Radiology and Oncology

Our medical research library holds 19 studies published in Radiology and Oncology (2010–2026). 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. 19 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Sciendo
• Published: 1992 to the present, Poland
• Language: English
• ISSN: 1318-2099 (print), 1581-3207 (electronic)
• Continues: Radiologia Iugoslavica
• Its record in the NLM Catalog

2020s

• Genetic variability of immune checkpoints in asbestos-related diseases. I. Zeljkovic, K. Goricar, T. Blagus, et al. 2026;60(2):271-281. PubMed · Publisher · Free full text

  Abstract

  Background: Asbestos exposure is associated with asbestos-related diseases such as pleural plaques, asbestosis, lung cancer, malignant mesothelioma (MM), as well as several other types of cancer. Although the exact mechanism underlying the development of asbestos-related diseases is not yet fully understood, the immune system may play an important role. Immune checkpoints such as programmed cell death receptor 1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) regulate immune responses and are crucial for maintaining immune tolerance, while defects in these mechanisms can lead to the development of cancer. The aim of present study was to investigate the association of polymorphisms in the immune checkpoint genes for PD-1 (PDCD1), PD-L1 (CD274), and CTLA-4 (CTLA4) with the risk of asbestos-related diseases.

  Subjects And Methods: We conducted a retrospective case-control study. The cases included individuals with asbestosis or pleural plaques and MM patients. The controls were asbestos-exposed subjects who did not develop asbestos-related diseases. All subjects were genotyped for PDCD1 (rs2227982, rs222798, rs10204525), CD274 (rs2297136, rs4143815, rs4742098) and CTLA4 (rs5742909, rs4553808, rs231775) polymorphisms using competitive allele-specific PCR. Statistical analysis was performed using logistic regression.

  Results: Our study showed that the CTLA4 rs4553808 polymorphism was associated with a decreased risk of asbestosrelated diseases (OR = 0.34, 95% CI = 0.15-0.74, P = 0.007). Homozygous carriers of polymorphic rs4553808 G allele had a lower risk of developing pleural plaques as well as MM compared to the control group (OR = 0.28, 95% CI = 0.11-0.68, P = 0.01, and OR = 0.38, 95% CI = 0.16 -0.93, P = 0.03, respectively). However, carriers of polymorphic CTLA4 rs231775 GG genotype had a higher risk of developing MM compared to the group of subjects with pleural plaques (OR = 1.79, 95% CI = 1.10-2.89, P = 0.02). The other investigated polymorphisms were not associated with any of the asbestos-related diseases.

  Conclusions: CTLA4 polymorphisms may play a role in the susceptibility for asbestos-related diseases. Our results may contribute to a better understanding of the pathogenesis and progression of asbestos-related diseases.

  © 2026 Irma Zeljkovic et al.

• Assessing the impact of waste co-incineration at the Anhovo cement plant (Slovenia) on the regional cancer burden. V. Zadnik, M. Birk, T. Oblak, et al. 2025;59(3):412-424. PubMed · Publisher · Free full text

  Abstract

  Background: This epidemiological study aims to assess the cancer risk potentially associated with environmental exposure resulting from cement production and waste co-incineration at the Anhovo cement plant in Western Slovenia and to develop a strong and reliable methodological framework for the long-term surveillance of environmentally related cancer risks in small geographical areas.

  Materials And Methods: We integrated all the available data sources: cancer cases from the population-based Slovenian Cancer Registry; background population; and available measurements on exposure to air PM10 particles and chromium (Cr) in the soil in the municipality of Kanal and the wider Goriška region. Relative risks of cancer in small geographical areas were estimated using Bayesian hierarchical spatial models and the population attributable fractions of the modelled risk factors were calculated. The point source analysis compared the cancer risk near the cement plant to that in more distant areas.

  Results: The analysis did not reveal any excess cancer incidence in the area of the Anhovo cement plant or an association with the PM10 particles and Cr in the soil. The incidence of mesothelioma remains high in the region, but stable in the last two decades.

  Conclusions: In view of the environmental pollution caused by either historical cement production or the potential impact of current waste co-incineration activities in Kanal, we strongly recommend that a follow-up epidemiological study be carried out in the next 10 to 20 years. The methodological framework established in the present study provides a foundation for the ongoing surveillance of the cancer burden in the region.

  © 2025 Vesna Zadnik et al., published by Sciendo.

• Fibulin-3 in plasma and pleural effusion as a biomarker of mesothelioma. K. Adamic, M.M. Malovrh, U.B. Stojkovic, et al. 2025;59(2):225-232. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a global health concern linked to asbestos exposure. In Slovenia, regions with high asbestos exposure rates make MPM a significant public health issue. Although thoracoscopic biopsy is the gold standard for MPM diagnosis, its invasiveness highlights the need for reliable, non-invasive diagnostic biomarkers.

  Patients And Methods: This prospective study evaluated the diagnostic potential of fibulin-3 as a biomarker for MPM, focusing on its ability to distinguish MPM from other pleural conditions, its association with disease stage and histological subtype, and its prognostic value for survival. Ninety patients, who underwent diagnostic thoracoscopic biopsy from January 2013 to October 2014, were included. Fibulin-3 levels in plasma and pleural effusion were measured using enzyme-linked immunosorbent assay (ELISA), and clinical data were analysed with statistical tests, including receiver operating characteristic (ROC) analysis.

  Results: The study cohort comprised 32 patients with MPM, 24 with metastatic pleural carcinoma, and 34 with benign pleural diseases. Plasma fibulin-3 levels were significantly elevated (p = 0.0132) in MPM patients compared to those with benign pleural effusions due to asbestos exposure, with a cut-off of 12.31 ng/mL showing 100% specificity but low sensitivity (39.39%). Elevated fibulin-3 levels in pleural effusion correlated with advanced disease (p = 0.0463) and aggressive histological subtypes (p = 0.0324). No significant survival correlation was observed.

  Conclusions: While plasma fibulin-3 is a highly specific biomarker for MPM, its low sensitivity limits its standalone diagnostic utility. Its potential role in risk stratification and early detection of MPM at-risk populations using combination of different and new biomarkers warrants further study.

  © 2025 Katja Adamic et al., published by Sciendo.

• Genetic variability of HIF1A and response to treatment with cisplatin in combination with pemetrexed or gemcitabine in patients with malignant mesothelioma. M. Setina, E. Setina, Z. Doljak, et al. 2025;59(3):403-411. PubMed · Publisher · Free full text

  Abstract

  Background: Treatment of malignant mesothelioma (MM) still relies on chemotherapy with cisplatin in combination with pemetrexed or other drugs. Studies indicate that hypoxic conditions within tumour tissue may reduce responsiveness to cisplatin-based chemotherapy. Hypoxia-inducible factors (HIF) play an important role in regulation of cellular adaptation to hypoxia. The aim of our study was to investigate single nucleotide polymorphisms (SNPs) in the HIF1A gene coding for the regulatory alpha subunit (HIF-1A) and their role in the response to chemotherapy in patients with MM.

  Patients And Methods: Our retrospective genetic association study included 234 patients with MM, who were treated with a combination of cisplatin/pemetrexed or cisplatin/gemcitabine at the Institute of Oncology Ljubljana between January 2001 and September 2018. Selected HIF1A SNPs (rs1154965, rs11549467, and rs2057482) were genotyped using the competitive allele-specific polymerase chain reaction (KASP). Additionally, we used a TaqMan assay for independent confirmation of rs11549465 genotyping results. The impact of the SNPs on response to chemotherapy was analysed using logistic regression. For survival analysis, we used the Kaplan-Meier method and Cox regression.

  Results: In heterozygotes with the HIF1A rs11549465 CT genotype, response to chemotherapy was significantly worse compared to homozygotes with the CC genotype, but only after adjustment for weight loss and CRP (ROadj = 0.37; 95% CI = 0.14-0.97; Padj = 0.044). HIF1A rs11549467 and rs2057482 were not associated with response to chemotherapy (all P > 0.05). None of the investigated SNPs were associated with progression-free survival or overall survival (all P > 0.05).

  Conclusions: Among the investigated HIF1A SNPs, only rs11549465 has showed association with a worse response to chemotherapy after the adjustment for clinical parameters. The findings of this study have improved our understanding of the role of HIF1A polymorphisms in MM and may offer valuable insights into their impact on other cancers as well.

  © 2025 Matic Setina et al., published by Sciendo.

• Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases. A. Mervic, K. Goricar, T. Blagus, et al. 2024;58(1):87-98. PubMed · Publisher · Free full text

  Abstract

  Background: Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).

  Subjects And Methods: We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.

  Results: Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).

  Conclusions: Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.

  © 2024 Ana Mervic et al., published by Sciendo.

• A review of tumor treating fields (TTFields): advancements in clinical applications and mechanistic insights. X. Li, K. Liu, L. Xing, et al. 2023;57(3):279-291. Review PubMed · Publisher · Free full text

  Abstract

  Background: Tumor Treating Fields (TTFields) is a non-invasive modality for cancer treatment that utilizes a specific sinusoidal electric field ranging from 100 kHz to 300 kHz, with an intensity of 1 V/cm to 3 V/cm. Its purpose is to inhibit cancer cell proliferation and induce cell death. Despite promising outcomes from clinical trials, TTFields have received FDA approval for the treatment of glioblastoma multiforme (GBM) and malignant pleural mesothelioma (MPM). Nevertheless, global acceptance of TTFields remains limited. To enhance its clinical application in other types of cancer and gain a better understanding of its mechanisms of action, this review aims to summarize the current research status by examining existing literature on TTFields' clinical trials and mechanism studies.

  Conclusions: Through this comprehensive review, we seek to stimulate novel ideas and provide physicians, patients, and researchers with a better comprehension of the development of TTFields and its potential applications in cancer treatment.

  © 2023 Xing Li et al., published by Sciendo.

• The association of genetic factors with serum calretinin levels in asbestos-related diseases. C. Zupanc, A. Franko, D. Strbac, et al. 2023;57(4):473-486. PubMed · Publisher · Free full text

  Abstract

  Background: Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.

  Subjects And Methods: The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis.

  Results: Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2 rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335 genotypes.

  Conclusions: The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.

  © 2023 Cita Zupanc et al., published by Sciendo.

• The role of polymorphisms in glutathione-related genes in asbestos-related diseases. A. Franko, K. Goricar, M. Dodic Fikfak, et al. 2021;55(2):179-186. PubMed · Publisher · Free full text

  Abstract

  Background: The study investigated the influence of GCLC, GCLM, GSTM1, GSTT1 and GSTP1 polymorphisms, as well as the influence of interactions between polymorphism and interactions between polymorphisms and asbestos exposure, on the risk of developing pleural plaques, asbestosis and malignant mesothelioma (MM).

  Subjects And Methods: The cross sectional study included 940 asbestos-exposed subjects, among them 390 subjects with pleural plaques, 147 subjects with asbestosis, 225 subjects with MM and 178 subjects with no asbestos-related disease. GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272 genotypes were determined using PCR based methods. In statistical analysis, logistic regression was used.

  Results: GSTT1 null genotype was associated with the decreased risk for pleural plaques (OR = 0.63; 95% CI = 0.40-0.98; p = 0.026) and asbestosis (OR = 0.51; 95% CI = 0.28-0.93; p = 0.028), but not for MM. A positive association was found between GSTP1 rs1695 AG + GG vs. AA genotypes for MM when compared to pleural plaques (OR = 1.39; 95% CI = 1.00-1.94; p = 0.049). The interactions between different polymorphisms showed no significant influence on the risk of investigated asbestos-related diseases. The interaction between GSTT1 null polymorphism and asbestos exposure decreased the MM risk (OR = 0.17; 95% CI = 0.03-0.85; p = 0.031).

  Conclusions: Our findings suggest that GSTT1 null genotype may be associated with a decreased risk for pleural plaques and asbestosis, may modify the association between asbestos exposure and MM and may consequently act protectively on MM risk. This study also revealed a protective effect of the interaction between GSTP1 rs1695 polymorphism and asbestos exposure on MM risk.

  © 2021 Alenka Franko, Katja Goricar, Metoda Dodic Fikfak, Viljem Kovac, Vita Dolzan, published by Sciendo.

• Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases. K. Goricar, V. Kovac, M. Dodic-Fikfak, et al. 2020;54(1):86-95. PubMed · Publisher · Free full text

  Abstract

  Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.

• The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma. P. Piber, N. Vavpetic, K. Goricar, et al. 2020;54(4):429-436. PubMed · Publisher · Free full text

  Abstract

  Background Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13-0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14-0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28-0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions Our findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.

2010s

• Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment. B. Senk, K. Goricar, V. Kovac, et al. 2019;53(1):96-104. PubMed · Publisher · Free full text

  Abstract

  Background Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment. Patients and methods The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis. Results AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37-0.96, Padj = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27-0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27-0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00-4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01-9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00-8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00-13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13-19.05, P = 0.034) in additive model. Conclusions AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.

• The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma. K. Levpuscek, K. Goricar, V. Kovac, et al. 2019;53(2):206-212. PubMed · Publisher · Free full text

  Abstract

  Background Malignant mesothelioma (MM) is a rare aggressive tumour of mesothelium caused by asbestos exposure. It has been suggested that the genetic variability of proteins involved in DNA repair mechanisms affects the risk of MM. This study investigated the influence of functional polymorphisms in ERCC1 and XRCC1 genes, the interactions between these polymorphisms as well as the interactions between these polymorphisms and asbestos exposure on MM risk. Patients and methods In total, 237 cases with MM and 193 controls with no asbestos-related disease were genotyped for ERCC1 and XRCC1 polymorphisms. Results ERCC1 rs3212986 polymorphism was significantly associated with a decreased risk of MM (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.41-0.91; p = 0.014). No associations were observed between other genetic polymorphisms and MM risk. Interactions between polymorphisms did not significantly influence MM risk. Interaction between ERCC1 rs11615 and asbestos exposure significantly influenced MM risk (OR = 3.61; 95% CI = 1.12-11.66; p = 0.032). Carriers of polymorphic ERCC1 rs11615 allele who were exposed to low level of asbestos had a decreased risk of MM (OR = 0.40; 95% CI = 0.19-0.84; p = 0.016). Interactions between other polymorphisms and asbestos exposure did not significantly influence MM risk. Conclusions Our findings suggest that the genetic variability of DNA repair mechanisms could contribute to the risk of developing MM.

• Matrix Metalloproteinases Polymorphisms as Baseline Risk Predictors in Malignant Pleural Mesothelioma. D. Strbac, K. Goricar, V. Dolzan, et al. 2018;52(2):160-166. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure.

  Patients And Methods: The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%-75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).

  Results: Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44-1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35-0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma.

  Conclusions: The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

• The Influence of Genetic Variability on the Risk of Developing Malignant Mesothelioma. A. Franko, N. Kotnik, K. Goricar, et al. 2018;52(1):105-111. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in the mechanism of carcinogenesis; therefore, genetic variability in antioxidative defence may modify an individual's susceptibility to this cancer. This study investigated the influence of functional polymorphisms of NQO1, CAT, SOD2 and hOGG1 genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk.

  Patients And Methods: In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms.

  Results: The risk of malignant mesothelioma increased with smoking, odds ratio (OR) 9.30 [95% confidence interval (CI): 4.83-17.98] and slightly with age, OR 1.10 (95% CI: 1.08-1.14). Medium and high asbestos exposures represented 7-times higher risk of malignant mesothelioma compared to low exposure, OR 7.05 (95% CI 3.59-13.83). NQO1 rs1800566 was significantly associated with increased malignant mesothelioma risk, OR 1.73 (95% CI 1.02-2.96). Although there was no independent association between either CAT rs1001179 or hOGG1 rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, ORint 0.27 (95% CI 0.10-0.77).

  Conclusions: Our findings suggest a role of both genetic variability in antioxidative defence and repair as well as the impact of gene-gene interactions in the development of malignant mesothelioma. The results of this study could add to our understanding of pathogenesis of malignant mesothelioma and contribute to prevention and earlier diagnosis of this aggressive cancer.

• Fibulin-3 as a biomarker of response to treatment in malignant mesothelioma. V. Kovac, M. Dodic-Fikfak, N. Arneric, et al. 2015;49(3):279-85. PubMed · Publisher · Free full text

  Abstract

  Background: Fibulin-3 is a new potential biomarker for malignant mesothelioma (MM). This study evaluated the potential applicability of fibulin-3 plasma levels as a biomarker of response to treatment and its prognostic value for progressive disease within 18 months. The potential applicability of fibulin-3 in comparison with or in addition to soluble mesothelin-related peptides (SMRP) was also assessed.

  Patients And Methods: The study included 78 MM patients treated at the Institute of Oncology Ljubljana between 2007 and 2011. Fibulin-3 levels in plasma samples obtained before treatment and in various responses to treatment were measured with the enzyme-linked immunosorbent assay.

  Results: In patients evaluated before the treatment, fibulin-3 levels were not influenced by histopathological sub-types, tumour stages or the presence of metastatic disease. Significantly higher fibulin-3 levels were found in progressive disease as compared to the levels before treatment (Mann-Whitney [U] test = 472.50, p = 0.003), in complete response to treatment (U = 42.00, p = 0.010), and in stable disease (U = 542.00, p = 0.001). Patients with fibulin-3 levels exceeding 34.25 ng/ml before treatment had more than four times higher probability for developing progressive disease within 18 months (odds ratio [OR] = 4.35, 95% confidence interval [CI] 1.56-12.13). Additionally, patients with fibulin-3 levels above 34.25 ng/ml after treatment with complete response or stable disease had increased odds for progressive disease within 18 months (OR = 6.94, 95% CI 0.99-48.55 and OR = 4.39, 95% CI 1.63-11.81, respectively).

  Conclusions: Our findings suggest that in addition to SMRP fibulin-3 could also be helpful in detecting the progression of MM.

• Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma. K. Goricar, V. Kovac, V. Dolzan. 2014;48(2):163-72. PubMed · Publisher · Free full text

  Abstract

  Introduction: A combination of pemetrexed and cisplatin has been shown to improve the outcome in patients with malignant pleural mesothelioma (MPM), however, there is a great heterogeneity in treatment response among patients. The aim of our study was to evaluate the influence of polymorphisms in folate pathway and transporter genes on pemetrexed treatment outcome in Slovenian patients with MPM.

  Methods: MPM patients treated with pemetrexed in the course of a prospective randomized clinical trial were genotyped for nineteen polymorphisms in five genes of folate pathway and six transporter genes. Logistic regression was used to assess the influence of polymorphisms on treatment efficacy and toxicity, while Cox regression was used to determine their influence on progression-free and overall survival.

  Results: Patients with at least one polymorphic MTHFD1 rs2236225 allele had a significantly lower response rate (p = 0.005; odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.03-0.54) and shorter progression-free survival (p = 0.032; hazard ratio [HR] = 3.10; 95% CI = 1.10-8.74) than non-carriers. Polymorphisms in transporter genes did not influence survival; however, several were associated with toxicity. Liver toxicity was significantly lower in carriers of polymorphic ABCC2 rs2273697 (p = 0.028; OR = 0.23; 95% CI = 0.06-0.85), SLCO1B1 rs4149056 (p = 0.028; OR = 0.23; 95% CI = 0.06-0.85) and rs11045879 (p = 0.014; OR = 0.18; 95% CI = 0.05-0.71) alleles compared to non-carriers, as well as in patients with SLCO1B1 GCAC haplotype (p = 0.048; OR = 0.17; 95% CI = 0.03-0.98). Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004; OR = 10.67; 95% CI = 2.15-52.85) and ABCC2 CAG haplotype (p = 0.006; OR = 5.67; 95% CI = 1.64-19.66).

  Conclusions: MTHFD1 polymorphism affected treatment response and survival, while polymorphisms in ABCC2 and SLCO1B1 transporter genes influenced the risk for toxicity. These polymorphisms could serve as potential markers of pemetrexed treatment outcome in patients with MPM.

• Semirigid thoracoscopy: an effective method for diagnosing pleural malignancies. A. Rozman, L. Camlek, I. Kern, et al. 2014;48(1):67-71. PubMed · Publisher · Free full text

  Abstract

  Background: Thoracoscopy with a semirigid instrument is a recent technique for diagnosing pleural diseases. The purpose of this study was to report diagnostic yield and complications of the method.

  Patients And Methods: Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry with a semirigid thoracoscope (Olympus LTF-160). Data were collected prospectively between 2008 and 2012.

  Results: One hundred fifteen thoracoscopies were performed on 111 patients. The median age was 65 years (range 28-86 years), 14.4% were female and 85.6% male. Seventy-three (65.8%) patients had malignant pleural disease (malignant mesothelioma, metastatic cancer) and 38 (34.2%) had benign disease. The sensitivity, negative predictive value, and accuracy of the procedure for malignancy were 96.0%, 93.0%, and 97.4% respectively. Pleurodesis was carried out in 34 patients; in 32 (94.1%) it was assessed as successful after 1 month. There were 24 adverse events: three empyemas/pleural infections, three bronchopleural fistulae after chest tube placement and lung re-expansion, five patients had excessive pain after pleurodesis, six patients had sedation-associated hypotension, and seven patients had self-limited fever after plerodesis. One patient died 11 days after a procedure for advanced carcinoma.

  Conclusions: Semirigid thoracoscopy is an accurate and safe method for evaluation of pleural diseases and useful for therapeutic talc pleurodesis.

• Improved survival after introduction of chemotherapy for malignant pleural mesothelioma in Slovenia: Population-based survey of 444 patients. V. Kovac, M. Zwitter, T. Zagar. 2012;46(2):136-44. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma is a rare tumour with increasing frequency throughout the world. Due to long latency after exposure to asbestos, restrictions in the production and use of asbestos have not yet alleviated the burden of mesothelioma. During the last decade, several trials confirmed the benefit of systemic treatment with drugs such as doublets with cisplatina and gemcitabine or pemetrexed for carefully selected patients in good performance status. The purpose of this survey was to assess the impact of systemic treatment for the whole national population of patients with mesothelioma. PATIENTS AND METHODS.: A retrospective study included all patients in Slovenia with histologically confirmed diagnosis of malignant pleural mesothelioma in the period from 1974 till 2008. Data from the Cancer Registry of Slovenia were supplemented by review of clinical records of the Institute of Oncology in Ljubljana where virtually all non-surgical treatment for mesothelioma was performed. We analysed the incidence, treatment, and survival of patients treated in the era of infrequent chemotherapy (1974-2003, the first period) and after it (2004-2008, the second period).

  Results: The survey included 444 patients, of whom 325 and 119 were diagnosed in the first and second period, respectively. Joinpoint regression analysis showed that after 1995 the trend in crude incidence rates increased more rapidly; the annual change was 0.03 per 100,000 per year before 1995 and 0.06 per 100,000 per year after. There was clear male predominance (70%) throughout the period covered by the survey. The proportion of patients above 65 years of age increased from 41.8% to 54.6% for the first and second period, respectively (p = 0.02). With a total of 52 (11.7%) operated patients, surgical treatment was rare and used only for selected patients with early disease and without comorbidity, leading to their relatively long median survival of 13.6 months. Chemotherapy was applied to 56 (17.2%) and to 96 (80.7%) patients during the first and second period, respectively. While a variety of older drugs were used in the first period, the most common regimen in the second period (applied to 91 patients) was doublet of low-dose gemcitabine in prolonged infusion and cisplatin. For the whole population of patients regardless the mode of treatment, median survival was 7.4 and 12.6 months (p-value = 0.037) for the first and second period, respectively.

  Conclusions: Increasing incidence, male predominance and increased proportion of older patients confirm that the burden of mesothelioma persists in spite of a 15-years old ban in the production of asbestos. Modern chemotherapy, and in particular treatment with low-dose gemcitabine in prolonged infusion and cisplatin significantly prolonged median survival of patients with malignant pleural mesothelioma in Slovenia.

• 3T MRI in evaluation of asbestos-related thoracic diseases - preliminary results. J. Podobnik, I. Kocijancic, V. Kovac, et al. 2010;44(2):92-6. PubMed · Publisher · Free full text

  Abstract

  Background: 3T high-field magnetic resonance imaging (MRI) scanners have recently become available for the clinical use and are being increasingly applied in the field of whole-body imaging and chest imaging as well. The aim of this study was to evaluate the diagnostic potential of 3 T MRI as a complementary imaging modality to CT in detecting the pathological changes of asbestos-related thoracic diseases.

  Patients And Methods: Fifteen patients with the asbestos-related thoracic disease were scheduled for 3T MRI. Five had a benign form of the disease and 10 had malignant pleural mesothelioma (MPM). From the patients with a benign form of the disease their last CT examination in digital form was acquired and patients with MPM were scheduled for CT examination with contrast media. The protocol of MR imaging consists of T2-weighted cardiac-gated breath-hold turbo spin echo (TSE) sequences in coronal, sagittal and axial plane and T1-weighted cardiac-gated breath-hold TSE black blood in axial plane. In T2-weighted sequences in axial plane, fat saturation was also used. CT examinations were obtained with the administration of the contrast medium from lung apices to the lower end of the liver. Images of 5 mm (mediastinum window) and 3 mm (lung window) in axial plan were reconstructed. MRI signal intensity of lesions and adjacent muscles on Syngo MultiModality Work Place were measured.

  Results: Compared to muscles pleural plaques appeared hypo-intense to iso-intense on T1 weighted images (in 100%) and also hypo-intense on T2 fs-weighted images (in 100%). MPM appeared inhomogeneous hypo-intense to iso-intense on T1-weighted and hyperintense on T2 fs-weighted images in all patients (100%).

  Conclusions: These preliminary results pointed out that MRI was equal or even better compared with CT examination for detecting possible malignant potential of pleural changes in the asbestos-related pleural disease, using signal intensity measurements of T2 fs-weighted images. The 3T MRI enabled the accurate determination of chest pathology and it could be used for imaging of patients with the asbestos-related thoracic disease. MRI is particularly valuable because a patient is not exposed to the harmful radiation which is important if imaging methods are used repeatedly, like in screening programs or in monitoring of treatment results. This finding turned us to propose 3T MRI imaging technique as a non-ionizing imaging method for the follow-up of patients with the isolated pleural form of the asbestos-related disease.

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