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1.
Is postmastectomy radiotherapy really needed in breast cancer patients with many positive axillary lymph nodes?
Tanja Marinko, Karmen Stanič, 2018, izvirni znanstveni članek

Povzetek: Postmastectomy radiotherapy (PMRT) improves survival by eliminating potential occult lesions in the chest wall and lymphatic drainage area. Meta-analysis has shown that PMRT reduces mortality and local recurrence of patients with node positive breast cancer (but there is no specific data about the effectiveness of PMRT in a subgroup of patients with a high number of positive axillary lymph nodes (PALN). The aim of the study was to analyse the impact of the number of PALN on local and distant metastasis occurrence, overall survival (OS) and distant metastases free survival (DMFS) in patients treated with PMRT. Patients and methods. We reviewed medical records of 129 consecutive breast cancer patients with PALN, treated at Institute of Oncology Ljubljana with PMRT between January 2003 and December 2004. We grouped patients according to the number of PALN as follows: Group 1 (less than 15 PALN) and Group 2 with more than 15 PALN. All patients received adjuvant systemic therapy according to the clinical guidelines. We analysed number of locoregional (LR) recurrences, distant metastasis, overall survival, progression free survival (PFS) and DMFS. Results. After the median follow-up time of 11.5 years, the Kaplan-Meier survival analysis of PALN showed significantly shorter OS (p = 0.006), shorter PFS (p = 0.002) and shorter DMFS (p < 0.001) in the group of > 15 PALN. Only one LR was found in the group of patients with more than 15 PALN. In multivariate analysis more than 15 PALN and treatment with anthracycline chemotherapy statistically significantly influenced OS and DMFS. For PFS presence of more than 15 PALN were the only independent factor of shorter survival. Conclusions. Patients with more than 15 PALN have shorter DMFS, PFS and OS as compared to patients with less than 15 PALN, though they receive the same LR treatment. More studies with higher number of patients included are needed to further evaluate our findings.
Ključne besede: radiotherapy, postmastectomy, axillary limph nodes, breast cancer
Objavljeno v DiRROS: 10.06.2024; Ogledov: 12; Prenosov: 5
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PD-L1 expression in squamous-cell carcinoma and adenocarcinoma of the lung
Urška Janžič, Izidor Kern, Andrej Janžič, Luka Čavka, Tanja Čufer, 2017, izvirni znanstveni članek

Povzetek: With introduction of immunotherapy (IT) into the treatment of advanced non-small-cell lung cancer (NSCLC), a need for predictive biomarker became apparent. Programmed death ligand 1 (PD-L1) protein expression is most widely explored predictive marker for response to IT. We assessed PD-L1 expression in tumor cells (TC) and immune cells (IC) of squamous-cell carcinoma (SCC) and adenocarcinoma (AC) patients. We obtained 54 surgically resected tumor specimens and assessed PD-L1 expression by immunohistochemistry after staining them with antibody SP142 (Ventana, USA). Clinicopathological characteristics were acquired from the hospital registry database. Results were analyzed according to cut-off values of % 5% and % 10% of PD-L1 expression on either TC or IC. 29 (54%) samples were AC and 25 (46%) were SCC. PD-L1 expression was significantly higher in TC of SCC compared to AC at both cut-off values (52% vs. 17%, p = 0.016 and 52% vs. 14%, p = 0.007, respectively) no difference in PD-L1 expression in IC of SCC and AC was found. In AC alone, PD-L1 expression was significantly higher in IC compared to TC at both cut-off values (72% vs. 17%, p < 0.001 and 41% vs. 14%, p = 0.008, respectively), while no significant difference between IC and TC PD-L1 expression was revealed in SCC. Our results suggest a significantly higher PD-L1 expression in TC of SCC compared to AC, regardless of the cut-off value. PD-L1 expression in IC is high in both histological subtypes of NSCLC, and adds significantly to the overall positivity of AC but not SCC.
Ključne besede: lung cancer, squamous-cell lung cancer, adenocarcinoma, tumor cells, immune cells, PD-L1 expression
Objavljeno v DiRROS: 31.05.2024; Ogledov: 83; Prenosov: 78
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Effects of electrochemotherapy with cisplatin and peritumoral IL-12 gene electrotransfer on canine mast cell tumors : a histopathologic and immunohistochemical study
Claudia Salvadori, Tanja Švara, Guido Rocchigiani, Francesca Millanta, Darja Pavlin, Maja Čemažar, Urša Lampreht Tratar, Gregor Serša, Nataša Tozon, Alessandro Poli, 2017, izvirni znanstveni članek

Povzetek: The study was aimed to characterize tumor response after combined treatment employing electrochemotherapy with IL-12 gene electrotransfer in dogs with spontaneous mast cell tumors (MCT). Materials and methods. Eleven dogs with eleven MCTs were included in the study. Histological changes were investigated in biopsy specimens collected before the treatment (T0), and 4 (T1) and 8 weeks (T2) later. Cellular infiltrates were characterized immunohistochemically by using anti CD3, CD20, Foxp3 (Treg), CD68 and anti MHC-class II antibodies. Proliferation and anti-apoptotic activity of neoplastic cells were assessed using anti Ki-67 and Bcl-2 antibodies. Angiogenetic processes were investigated immunohistochemically by using anti Factor VIII and anti CD31 antibodies and micro vessel density quantification. Results. Histopathological examination of samples at T0 confirmed the diagnosis and the presence of scanty infiltrates consisted mainly of T-lymphocytes and macrophages. At T1 and T2 neoplastic cells were drastically reduced in 7/11 cases, small clusters of neoplastic cells were detected in 3/11 cases and 1/11 cases neoplastic cells were still evident. Proliferation activity of neoplastic cells was significantly reduced at T1 and T2 and expression of anti-apoptotic protein at T1. Microvessel density was drastically reduced in all samples after treatment. The number of T-lymphocytes increased at T1, although not significant, while Treg were significant higher at T1 and macrophages at T2. Conclusions. The combined electrochemotherapy and IL-12 gene electrotransfer effectively induced a cellular response against neoplastic cells characterized mainly by the recruitment of T-lymphocytes and macrophages and a fibrotic proliferation with reduction of microvessels.
Ključne besede: histopathology, interleukin-12, elektroporation, electrochemotherapy, immune cells
Objavljeno v DiRROS: 31.05.2024; Ogledov: 78; Prenosov: 59
.pdf Celotno besedilo (956,49 KB)

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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: 119; Prenosov: 60
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Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitors
Tanja Jesenko, Lara Prosen, Maja Čemažar, Tjaša Potočnik, Gregor Serša, 2016, izvirni znanstveni članek

Povzetek: The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors. Materials and methods. ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL-28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status. Furthermore, the effectiveness of ECT in concomitant treatment with BRAF inhibitor vemurafenib was also determined in BRAF mutated cells SK-MEL-28 with clonogenic assay. Results. The survival of BRAF V600E mutated melanoma cells was even lower than non-mutated cells, indicating that ECT is effective regardless of the mutational status of melanoma cells. Furthermore, the synergistic interaction between vemurafenib and ECT with bleomycin was demonstrated in the BRAF V600E mutated melanoma cells. Conclusions. The effectiveness of ECT in BRAF mutated melanoma cells as well as potentiation of its effectiveness during the treatment with vemurafenib in vitro implies on clinical applicability of ECT in melanoma patients with BRAF mutation and/or during the treatment with BRAF inhibitors.
Ključne besede: electrochemotherapy, BRAF inhibitors, vemurafenib, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 202; Prenosov: 48
.pdf Celotno besedilo (642,09 KB)

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Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer : single center experience
Janja Ocvirk, Maja Ebert Moltara, Tanja Mesti, Marko Boc, Martina Reberšek, Neva Volk, Jernej Benedik, Zvezdana Hlebanja, 2016, izvirni znanstveni članek

Povzetek: Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients% register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. Patients and methods. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Results. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (% 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7%16.2) and 11.3 (95% CI, 10.2%12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4%28.9) and 27.4 (95% CI, 22.7%31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. Conclusions. In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and welltolerated regimen in elderly patients with metastatic colorectal cancer.
Ključne besede: metastatic colorectal cancer, bevacizumab, chemotherapy, elderly
Objavljeno v DiRROS: 30.04.2024; Ogledov: 176; Prenosov: 49
.pdf Celotno besedilo (620,74 KB)

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