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Iskalni niz: "avtor" (Tanja Čufer) .

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Echocardiography and cardiac biomarkers in patients with non-small cell lung cancer treated with platinum-based chemotherapy
Daniel Omersa, Tanja Čufer, Robert Marčun, Mitja Lainščak, 2017, izvirni znanstveni članek

Povzetek: Background. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains an important cause of cancer death worldwide. Platinum-based chemotherapy (PBC) for NSCLC can modify outcome while the risk of cardiotoxicity remains poorly researched. We aimed to evaluate the incidence and severity of cardiac injury during PBC in patients with NSCLC and to identify patients at risk. Methods. This was a single-centre, prospective, observational study of patients with early and advanced stage NSCLC referred for PBC. In addition to standard care, patients were examined and evaluated for cardiotoxicity before the first dose (visit 1), at the last dose (visit 2) and 6 months after the last dose of PBC (visit 3). Cardiotoxicity (at visit 2 and 3) was defined as increase in the ultrasensitive troponin T, N-terminal pro-B type natriuretic peptide or decrease in left ventricular ejection fraction (LVEF). Results. Overall, 41 patients (mean age 61 +/- 9; 54% men; 68% advanced lung cancer) were included. The median number of PBC cycles was 4. During the study period, there were no incidents of heart failure, and 3 deaths caused by tumour progression were recorded. The mean values of biomarkers and LVEF did not change significantly (p > 0.20). However, 10 (25%) had cardiotoxicity which was independently associated with a history of ischemic heart disease (p = 0.026). Conclusions. In NSCLC, cardiac assessment and lifestyle modifications may be pursued in patients with a history of cardiac disease and in patients with longer life expectancy.
Objavljeno v DiRROS: 10.05.2024; Ogledov: 98; Prenosov: 55
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The prognostic value of whole blood SOX2, NANOG and OCT4 mRNA expression in advanced small-cell lung cancer
Eva Sodja, Matija Rijavec, Ana Koren, Aleksander Sadikov, Peter Korošec, Tanja Čufer, 2016, izvirni znanstveni članek

Povzetek: The data on expression and clinical impact of cancer stem cell markers SOX2, NANOG and OCT4 in lung cancer is still lacking. The aim of our study was to compare SOX2, NANOG and OCT4 mRNA expression levels in whole blood between advanced small-cell lung cancer (SCLC) patients and healthy controls, and to correlate mRNA expression with progression-free survival (PFS) after first-line chemotherapy and overall survival (OS) in advanced SCLC patients. Patients and methods. 50 advanced SCLC patients treated with standard chemotherapy and followed at University Clinic Golnik, Slovenia, between 2009 and 2013 were prospectively included. SOX2, NANOG and OCT4 mRNA expression levels were determined using TaqMan qPCR in whole blood collected prior to chemotherapy. Whole blood of 34 matched healthy individuals with no cancerous disease was also tested. Results. SOX2 mRNA expression was significantly higher in whole blood of SCLC patients compared to healthy controls (p = 0.006). Significant correlation between SOX2 mRNA expression levels and the number of distant metastatic sites was established (p = 0.027). In survival analysis, patients with high SOX2 expression had shorter OS (p = 0.017) and PFS (p = 0.046). In multivariate Cox analysis, an independent value of high SOX2 expression for shorter OS (p = 0.002), but not PFS was confirmed. No significant differences were observed for NANOG or OCT4 expression levels when comparing SCLC patients and healthy controls neither when analysing survival outcomes in SCLC patients. Conclusions. SOX2 mRNA expression in whole blood might be a promising non-invasive marker for molecular screening of SCLC and important prognostic marker in advanced chemotherapy-treated SCLC patients, altogether indicating important role of cancer stem-like cell (CSC) regulators in cancer spread. Further evaluation of SOX2 as a possible screening/prognostic marker and a therapeutic target of SCLC is warranted.
Ključne besede: small-cell lung cancer, cancer stem cell markers, prognosis
Objavljeno v DiRROS: 30.04.2024; Ogledov: 122; Prenosov: 38
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Febrile neutropenia in chemotherapy treated small-cell lung cancer patients
Renata Režonja, Iztok Grabnar, Tomaž Vovk, Aleš Mrhar, Viljem Kovač, Tanja Čufer, 2015, izvirni znanstveni članek

Povzetek: Chemotherapy with platinum agent and etoposide for small-cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrileneutropenia. Primary prophylaxis with granulocyte colonystimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels inthe same patients. The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored. Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with febrile neutropenia. Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.
Ključne besede: small cell lung cancer, platinum-etoposide chemotherapy, etoposide, febrile neutropenia, plasma drug concentration
Objavljeno v DiRROS: 22.04.2024; Ogledov: 120; Prenosov: 58
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Brain metastases in lung adenocarcinoma : impact of EGFR mutation status on incidence and survival
Karmen Stanič, Matjaž Zwitter, Nina Turnšek, Izidor Kern, Aleksander Sadikov, Tanja Čufer, 2014, izvirni znanstveni članek

Povzetek: 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 DiRROS: 11.04.2024; Ogledov: 261; Prenosov: 36
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Oral treatment with etoposide in small cell lung cancer - dilemmas and solution
Renata Režonja, Lea Knez, Tanja Čufer, Aleš Mrhar, 2013, pregledni znanstveni članek

Povzetek: Background. Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be atrisk for excess toxicity. Conclusions. The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.
Ključne besede: oral etoposide, bioavailability, pharmacokinetic variability, small cell lung cancer, treatment
Objavljeno v DiRROS: 22.03.2024; Ogledov: 116; Prenosov: 38
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Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting
Mirko Lekić, Viljem Kovač, Nadja Triller, Lea Knez, Aleksander Sadikov, Tanja Čufer, 2012, izvirni znanstveni članek

Povzetek: Background. Small cell lung cancer (SCLC) represents approximately 13 tomediansurvival of SCLC patients treated by specific therapy (chemotherapy andžor radiotherapy) with regard to the 18%months in patients treated with standard chemotherapy and radiotherapy. Inpresence or absence of brain metastases at the time of diagnosis. Patients and methods. All SCLC patients have been treated in a routine clinical practice and followed up at theUniversity Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. Results. We found 251 patients eligible for the study. The median age of them was 65 years, majoritywere male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients(25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmedby a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. (Abstract truncated at 2000 characters)
Ključne besede: pljuča, rak (medicina), drobnocelični rak, metastaze, možgani
Objavljeno v DiRROS: 22.03.2024; Ogledov: 113; Prenosov: 41
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Adjuvant treatment of breast cancer patients with trastuzumab
Erika Matos, Tanja Čufer, 2007, pregledni znanstveni članek

Povzetek: Background. Trastuzumab is a monoclone antibody directed against HER2 receptors that are overexpressed in approximately 20% of breast cancer patients. The present paper presents five clinical trials in which trastuzumabwas applied in breast cancer patients in adjuvant setting. The results of all the trials consistently demonstrate a high efficacy of this target drug in the patients with HER2 positive tumours. So far, no formal guidelines for using trastuzumab in adjuvant setting for breast cancer have been approved. The reasons are many: (i) mean observation time in the studies done so far was considerably short; (ii) the drug was used according to different schedules, (iii) the overall time of treatment with trastuzumab was different in each trial, (iv) late side effects of treatment with trastuzumab are inadequately investigated, and (v) nobody can so far say for sure for which HER2 status patients therapy with trastuzumab is really beneficial. Conclusions. Trastuzumab is definitely very helpful in the treatment of the HER2-positive breast cancer patients that are hormone-independent and of anatomically larger tumours; but, what the absolute benefit of trastuzumab therapy in the treatment of small hormone-dependent tumours is remains a mystery. Incidentally, it must be borne in mind that cardiotoxicity, the well known side effect, may put particularly elderly patients at risk of death, thus beating any treatment advantages down. It has also not been yet resolved at what time it would be most appropriate to start with the therapy with trastuzumab, what would be the optimal duration of the therapy and whether trastuzumab is to be administered concurrently with chemotherapy or immediately after it? What is the optimal treatment duration, one or two yearsor only a few months? In addition there is still a question of optimal HER2 status determination and which HER2 status predicts for trastuzumab benefit. (Abstract truncated at 2000 characters)
Objavljeno v DiRROS: 22.02.2024; Ogledov: 297; Prenosov: 43
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Clinical utility of serine proteases in breast cancer
Tanja Čufer, 2004, strokovni članek

Povzetek: The serine protease uPA and its inhibitor PAI-1 are involved in the degradation of tumor stroma and basement membrane. The independent prognostic value of serine protease urokinase-type plasminogen activator uPA and its inhibitor PAI-1 in breast cancer has been almost uniformly confirmed in numerous individual studies as well as in a meta-analysis, including 18 data sets of more than 8,000 patients. According to these observations, the risk ofrelapse in node negative patients with low levels of uPA and PAI-1 is less then 10%; these patients could be spared from toxic adjuvant systemic therapy.Clinically relevant and even more important is the information that uPA and its inhibitor PAI-1 may also have a predictive value for response to either hormonal or cytotoxic therapy in early breast cancer. According to our data obtained from altogether 460 operable breast cancer patients, uPA and PAI-1 may have a predictive value for the response to hormone therapy, but notto chemotherapy. The high PAI-1 levels were associated with a higher risk of relapse in the patients without adjuvant systemic therapy (HR 2.14; C.I. 95%= 0.48-9.56; p=0.321) and in the patients treated with chemotherapy (RR 2.48; C.1. 95%=1.35-4.57; p=0.003). However, in the patients treated with adjuvant hormone therapy, either alone or in combination with chemotherapy, the prognosric value of uPA and PAI-1 was diminished. Moreover, high levels ofboth uPA and PAI-1 were associated with a lower risk of relapse (HR 0.79; p=0.693 and HR 0.26 p= 0.204, respectively). On the basis of currently available evidence, serine protease uPA and its inhibitor PAI-1 are certainly the markers that improve a proper selection of candidates for adjuvant systemic therapy and may also be the markers that could facilitate treatment decision in each individual patient, which is of utmost importance.
Objavljeno v DiRROS: 13.02.2024; Ogledov: 171; Prenosov: 41
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Electrochemotherapy with cisplatin of breast cancer tumor modules in a male patient
Martina Reberšek, Tanja Čufer, Zvonimir Rudolf, Gregor Serša, 2000, izvirni znanstveni članek

Povzetek: Background. The metastases of breast cancer in a male patient were treated with electrochemotherapy by intratumoral injection of cisplatin. Electrochemotherapy is chemotherapy with the subsequent local application of electric pulses to the tumor nodules in order to increase drug delivery into the cells. Case report. Cutaneous metastases of breast cancer were treated with the intratumoral administration of cisplatin and by 8 electric pulses (1300 V/cm) applied a minute later to each cutaneous metastasis. The treatmentresulted in complete response of two electrochemotherapy treated cutaneous metastases and partial response of the third metastasis. In cutaneous metastases treated with intratumoral administartion of cisplatin without electric pulses, only partial response was obtained. Conclusion. This study confirms that electrochemotherapy with cisplatin is effective in the treatment of breast cancer metastases, too, as it was already proved for electrochemotherapy with bleomycin.
Objavljeno v DiRROS: 25.01.2024; Ogledov: 189; Prenosov: 46
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Do we need axillary dissection in early breast cancer?
Tanja Čufer, 2000, objavljeni znanstveni prispevek na konferenci

Povzetek: Background. In the existing paradigm of the invasive breast cancer, the treatment with the axillary lymphnode dissection (ALND) and histologic stagingof the axilla, which is associated with a substantial morbidity, is considered necessary for the treatment decision and local control of disease. However paradigms are changing and, since primary tumor characteristics are increasingly used for treatment decision and since there is a trend towards the broad application of preoperative chemotherapy, ALND is less and less important for the treatment planning. In a small subgroup of patients in whom the information on nodal status is still important it can be obtained accurately by the sentinel lymph node biopsy. For good local control of the disease, ALND can be replaced with irradiation of the axilla with substantially lesser morbidity. Conclusions. Abandoning ALND together with breast conserving surgery is one of the major steps towards less mutilating surgery leading to a better quality of life of breast cancer patients at the end of this millennium.
Objavljeno v DiRROS: 25.01.2024; Ogledov: 194; Prenosov: 43
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