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184. Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma : an international multicenter studyLuka Brčić, Thomas Klikovits, Zsolt Megyesfalvi, Berta Mosleh, Katharina Sinn, Richard Hritcu, Viktoria Laszlo, Tanja Čufer, Aleš Rozman, Izidor Kern, Katja Mohorčič, 2021, original scientific article Abstract: Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [>/=1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.
Keywords: mesothelioma - anatomy and histology - analysis, 1malignant pleural mesothelioma, programmed death-ligand 1, programmed cell death 1, PD-L1
Published in DiRROS: 31.03.2021; Views: 1320; Downloads: 576
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185. Pogledi bolnikov in onkologov na uvajanje telemedicine v času epidemije covid-19Miha Oražem, Irena Oblak, Tanja Španić, Ivica Ratoša, 2020, original scientific article Abstract: Izhodišča: Pandemija koronavirusne bolezni 2019 (covid-19) je zaradi epidemioloških ukrepov, zlasti spodbujanja fizične distance, marsikje po svetu pospešila uvajanje telemedicine v klinično prakso. Zato smo želeli pridobiti stališča onkoloških bolnikov in zdravnikov do tovrstne obravnave v onkologiji. Metode: K izpolnjevanju dveh ločenih kvantitativnih vprašal-nikov smo med 27. majem in 11. junijem 2020 prek elektronske pošte ter s pomočjo Slovenskega združenja organizacij bolnikov z rakom (ONKO NET) povabili bolnike z rakom, ki so bili bodisi na aktivnem zdravljenju bodisi na sledenju po zaključenem zdravljenju, in zdravnike onkologe. Dodatno je bil v Sektorju radioterapije Onkološkega inštituta Ljubljana izveden presečni dan za bolnike med obsevanjem. Rezultati: Na spletni ali natisnjen vprašalnik za bolnike je odgovorilo 475 bolnikov, od tega 310 (65,3 %) na aktivnem onko-loškem zdravljenju in 132 (27,8 %) v fazi sledenja. Skoraj polovica bolnikov (48,4 %) je kot primarno diagnozo navedla rak dojk. Več kot desetina vseh (11,3 %) je zaradi pandemije želela opustiti zdravniški pregled. V zasebnem življenju jih pametni telefon ali tablico uporablja 72,4 % in vsaj 30 % bolnikov bi bilo pripravlje-nih v bodoče pogosteje uporabljati telemedicinske storitve. Od 168 povabljenih zdravnikov jih je na vprašalnik odgovoril 101 (60 %) in ocenil, da bi s pomočjo telemedicine lahko opravil 21 % (0%80 %) vseh svojih storitev. Če bi se sami znašli v vlogi bolnika, bi bila prip-ravljena po telemedicini poseči dobra polovica sodelujočih (54,5 %). Zaključki: Uporaba telemedicine v onkologiji bi bila ob upošteva-nju nekaterih omejitev sprejemljiva za pomemben del bolnikov in zdravnikov
Keywords: telemedicina, covid-19, onkologija
Published in DiRROS: 18.03.2021; Views: 1654; Downloads: 443
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186. Zdravljenje raka dojke z obsevanjemTanja Marinko, Marija Snežna Paulin-Košir, Andreja Gojkovič Horvat, Jasenka Gugić Kevo, Danijela Golo, Ivica Ratoša, Maja Ivanetič Pantar, 2020, not set Keywords: bolnice, zdravstveni nasveti
Published in DiRROS: 15.03.2021; Views: 1497; Downloads: 357
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187. Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategiesJean Bousquet, Jean-Paul Cristol, Wienczyslawa Czarlewski, Josep M. Antò i Boquè, Adrian Martineau, Tari Haahtela, Susana C. Fonseca, Guido Iaccarino, Hubert Blain, Alessandro Fiocchi, Nisera Bajrović, Natalija Edelbaher, Maja Jošt, Peter Kopač, Anja Koren, Mitja Košnik, Karmen Kramer Vrščaj, Samo Kreft, Nika Lalek, Bojan Madjar, Tonka Poplas-Susič, Irma Rozman Sinur, Tanja Soklič, Katja Triller Vadnal, Nadja Triller, Jure Urbančič, Mihaela Zidarn, 2020, review article Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR[gamma]:Peroxisome proliferator-activated receptor, NF[kappa]B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2[alpha]:Elongation initiation factor 2[alpha]). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Keywords: Covid-19, SARS-CoV-2, food, insulin resistance, obesity, Nrf2, nutrients, TRPA1
Published in DiRROS: 25.01.2021; Views: 1716; Downloads: 648
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189. NSCLC molecular testing in Central and Eastern European countriesAles Ryška, Peter Berzinec, Luka Brčić, Tanja Čufer, Rafal Dziadziuszko, Maya Gottfried, Ilona Kovalszky, Włodzimierz Olszewski, Buge Oz, Lukas Plank, József Tímár, 2018, original scientific article Abstract: Background: The introduction of targeted treatments for subsets of non-small cell lung cancer (NSCLC) has highlighted the importance of accurate molecular diagnosis to determine if an actionable genetic alteration is present. Few data are available for Central and Eastern Europe (CEE) on mutation rates, testing rates, and compliance with testing guidelines. Methods: A questionnaire about molecular testing and NSCLC management was distributed to relevant specialists in nine CEE countries, and pathologists were asked to provide the results of EGFR and ALK testing over a 1-year period. Results: A very high proportion of lung cancer cases are confirmed histologically/cytologically (75-100%), and molecular testing of NSCLC samples has been established in all evaluated CEE countries in 2014. Most countries follow national or international guidelines on which patients to test for EGFR mutations and ALK rearrangements. In most centers at that time, testing was undertaken on request of the clinician rather than on the preferred reflex basis. Immunohistochemistry, followed by fluorescent in situ hybridization confirmation of positive cases, has been widely adopted for ALK testing in the region. Limited reimbursement is a significant barrier to molecular testing in the region and a disincentive to reflex testing. Multidisciplinary tumor boards are established in most of the countries and centers, with 75-100% of cases being discussed at a multidisciplinary tumor board at specialized centers. Conclusions: Molecular testing is established throughout the CEE region, but improved and unbiased reimbursement remains a major challenge for the future. Increasing the number of patients reviewed by multidisciplinary boards outside of major centers and access to targeted therapy based on the result of molecular testing are other major challenges.
Keywords: non-small-cell lung carcinoma, molecular diagnostic techniques, EGFR mutations, ALK rearrangements, Central Europe, Eastern Europe
Published in DiRROS: 30.11.2020; Views: 1723; Downloads: 926
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190. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : final analysis of the GioTag studyMaximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Angela Märten, Tanja Čufer, 2020, original scientific article Abstract: Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment >/=10 months before data entry. Primary outcome was time on treatment; OS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients.
Keywords: non-small cell lung carcinoma -- therapy, drug therapy, afatinib, osimertinib, GioTag study
Published in DiRROS: 18.11.2020; Views: 1518; Downloads: 1258
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