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41.
Real-world data on detection of germline and somatic pathogenic/likely pathogenic variants in BRCA1/2 and other susceptibility genes in ovarian cancer patients using next generation sequencing
Vida Stegel, Ana Blatnik, Erik Škof, Vita Šetrajčič Dragoš, Mateja Krajc, Brigita Gregorčič, Petra Škerl, Ksenija Strojnik, Gašper Klančar, Marta Banjac, Janez Žgajnar, Maja Ravnik-Oblak, Srdjan Novaković, 2022, original scientific article

Abstract: Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients.
Keywords: BRCA, ovarian cancer, tumor genotyping, HBOC
Published in DiRROS: 06.09.2022; Views: 536; Downloads: 284
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42.
Cancer patients’ survival according to socioeconomic environment in a high-income country with universal health coverage
Vesna Zadnik, Tina Žagar, Sonja Tomšič, Ana Mihor, Katarina Lokar, 2022, original scientific article

Abstract: Despite having an established systematic approach to population survival estimation in Slovenia, the influence of socioeconomic environment on cancer patients’ survival has not yet been evaluated. Thus, the main aim of our study was to quantify the potential impact of socioeconomic environment on cancer patients’ survival in our population in the 21st century. The net survival was calculated and stratified into quintiles of Slovenian version of the European Deprivation Index for all adult cancer patients diagnosed between 2004 and 2018 using the national cancer registry data. After accounting for basic demographic variables (age and gender), differences in stage at diagnosis, as well as the impact of the cancer treatment improvements over time, we found that cancer patients in Slovenia with lower socioeconomic status experience worse survival and have higher mortality. In particular, the odds of dying from oral, stomach, colorectal, liver, pancreatic, lung, breast, ovarian, corpus uteri, prostate, and bladder cancers, as well as for melanoma, leukemia, and non-Hodgkin lymphoma, are significantly higher in the socioeconomically most deprived group of patients compared to the most affluent group. The inequalities in cancer burden we found could help decision-makers to better understand the magnitude of this problem.
Keywords: cancer, population-survival, socioeconomic deprivation, cancer registry
Published in DiRROS: 06.09.2022; Views: 450; Downloads: 252
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44.
Solid cancer patients achieve adequate immunogenicity and low rate of severe adverse events after SARS-CoV-2 vaccination
Urška Janžič, Urška Bidovec, Katja Mohorčič, Loredana Mrak, Nina Fokter Dovnik, Marija Ivanović, Maja Ravnik, Marina Čakš, Erik Škof, Jerneja Debeljak, Peter Korošec, Matija Rijavec, 2022, original scientific article

Abstract: Background: SARS-CoV-2 vaccination in cancer patients is crucial to prevent severe COVID-19 disease course. Methods: This study assessed immunogenicity of cancer patients on active treatment receiving mRNA-based SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum, before, after the first and second doses and 3 months after a complete primary course of vaccination. Results were compared with healthy controls. Results: Of 112 patients, the seroconversion rate was 96%. A significant reduction in antibody levels was observed 3 months after vaccination in patients receiving immune checkpoint inhibitors versus control participants (p < 0.001). Adverse events were mostly mild. Conclusion: Immunogenicity after mRNA-based vaccine in cancer patients is adequate but influenced by the type of anticancer therapy. Antibody levels decline after 3 months, and thus a third vaccination is warranted.
Keywords: onkološko zdravljenje, imunogenost, osnovno cepljenje mRNA, čvrsti tumorji, anticancer treatment, immunogenicity, mRNA-based vaccination, solid cancer
Published in DiRROS: 24.06.2022; Views: 821; Downloads: 337
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45.
Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform
Marie Morfouace, Silvia Novello, A. Stevovic, C. Dooms, Urška Janžič, Thierry Berghmans, Rafal Dziadziuszko, T. Gorlia, Enriqueta Felip, Benjamin Besse, 2022, original scientific article

Abstract: Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients' molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency.
Keywords: thoracic neoplasms -- Europe, lung neoplasms -- Europe, diagnostic screening programs -- Europe, malignancies, lung cancer
Published in DiRROS: 24.06.2022; Views: 725; Downloads: 497
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46.
Carboxypeptidase cathepsin X defines a multifunctional role of gamma-enolase in cancer
Tjaša Vižin, Anja Pišlar, Ib Jarle Christensen, Hans Jørgen Nielsen, Pika Meško-Brguljan, Janko Kos, 2022, original scientific article

Abstract: Gamma-enolase enzymatic activity is involved in glycolysis, a prevalent process in cancer cell metabolism. Additionally, gamma-enolase has a pro-survival function, exhibited through the active site at the C-terminal end of the molecule. This activity is regulated by cysteine peptidase cathepsin X, which cleaves two amino acids at C-terminal end of gamma-enolase. In clinical practice, the determination of gamma-enolase as a tumour marker does not differ between total, uncleaved and C-terminally cleaved forms. However, levels of uncleaved gamma-enolase alone may provide additional clinical information. In this study we analysed cathepsin X, C- terminally uncleaved and total gamma-enolase in tumour cell lines and sera from 255 patients with colorectal cancer (CRC) by western blot, immunoprecipitation, enzymatic activity, ELISAs and ECLIA. Results show that uncleaved gamma-enolase, rather than total gamma- enolase, exhibits different levels in cells, being the highest in those, derived from metastatic sites or highly invasive tumours. Gamma-enolase is secreted into the extracellular space predominantly as an uncleaved form and levels were congruent to those within the cells. Furthermore, levels of uncleaved gamma-enolase in cells are inversely related to cathepsin X protein level and its enzymatic activity. Uncleaved gamma-enolase is also predominant form in sera of patients with CRC. Both forms exhibit similar stage dependent distribution, with slightly elevated levels in stage IV patients. Higher levels of total gamma-enolase are significantly related to shorter survival in patients with metastatic CRC. Results support evidence of additional pro-survival function of gamma-enolase in cancer. Future studies should focus on analysis of uncleaved gamma-enolase in tumour samples, which may provide additional relations to clinical indicators of disease progression.
Keywords: cancer, cathepsin X, cell survival, gamma-enolase, prognosis
Published in DiRROS: 06.04.2022; Views: 821; Downloads: 465
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47.
COVID-19 pandemic impact on cytopathology practice in the post-lockdown period : an international, multicenter study
Elena Vigliar, Pasquale Pisapia, Filippo Dello Iacovo, Izidor Kern, William C. Faquin, Martha Bishop Pitman, 2022, original scientific article

Abstract: Background. In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 “lockdown” period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). Methods. Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results. A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions. The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.
Keywords: covid-19, neoplasms, early detection of cancer, lung -- pathology -- cytology, diagnostic screening programs, fine-needle biopsy, cytopathology, fine-needle aspiration, malignancy rate
Published in DiRROS: 07.02.2022; Views: 804; Downloads: 255
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48.
Treatment patterns, testing practices, and outcomes in the pre-FLAURA era for patients with EGFR mutation-positive advanced NSCLC : a retrospective chart review (REFLECT)
Alfredo Addeo, Maximilian J Hochmair, Urška Janžič, Elizabeth Dudnik, Andriani Charpidou, Adam Płużański, Tudor Ciuleanu, Ivan Shterev Donev, Judith Elbaz, Jørgen Aarøe, René Ott, Nir Peled, 2021, original scientific article

Abstract: Background. Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). Here, we present the first results of a real-world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country. Materials and methods. Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first-line pembrolizumab (26 patients) or second-line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively. Results. Included patients had a median age of 64 years, most were male (55%), 6% were in performance status >/=2, and 18% had controlled central nervous system metastases at baseline. In first-line, the median progression-free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1-year overall survival (OS) was 62%. In second-line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1-year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3-4) in 12% of patients. Conclusion. The first real-world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real-world series, mainly coming from North America and Western European countries. Further data to inform on the real-world effectiveness of immunotherapy worldwide are needed.
Keywords: non-small cell lung carcinoma, immunotherapy, advanced non-small cell lung cancer, real-world data, Europe, Central Europe, Eastern Europe
Published in DiRROS: 15.12.2021; Views: 827; Downloads: 430
URL Link to file

49.
50.
Immunotherapy for metastatic non-small cell lung cancer : real-world data from an academic Central and Eastern European center
Marija Ivanović, Lea Knez, Ana Herzog, Mile Kovačević, Tanja Čufer, 2021, original scientific article

Abstract: Background. Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). Here, we present the first results of a real-world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country. Materials and methods. Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first-line pembrolizumab (26 patients) or second-line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively. Results. Included patients had a median age of 64 years, most were male (55%), 6% were in performance status >/=2, and 18% had controlled central nervous system metastases at baseline. In first-line, the median progression-free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1-year overall survival (OS) was 62%. In second-line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1-year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3-4) in 12% of patients. Conclusion. The first real-world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real-world series, mainly coming from North America and Western European countries. Further data to inform on the real-world effectiveness of immunotherapy worldwide are needed.
Keywords: non-small cell lung carcinoma, immunotherapy, advanced non-small cell lung cancer, real-world data, Central Europe, Europe, Eastern Europe
Published in DiRROS: 12.10.2021; Views: 947; Downloads: 287
URL Link to file

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