31. Non-small cell lung cancer in countries of Central and Southeastern Europe : diagnostic procedures and treatment reimbursement surveyed by the Central European Cooperative Oncology GroupAles Ryška, Rares Buiga, Albena Fakirova, Izidor Kern, Włodzimierz Olszewski, Lukas Plank, Sven Seiwerth, Erika Toth, Eri Zivka, Christiane Thallinger, Christoph Zielinski, Luka Brčić, 2018, original scientific article Abstract: This article analyzes the availability of different diagnostic procedures of non-small cell lung cancer (NSCLC) and the reimbursement landscape of drugs for NSCLC in countries of central and southeastern Europe (CEE). A survey was conducted by the Central European Cooperative Oncology Group. Results of the survey show that both availability and reimbursement of diagnoses of molecular alterations in NSCLC, the detection of which is essential for therapeutic decisions, varies widely between countries of CEE. Not only is "reflex" testing often substituted by analyses performed only "on demand," but reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. It was concluded that a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. Implications for Practice. This article provides an overview of the limitations in lung cancer treatment in countries of central and southeastern Europe, as well as the reimbursement status of various lung cancer treatment regimens in these countries, which directly impacts treatment options.
Keywords: Non-small cell lung carcinoma -- diagnosis -- economics -- Europe, molecular diagnostic techniques, precision medicine, Central Europe, Southeastern Europe, reimbursement
Published in DiRROS: 09.11.2020; Views: 1454; Downloads: 344
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32. Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapyMartina Vrankar, Izidor Kern, Karmen Stanič, 2020, original scientific article Abstract: Background: Expression of PD-L1 is the most investigated predictor of benefit from immune checkpoint blockade in advanced NSCLC but little is known about the association of PD-L1 expression and clinicopathological parameters of patients with unresectable stage III NSCLC. Methods: National registry data was searched for medical records of consecutive inoperable stage III NSCLC patients treated with ChT and RT from January 2012 to December 2017. Totally 249 patients were identified that met inclusion criteria and of those 117 patients had sufficient tissue for PD-L1 immunohistochemical staining. Results: Eighty patients (68.4%) expressed PD-L1 of >- 1% and 29.9% of more than 50%. Median PFS was 15.9 months in PD-L1 negative patients and 16.1 months in patients with PD-L1 expression >- 1% (p = 0.696). Median OS in PD-L1 negative patients was 29.9 months compared to 28.5 months in patients with PD-L1 expression >- (p = 0.888). There was no difference in median OS in patients with high PD-L1 expression (>- 50%) with 29.8 months compared to 29.9 months in those with low (1-49%) or no PD-L1 expression (p = 0.694). We found that patients who received a total dose of 60 Gy or more had significantly better median OS (32 months vs. 17.5 months, p < 0.001) as well as patients with PS 0 (33.2 vs. 20.3 months, p = 0.005). Conclusions: In our patients PD-L1 expression had no prognostic value regarding PFS and OS. Patients with good performance status and those who received a total radiation dose of more than 60 Gy had significantly better mOS.
Keywords: non small cell lung cancer, chemoradiotherapy, stage III
Published in DiRROS: 09.11.2020; Views: 1419; Downloads: 1013
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33. Global impact of the COVID-19 pandemic on cytopathology practice : results from an international survey of laboratories in 23 countriesElena Vigliar, Rima Cepurnaite, Eduardo Alcaraz-Mateos, Syed Z. Ali, Zubair W. Baloch, Claudio Bellevicine, Massimo Bongiovanni, Pavlina Botsun, Dario Bruzzese, Lukas Bubendorf, Izidor Kern, 2020, original scientific article Abstract: Background: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. Methods: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. Results: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). Conclusions: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.
Keywords: pathology, neoplasms, COVID-19, coronavirus disease 2019, fine-needle aspiration, malignancy rate
Published in DiRROS: 09.11.2020; Views: 3127; Downloads: 1391
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34. CD3+CD4-CD8- mucosal T cells are associated with uncontrolled chronic rhinosinusitis with nasal polypsTanja Soklič, Mira Šilar, Matija Rijavec, Ana Koren, Izidor Kern, Irena Hočevar-Boltežar, Peter Korošec, 2019, short scientific article Abstract: Increased mucosal double-negative (DN) CD3+CD4-CD8- T cells were found for the first time in CRS and were much more abundant in uncontrolled CRSwNP than in well-controlled CRSwNP.
Keywords: chronic rhinosinusitis, CD3+ T-cells, CD4- T-cells, CD8- T-cells
Published in DiRROS: 22.10.2020; Views: 1561; Downloads: 502
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35. Transcription factors gene expression in chronic rhinosinusitis with and without nasal polypsTanja Soklič, Matija Rijavec, Mira Šilar, Ana Koren, Izidor Kern, Irena Hočevar-Boltežar, Peter Korošec, 2019, original scientific article Abstract: Background. Chronic rhinosinusitis (CRS) current therapeutic approaches still fail in some patients with severe persistent symptoms and recurrences after surgery. We aimed to evaluate the master transcription factors gene expression levels of T cell subtypes in chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) that could represent new, up-stream targets for topical DNAzyme treatment. Patients and methods. Twenty-two newly diagnosed CRS patients (14 CRSwNP and 8 CRSsNP) were prospectively biopsied and examined histopathologically. Gene expression levels of T-box transcription factor (T-bet, TBX21), GATA binding protein 3 (GATA3), Retinoic acid-related orphan receptor C (RORC) and Forkhead box P3 (FOXP3) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Results. Eosinophilic CRSwNP was characterized by higher level of GATA3 gene expression compared to noneosinophilic CRSwNP, whereas there was no difference in T-bet, RORC and FOXP3 between eosinophilic and noneosinophilic CRSwNP. In CRSsNP, we found simultaneous upregulation of T-bet, GATA3 and RORC gene expression levels in comparison to CRSwNP; meanwhile, there was no difference in FOXP3 gene expression between CRSwNP and CRSsNP. Conclusions. In eosinophilic CRSwNP, we confirmed the type 2 inflammation by elevated GATA3 gene expression level. In CRSsNP, we unexpectedly found simultaneous upregulation of T-bet and GATA3 that is currently unexplained; however, it might originate from activated CD8+ cells, abundant in nasal mucosa of CRSsNP patients. The elevated RORC in CRSsNP could be part of homeostatic nasal immune response that might be better preserved in CRSsNP patients compared to CRSwNP patients. Further data on transcription factors expression rates in CRS phenotypes are needed.
Keywords: sinusitis, nasal polyps, Th1 cells, Th2 cells, Th17 cells, transcription factors, chronic rhinosinusitis
Published in DiRROS: 09.10.2020; Views: 1477; Downloads: 817
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36. Expression of FGFR1-4 in malignant pleural mesothelioma tissue and corresponding cell lines and its relationship to patient survival and FGFR inhibitor sensitivityGregor Vlačić, Mir Alireza Hoda, Thomas Klikovits, Katharina Sinn, Elisabeth Gschwandtner, Katja Mohorčič, Karin Schelch, Christine Pirker, Barbara Peter-Vörösmarty, Jelena Brankovic, Tanja Čufer, Aleš Rozman, Izidor Kern, 2019, original scientific article Abstract: Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not suffcient to predict FGFR inhibitor response in MPM cell lines.
Keywords: malignant pleural mesothelioma, fibroblast growth factor receptors, azbestos, immunotherapy, chemotherapy, genomic analysis, infigratinib
Published in DiRROS: 07.10.2020; Views: 12095; Downloads: 1012
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37. Idiopathic pulmonary fibrosis in patients with early-stage non-small-cell lung cancer after surgical resectionNežka Hribernik, Igor Požek, Izidor Kern, 2019, original scientific article Abstract: Background. The outcomes of patients with both lung cancer and idiopathic pulmonary fibrosis (IPF) are unfavorable. Therapeutic interventions for lung cancer such as surgery can cause acute exacerbation of IPF (aeIPF). This study aimed to assess the frequency of IPF in a group of patients with early-stage non-small-cell lung cancer (NSCLC) and to report clinical characteristics and outcomes of this cohort of patients. Patients and methods. This observational cohort retrospective study analyzed 641 pathological records of patients after surgical resection of early-stage non-small-cell lung cancer (NSCLC) at University Clinic Golnik from May 2010 to April 2017. Pathological records of NSCLC with coexisting IPF were reviewed. CT scans and biopsy specimens for this group of patients were analyzed by a thoracic radiologist and pathologist, independently. We searched radiological and pathological features of usual interstitial pneumonia (UIP) pattern in this group of patients. We report the clinical characteristics and outcome of this cohort of patients. Results. Out of 641 patients with early-stage NSCLC, only 13 (2.0%) had histologically and radiologically proven coexisting UIP/IPF. Squamous cell carcinoma was the most common type of lung cancer (7/13 patients). The majority of tumors were small size (all being pT1 or pT2), stage I–II (11/13 patients), located in the lower lung lobes (11/13 patients). Almost all patients were current or ex-smokers (11/13 patients). There were two pathologically confirmed fatal cases (15.4%) due to aeIPF in the first two months after radical treatment, one after adjuvant radiotherapy and the other after surgery. Out of 13 patients, one patient had a lung cancer relapse. Conclusions. Frequency of UIP/IPF in surgically treated early stage NSCLC is rather low. Our observational study shows that radical treatment of lung cancer can cause aeIPF with dismal outcome in this group of patients. The standard of care in these mostly elderly patients still remains unresolved.
Keywords: non-small-cell lung cancer, early-stage cancer, idiopathic pulmonary fibrosis, surgery, radiotherapy
Published in DiRROS: 07.10.2020; Views: 1927; Downloads: 857
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38. Multicenter evaluation of the fully automated PCR-based Idylla EGFR Mutation Assay on formalin-fixed, paraffin-embedded Q1 tissue of human lung cancerSolène M. Evrard, Estelle T. Clermont, Isabelle Rouquette, Samuel Murray, Sebastian Dintner, Yun-Chung Nam-Apostolopoulos, Beatriz Bellosillo, Mar V. Rodriguez, Ernest Nadal, Klaus H. Wiedorn, Mitja Rot, Izidor Kern, 2019, original scientific article Abstract: Before initiating treatment of advanced nonesmall-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15- center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from nonesmall-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm2 of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure.
Keywords: non-small cell lung carconima -- diagnosis -- genetics, ErbB receptors, sequence analysis, tyrosine kinase inhibitors, epidermal growth factor receptor
Published in DiRROS: 07.10.2020; Views: 1363; Downloads: 968
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39. Priporočila za obravnavo bolnikov s pljučnim rakomMartina Vrankar, Nina Boc, Izidor Kern, Aleš Rozman, Karmen Stanič, Tomaž Štupnik, Mojca Unk, Maja Ebert Moltara, Vesna Zadnik, Katja Adamič, Jernej Benedik, Marko Bitenc, Jasna But-Hadžić, Anton Crnjac, Eva Ćirić, Tanja Čufer, Goran Gačevski, Marta Globočnik Kukovica, Kristina Gornik-Kramberger, Maja Ivanetič Pantar, Staša Jelerčič, Veronika Kloboves-Prevodnik, Mile Kovačević, Luka Ležaič, Mateja Marc-Malovrh, Katja Mohorčič, Bogdan Vidmar, Dušanka Vidovič, Gregor Vlačić, Ana Lina Vodušek, Rok Zbačnik, Ivana Žagar, 2020, professional article Keywords: pljučni rak, priporočila
Published in DiRROS: 22.09.2020; Views: 1873; Downloads: 705
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40. Lung cancer biomarker testing : perspective from EuropeErik Thunnissen, Birgit Weynand, Dalma Udovicic-Gagula, Luka Brčić, Malgorzata Szolkowska, Paul Hofman, Silvana Smojver-Ježek, Sisko Anttila, Fiorella Calabrese, Izidor Kern, 2020, review article Abstract: A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future.
Keywords: lung neoplasms -- diagnosis -- therapy -- Europe, lung cancer, predictive testing
Published in DiRROS: 21.09.2020; Views: 1613; Downloads: 1047
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