1. Factors affecting attitudes towards COVID-19 vaccination : an online survey in SloveniaLuka Petravić, Rok Arh, Tina Gabrovec, Lucija Jazbec, Nika Rupčić, Nina Starešinič, Lea Zorman, Ajda Pretnar Žagar, Andrej Srakar, Matjaž Zwitter, Ana Slavec, 2021, izvirni znanstveni članek Opis: While the problem of vaccine hesitancy is not new, it has become more pronounced with the new COVID-19 vaccines and represents an obstacle to resolving the crisis. Even people who would usually trust vaccines and experts now prefer to wait for more information. A cross-sectional online survey was conducted in Slovenia in December 2020 to find out the attitudes of the population regarding COVID-19 vaccination and the factors that affect these attitudes. Based on 12,042 fully completed questionnaires, we find that higher intention to get vaccinated is associated with men, older respondents, physicians and medical students, respondents who got the influenza vaccination, those who knew someone who had gotten hospitalised or died from COVID-19 and those who have more trust in experts, institutions and vaccines. Nurses and technicians were less likely to get vaccinated. In answers to an open question, sceptics were split into those doubting the quality due to the rapid development of the vaccine and those that reported personal experiences with side effects of prior vaccinations. Although the Slovenian population is diverse in its attitudes towards vaccination, the results are comparable to those found in other countries. However, there are potential limitations to the generalizability of the findings that should be addressed in future studies. Ključne besede: cross-sectional studies, intention, public opinion, trust, ordinal regression, COVID-19, vaccination, surveys and questionnaires, Europe, immune system, SARS-CoV-2 Objavljeno v DKUM: 10.10.2024; Ogledov: 0; Prenosov: 10
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3. Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitorsMatjaž Zwitter, Antonio Rossi, Massimo Di Maio, Maja Pohar Perme, Gilberto Lopes, 2017, izvirni znanstveni članek Opis: Background: When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment.
Methods: Published documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson's correlation coefficient and the coefficient of determination, separately for first-line and second-line setting.
Results: The series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with nonsquamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR-mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months.
Conclusions: Most suitable candidates for intercalated treatment are treatment-naive patients with EGFR-mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted. Ključne besede: lung cancer, NSCLC, intercalated treatment, EGFR, tyrosine -kinase inhibitors Objavljeno v DKUM: 30.10.2017; Ogledov: 1387; Prenosov: 364
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5. Independent clinical research may alleviate disparities in cancer treatmentMatjaž Zwitter, 2016, izvirni znanstveni članek Opis: Disparities in cancer care are a reality of the modern world. Unfortunately, current clinical research is in the hands of for-profit pharmaceutical companies and of researchers from the developed world. Problems specific to cancer care in developing countries and among deprivileged populations are ignored. Independent clinical research can offer new valuable knowledge and identify affordable and cost-effective treatments. As such, research not depending on commercial sponsors should become one of the important avenues to alleviate the problem of cancer disparities. Ključne besede: clinical research, disparities in cancer care, cost-effective treatment Objavljeno v DKUM: 04.08.2017; Ogledov: 1388; Prenosov: 392
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6. Intermittent chemotherapy and erlotinib for nonsmokers or light smokers with advanced adenocarcinoma of the lung : a phase II clinical trialMatjaž Zwitter, Mirjana Rajer, Viljem Kovač, Izidor Kern, Martina Vrankar, Uroš Smrdel, 2011, izvirni znanstveni članek Opis: Background. Intermittent application of chemotherapy and tyrosine kinase inhibitors may avoid antagonism between the two classes of drugs. This hypothesis was tested in a Phase II clinical trial. Patients and Methods. Eligible patients were nonsmokers or light smokers, chemo-naïve, with metastatic adenocarcinoma of the lung. Treatment: 4 to 6 cycles of gemcitabine 1250 mg/m2 on days 1 and 4, cisplatin 75 mg/m2 on day 2, and erlotnib 150 mg daily on days 5–15, followed by erlotinib as maintenance. Results. 24 patients entered the trial. Four pts had grade 3 toxicity. Complete remission (CR) and partial remission (PR) were seen in 5 pts and 9 pts, respectively (response rate 58%). Median time to progression (TTP) was 13.4 months and median overall survival (OS) was 23 months. When compared to patients with negative or unknown status of EGFR mutations, 8 patients with EGFR gene activating mutations had significantly superior experience: 4 CR and 4 PR, with median TTP 21.5 months and OS 24.2 months (P < .05). Conclusions. Intermittent schedule with gemcitabine, cisplatin and erlotinib has mild toxicity. For patients who are positive for EGFR gene activating mutations, this treatment offers excellent response rate, time to progression and survival. Ključne besede: smokers, nonsmokers, cancer treatment, lung cancer, chemotherapy, erlotinib Objavljeno v DKUM: 14.06.2017; Ogledov: 1257; Prenosov: 189
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7. Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factorUroš Smrdel, Mara Popović, Matjaž Zwitter, Emanuela Boštjančič, Andrej Zupan, Viljem Kovač, Damjan Glavač, Drago Bokal, Janja Jerebic, izvirni znanstveni članek Opis: Background: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma.
Patients and methods: Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization).
Results: Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups.
Conclusions: Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored. Ključne besede: glioblastoma, long-term survival, methyl guanine methyl transferase, prognostic factor Objavljeno v DKUM: 05.04.2017; Ogledov: 1259; Prenosov: 476
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8. Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer : a randomized phase II clinical trialMartina Vrankar, Matjaž Zwitter, Tanja Bavčar-Vodovnik, Ana Milič, Viljem Kovač, 2014, izvirni znanstveni članek Opis: Background: The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid.
Patients and methods: Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60-66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1-5 and 29-33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).
Results: From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively.
Conclusions: Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance. Ključne besede: induction chemotherapy, non-small cell lung cancer, radiation therapy, randomized clinical trial Objavljeno v DKUM: 05.04.2017; Ogledov: 1374; Prenosov: 174
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9. Brain metastases in lung adenocarcinoma : impact of EGFR mutation status on incidence and survivalKarmen Stanič, Matjaž Zwitter, Nina Turnšek Hitij, Izidor Kern, Aleksander Sadikov, Tanja Čufer, 2014, izvirni znanstveni članek Opis: The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice. Patients and methods. We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival. Results. Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later. Conclusions. Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease. Ključne besede: brain metastases, lung adenocarcinoma, EGFR mutations Objavljeno v DKUM: 05.04.2017; Ogledov: 1202; Prenosov: 166
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10. Imunohisotkemični in geentski označevalci pri glioblastomu multiformeUroš Smrdel, 2015, doktorsko delo/naloga Opis: Glioblastom (GBM) je najpogostejši primarni možganski tumor. Njegova incidenca v Sloveniji znaša 2,9 bolnika na 100.000 prebivalcev. Na Onkološkem inštitutu Ljubljana smo v letih od 1997 do 2013 obravnavali 861 bolnikov z GBM, od teh jih je umrlo 730. Kljub slabi prognozi vedno več bolnikov preživi vsaj 2 leti in pol. Zanimalo nas je, v čem se ta skupina bolnikov razlikuje od večine bolnikov z GBM. Bolnike z GBM lahko razdelimo v prognostične skupine glede na klinične parametre, kot so starost, stanje zmogljivosti in obseg operacije glede na to jih lahko razdelimo naprej z rekurzivno particijsko analizo razrede. Naprej jih lahko opredelimo tudi glede na molekularne in genetske označevalce, kot so metilacija promotorja metil-gvanin-metil transferaze (MGMT), glede na nekatere podatke pa tudi mutacija izocitrat dehidrogenaze 1 (IDH1). Cilji naloge so bili opredeliti pojavljanje MGMT, IDH1in LoH1p/19q pri bolnikih z GBM z dolgim preživetjem in pri podobnih bolnikih, ki so imeli običajno preživetje. Hipoteza naše raziskave je bila, da lahko z uporabo imunohistokemičnih in genetskih označevalcev te skupine bolje opredelimo kakor z dosedaj uporabljanimi metodami. Pregledali smo populacijo bolnikov z GBM. Opredelili smo jih glede na klinične napovedne dejavnike, poiskali bolnike, ki so preživeli več kot 2 leti in pol in jim poiskali ustrezno kontrolno skupino. Pri obeh skupinah smo določili status metilacije promotorja MGMT, mutacije IDH1, IDH2, CDKN2A, CDKN2B in preureditev kromosomov 1p in 19q, opredelili smo tudi potrebo bolnikov po kortikosteroidih. Potrdili pomembnost RPA- razredov za preživetje. Opažamo značilno večjo incidenco metilacije promotorja MGMT, mutacije IDH1 R132H in nižjo potrebo po kortikosteroidih pri bolnikih z dolgim preživetjem. V multivariatni analizi sta se kot značilna za preživetje izkazala metilacija promotorja za MGMT, ki je prognostično ugodna in večja potreba po kortikosteroidih 3 mesece po zaključenem lokalnem zdravljenju, ki korelira s slabšim preživetjem. Izsledki raziskave potrjujejo prognostični pomen metilacije promotorja MGMT, še več, breztega praktično ni dolgega preživetja. Glede na to, da status metilacije promotorja MGMT ni stalno stanje, pač pa se lahko spreminja, se poraja vprašanje o dolgotrajni terapiji s kortikosteroidi. Z raziskavo smo potrdili pomen določanja imunohistokemičnih in genetskih označevalcev za napoved prognoze pri bolnikih z GBM. V prihodnje svetujemo rutinsko določanje metilacije promotorja MGMT ter določanje mutacij IDH1 in IDH2 na biopsijskih vzorcih GBM. Pri bolnikih, ki imajo metiliran promotor MGMT, so potrebne nadaljnje raziskave vpliva kortikosteroidov na metilacijski status promotorja MGMT. Ključne besede: glioblastom, dolgotrajno preživetje, MGMT, IDH1, kortikosteroidi, RPA Objavljeno v DKUM: 14.11.2016; Ogledov: 3491; Prenosov: 257
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