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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 Group
Ales Ryška, Rares Buiga, Albena Fakirova, Izidor Kern, Włodzimierz Olszewski, Lukas Plank, Sven Seiwerth, Erika Toth, Eri Zivka, Christiane Thallinger, Christoph Zielinski, Luka Brčić, 2018, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: Non-small cell lung carcinoma -- diagnosis -- economics -- Europe, molecular diagnostic techniques, precision medicine, Central Europe, Southeastern Europe, reimbursement
Objavljeno v DiRROS: 09.11.2020; Ogledov: 1467; Prenosov: 347
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32.
Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy
Martina Vrankar, Izidor Kern, Karmen Stanič, 2020, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: non small cell lung cancer, chemoradiotherapy, stage III
Objavljeno v DiRROS: 09.11.2020; Ogledov: 1430; Prenosov: 1020
.pdf Celotno besedilo (822,12 KB)
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33.
Idiopathic pulmonary fibrosis in patients with early-stage non-small-cell lung cancer after surgical resection
Nežka Hribernik, Igor Požek, Izidor Kern, 2019, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: non-small-cell lung cancer, early-stage cancer, idiopathic pulmonary fibrosis, surgery, radiotherapy
Objavljeno v DiRROS: 07.10.2020; Ogledov: 1938; Prenosov: 862
.pdf Celotno besedilo (969,72 KB)

34.
Multicenter evaluation of the fully automated PCR-based Idylla EGFR Mutation Assay on formalin-fixed, paraffin-embedded Q1 tissue of human lung cancer
Solène 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, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: non-small cell lung carconima -- diagnosis -- genetics, ErbB receptors, sequence analysis, tyrosine kinase inhibitors, epidermal growth factor receptor
Objavljeno v DiRROS: 07.10.2020; Ogledov: 1381; Prenosov: 980
.pdf Celotno besedilo (714,24 KB)
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36.
Lung cancer biomarker testing : perspective from Europe
Erik Thunnissen, Birgit Weynand, Dalma Udovicic-Gagula, Luka Brčić, Malgorzata Szolkowska, Paul Hofman, Silvana Smojver-Ježek, Sisko Anttila, Fiorella Calabrese, Izidor Kern, 2020, pregledni znanstveni članek

Povzetek: 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.
Ključne besede: lung neoplasms -- diagnosis -- therapy -- Europe, lung cancer, predictive testing
Objavljeno v DiRROS: 21.09.2020; Ogledov: 1637; Prenosov: 1057
.pdf Celotno besedilo (1,80 MB)
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37.
Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : updated analysis of the observational GioTag study
Maximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Lara Wang, Angela Märten, Tanja Čufer, 2019, izvirni znanstveni članek

Povzetek: Aims: Overall survival (OS) and updated time to treatment failure (TTF) analysis of patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer who received sequential afatinib/osimertinib in the real-world GioTag study. Patients & methods: Patients had T790M-positive disease following first-line afatinib and received osimertinib treatment (n = 203). Primary outcome was TTF. The OS analysis was exploratory. Results: Median OS was 41.3 months (90% CI: 36.8-46.3) overall and 45.7 months (90% CI: 45.3-51.5) in patients with Del19-positive tumors (n = 149); 2-year survival was 80 and 82%, respectively. Updated median TTF with afatinib and osimertinib was 28.1 months (90% CI: 26.8-30.3). Conclusion: Sequential afatinib/osimertinib was associated with encouraging OS/TTF in patients with EGFR T790M-positive non-small-cell lung cancer, especially in patients with Del19-positive tumors.
Ključne besede: non-small cell lung carcinoma - therapy, drug therapy, afatinib, osimertinib, GioTag study
Objavljeno v DiRROS: 11.09.2020; Ogledov: 1406; Prenosov: 1028
.pdf Celotno besedilo (1,58 MB)
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38.
Pulmonary pathology and COVID-19 : lessons from autopsy : the experience of European pulmonary pathologists
Fiorella Calabrese, Federica Pezzuto, Francesco Fortarezza, Paul Hofman, Izidor Kern, Angel Panizo, Jan von der Thüsen, Sergei Timofeev, Gregor Gorkiewicz, Francesca Lunardi, 2020, izvirni znanstveni članek

Povzetek: Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.
Ključne besede: COVID-19, SARS-CoV-2, autopsy, lung, pandemic
Objavljeno v DiRROS: 31.07.2020; Ogledov: 13335; Prenosov: 1143
.pdf Celotno besedilo (1,55 MB)
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39.
Coping strategies of patients with advanced lung or colorectal cancer in six European countries : insights from the ACTION study
Lea J. Jabbarian, Ida Joanna Korfage, Branka Červ, Johannes JM van Delden, Luc Deliens, Guido Miccinesi, Sheila Payne, Anna Thit Johnsen, Mariette Verkissen, Andrew Wilcock, Agnes van der Heide, Judith Anna Catharina Rietjens, 2020, pregledni znanstveni članek

Povzetek: Objective: Even when medical treatments are limited, supporting patients' coping strategies could improve their quality of life. Greater understanding of patients' coping strategies, and influencing factors, can aid developing such support. We examined the prevalence of coping strategies and associated variables. Methods: We used sociodemographic and baseline data from the ACTION trial, including measures of Denial, Acceptance and Problem-focused coping (COPE; Brief COPE inventory), of patients with advanced cancer from six European countries. Clinicians provided clinical information. Linear mixed models with clustering at hospital level were used. Results: Data from 675 patients with stage III/ IV lung (342, 51%) or stage IV colorectal (333, 49%) cancer were used; mean age 66 (10 SD) years. Overall, patients scored low on Denial and high on Acceptance and Problem-focused coping. Older age was associated with higher scores on Denial than younger age ([beta] = 0.05; CI[0.023; 0.074]), and patients from Italy ([beta] = 1.57 CI[0.760; 2.388]) and Denmark ([beta] = 1.82 CI[0.881; 2.750]) scored higher on Denial than patients in other countries. Conclusions: Patients with advanced cancer predominantly used Acceptance and Problem-focused coping, and Denial to a lesser extent. Since the studied coping strategies of patients with advanced cancer vary between subpopulations, we recommend taking these factors into account when developing tailored interventions to support patients' coping strategies.
Ključne besede: ACTION study, lung cancer, colorectal cancer, coping strategies
Objavljeno v DiRROS: 29.07.2020; Ogledov: 1690; Prenosov: 1136
.pdf Celotno besedilo (319,54 KB)
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40.
Outsourcing predictive biomarker testing in non-small cell carcinoma : a personal view of pathologists
Luka Brčić, Izidor Kern, 2020, kratki znanstveni prispevek

Ključne besede: non-small cell lung carcinoma, diagnostic pathology, predictive biomarkers
Objavljeno v DiRROS: 27.07.2020; Ogledov: 2120; Prenosov: 1090
.pdf Celotno besedilo (139,69 KB)
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