SUVmax (∆SUV) and TLG (∆TLG). Overall, 142 patients were enrolled; 77 (54%) received talc pleurodesis before chemotherapy. Baseline SUVmax and TLG showed a statistically significant correlation with PFS and OS (P < 0.05) in both group of patients (treated and untreated with pleurodesis). In 65 patients not receiving pleurodesis, SUVmax reduction ≥25% (∆SUV ≥ 25%) and TLG reduction ≥30% (∆TLG ≥ 30%) were significantly associated with longer PFS (P < 0.05). Patients showing both ∆SUV ≥ 25% and ∆TLG ≥ 30% responses had a significant reduction in the risk of disease progression (HR:0.31, P < 0.001) and death (HR:0.52, P = 0.044). Neither ∆SUV nor ∆TLG showed similar association with survival outcomes in patients treated with pleurodesis. Our study confirmed the prognostic role of baseline FDG-PET in a large series of MPM patients treated with first-line pemetrexed-based chemotherapy. Moreover, use of ∆SUV ≥ 25% and ∆TLG ≥ 30% as cut-off values to define early metabolic response supported the role of FDG-PET in predicting disease outcome and treatment response in patients not receiving pleurodesis.

  © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database. A. Farioli, M. Ottone, A.G. Morganti, et al. 2016;5(5):950-9. PubMed · Publisher · Free full text

  Abstract

  We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5 years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973-2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01-1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies ≥10 years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40 years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.

  © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Updated mortality study of a cohort of asbestos textile workers. E. Pira, C. Romano, F.S. Violante, et al. 2016;5(9):2623-8. PubMed · Publisher · Free full text

  Abstract

  Limited information is available on risk of peritoneal mesothelioma after asbestos exposure, and in general on the risk of cancer after cessation of asbestos exposure. We updated to 2013 the follow-up of a cohort of 1083 female and 894 male textile workers with heavy asbestos exposure (up to 100 fb/mL), often for short periods. A total of 1019 deaths were observed, corresponding to a standardized mortality ratio (SMR) of 1.68 (95% confidence interval [CI]: 1.57-1.78). SMRs were 29.1 (95% CI: 21.5-38.6) for peritoneal cancer, 2.96 (95% CI: 2.50-3.49) for lung cancer, 33.7 (95% CI: 25.7-43.4) for pleural cancer, and 3.03 (95% CI: 1.69-4.99) for ovarian cancer. For pleural and peritoneal cancer, there was no consistent pattern of risk in relation to time since last exposure, whereas for lung cancer there was an indication of a decline in risk after 25 years since last exposure. The findings of this unique cohort provide novel data for peritoneal cancer, indicating that - as for pleural cancer - the excess risk does not decline up to several decades after cessation of exposure.

  © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma. S. Nishikawa, A. Tanaka, A. Matsuda, et al. 2014;3(2):416-25. PubMed · Publisher · Free full text

  Abstract

  Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G1 /G1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.

  © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma. T. Sato, Y. Suzuki, T. Mori, et al. 2014;3(5):1377-84. PubMed · Publisher · Free full text

  Abstract

  Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to asbestos. The prognosis of mesothelioma remains disappointing despite multimodal treatment. We reported previously that N-ERC/mesothelin could be a useful biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme-linked immunosorbent assay (ELISA) system for its detection. However, the reproducibility of our previous 7-16 ELISA system has been revealed to be unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7-20 ELISA system. The subjects of this study were patients who were referred to our department with suspected pleural mesothelioma. The current study demonstrated that the newly established 7-20 ELISA system improved the sensitivity and specificity for diagnosing pleural mesothelioma compared with the previous system. Moreover, the 7-20 ELISA system showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum. Particularly for the epithelioid type, the area under the curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma. In conclusion, assessment of N-ERC/mesothelin with our newly established 7-20 ELISA system is clinically useful for the precise diagnosis of pleural mesothelioma.

  © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

• A contemporary analysis of morbidity and outcomes in cytoreduction/hyperthermic intraperitoneal chemoperfusion. M. Haslinger, V. Francescutti, K. Attwood, et al. 2013;2(3):334-42. PubMed · Publisher · Free full text

  Abstract

  The risks and benefits of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CS/HIPEC) continue to be debated by the oncology community. A retrospective analysis of contemporary data (2003-2011) was performed to provide objective information regarding surgical morbidity, mortality, and survival for patients undergoing CS/HIPEC at a comprehensive cancer center. While procedure-associated morbidity was comparable to other major surgical oncology procedures, there was no operative or 30-day mortality and 60-day mortality was 2.7%. Increasing numbers of bowel resections were found to correlate to an increased incidence of deep surgical site infections (including abscess and enterocutaneous fistula) and need for reoperation which was in turn associated with a decreased overall survival (OS) and progression-free survival (PFS). Five-year OS rates varied by site of tumor origin and histology (disseminated peritoneal adenomucinosis [91.3%], Mesothelioma [80.8%], Appendiceal Adenocarcinoma [38.7%], and Colorectal Adenocarcinoma [38.2%]). With an acceptable morbidity and mortality rate, CS/HIPEC should be included as an effective treatment modality in the multidisciplinary care of select patients with peritoneal metastases.

• Occupational dust exposure and head and neck squamous cell carcinoma risk in a population-based case-control study conducted in the greater Boston area. S.M. Langevin, M.D. McClean, D.S. Michaud, et al. 2013;2(6):978-86. PubMed · Publisher · Free full text

  Abstract

  Head and neck cancers account for an estimated 549,000 global cancer diagnoses each year. While tobacco use, alcohol consumption, and HPV16 infection are considered to be the major risk factors for this disease, occupational risk factors, including exposure to asbestos, have also been described, although dust exposures other than asbestos have been historically understudied. We have investigated the relationship between occupational exposures to five types of dusts, including sawdust, concrete dust, leather dust, metal dust, and chimney soot, and head and neck squamous cell carcinomas (HNSCC) in the greater Boston area. We report findings from a population-based case-control study involving 951 incident HNSCC cases and 1193 controls, frequency matched on age (±3 years), sex, and town/neighborhood of residence. Multivariable logistic regression was used to assess the association between occupational exposure to each type of dust and HNSCC, overall and by primary tumor site. After adjusting for age, sex, race, smoking, alcohol consumption, education, and HPV16 serology, laryngeal carcinoma risk increased for each decade of occupational exposure to sawdust (OR = 1.2, 95% CI: 1.0, 1.3) and metal dust (OR = 1.2, 95% CI: 1.0, 1.4); and HNSCC risk increased for each decade of occupational leather dust exposure (OR = 1.5, 95% CI: 1.2, 1.9). We have provided evidence for an association between occupational sawdust and metal dust and laryngeal squamous cell carcinoma, and leather dust and HNSCC, with increasing risk with longer duration at the exposed occupation.

  © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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