1. The five-year KRAS, NRAS and BRAF analysis results and treatment patterns in daily clinical practice in Slovenia in 1st line treatment of metastatic colorectal (mCRC) patients with RASwild-type tumour (wtRAS) : a real- life data report 2013–2018Tanja Mesti, Martina Reberšek, Janja Ocvirk, 2023, original scientific article Abstract: Background. We preformed a Phase IV non-interventional study to assess KRAS, NRAS and BRAF status in metastatic colorectal cancer (mCRC) patients suitable for 1st line treatment and to evaluate the decisions for 1st line treatment considering the treatment goals in the RAS wild type (wt) patients. The aim of our study was also to evaluate the influ-ence of a waiting period for biomarkers analysis on the start of first-line treatment.Patients and methods. Patients with histologically confirmed mCRC adenocarcinoma suitable for first-line treat-ment fulfilling all inclusion criteria were included in the study. The KRAS, NRAS and BRAF analysis was performed from tissue samples of primary tumor site or metastatic site. All included patients have given consent to participate in the study by signing the informed consent form. Results. From April 2013 to March 2018 at the Institute of Oncology Ljubljana 650 patients were included, 637 of them were treated with first- line systemic treatment according to RAS and BRAF status. Remaining 13 patients with mCRC did not receive systemic first-line treatment. The distribution of patients with KRAS mutated and wild-type tumors, was almost equal, 48.8% and 47.9% respectively, 89 % of the patients had wt NRAS tumours and 86.1% had wt BRAF tu-mours. The most frequently prescribed treatment was bevacizumab-based therapy (53.1%), either in combination with doublet chemotherapy or with mono-chemotherapy. EGFR inhibitors cetuximab and panitumumab were prescribed in wt RAS mCRC patients (30.9%). The waiting period for biomarkers analysis was two weeks.Conclusions. Our real-world data, single centre 5-year analysis showed that the distribution between wild type and mutated type tumors of the patients with mCRC was approximately the same, as worldwide, so the Slovenian popula-tion with mCRC has the same ratio distribution of KRAS, NRAS and BRAF wild and mutated genes. We concluded that a two-week waiting period for biomarkers analysis did not influence the first line treatment decision, so it was in the accordance with the worldwide treatment guidelines based on evidence-based medicine.
Keywords: metastatic colorectal cancer, RAS and BRAF biomarkers, systemic treatment
Published in DiRROS: 25.07.2024; Views: 106; Downloads: 41
 Full text (367,23 KB) |
2. Prevalence of BRAF, NRAS and c-KIT mutations in Slovenian patients with advanced melanomaMaja Ebert Moltara, Srdjan Novaković, Marko Boc, Marina Bučić, Martina Reberšek, Vesna Zadnik, Janja Ocvirk, 2018, original scientific article Abstract: BRAF, NRAS and c-KIT mutations are characteristics of tumour tissues that influence on treatment decisions in metastatic melanoma patients. Mutation frequency and their correlation with histological characteristics in Slovenian population have not been investigated yet. Patients and methods. In our retrospective analysis we analysed mutational status of BRAF, NRAS and c-KIT in 230 pathological samples of patients who were intended to be treated with systemic therapy due to metastatic disease at the Institute of Oncology Ljubljana between 2013 and 2016. We collected also histological characteristics of primary tumours and clinical data of patients and correlated them with mutational status of tumour samples. Results. The study population consisted of 230 patients with a mean age 59 years (range 25%85). 141 (61.3%) were males and 89 (38.7%) females. BRAF mutations were identified in 129 (56.1%), NRAS in 31 (13.5%) and c-KIT in 3 (1.3%) tissue samples. Among the 129 patients with BRAF mutations, 114 (88.4%) patients had V600E mutation and 15 (11.6%) had V600K mutation. Patients with BRAF mutations tended to be younger at diagnosis (52 vs. 59 years, p < 0.05), patients with NRAS mutations older (61 vs. 55 years, p < 0.05). Number of c-KIT mutations were too low for any statistical correlation, but there was one out of 3 melanoma located in mucus membranes. Conclusions. The analysis detected high rate of BRAF mutations, low NRAS mutations and low c-KIT mutations compared to previously published studies in Europe and North America. One of the main reasons for this observation is specific characteristics of study population.
Keywords: BRAF, NRAS, c-KIT, melanoma
Published in DiRROS: 10.06.2024; Views: 151; Downloads: 78
Full text (291,53 KB)
This document has many files! More... |
3. Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitorsTanja Jesenko, Lara Prosen, Maja Čemažar, Tjaša Potočnik, Gregor Serša, 2016, original scientific article Abstract: 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.
Keywords: electrochemotherapy, BRAF inhibitors, vemurafenib, melanoma
Published in DiRROS: 30.04.2024; Views: 342; Downloads: 88
Full text (642,09 KB) |
