31. 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, izvirni znanstveni članek Povzetek: 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.
Ključne besede: BRAF, NRAS, c-KIT, melanoma
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32. Ocular changes in metastatic melanoma patients treated with MEK inhibitor cobimetinib and BRAF inhibitor vemurafenibAna Uršula Gavrič, Janja Ocvirk, Polona Jaki Mekjavić, 2018, izvirni znanstveni članek Povzetek: Mitogen-activated protein kinase kinase (MEK) inhibitor cobimetinib and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib have significantly improved the prognosis of BRAF-mutated metastatic melanoma. Some ocular symptoms and signs were recently recognized to follow this treatment. The study was aimed to investigate ocular toxicity in patients with metastatic melanoma treated with cobimetinib in combina-tion with vemurafenib.Patients and methods. In the prospective, observational study, patients with BRAF-mutated metastatic melanoma treated with cobimetinib in combination with vemurafenib at the Institute of Oncology Ljubljana were asked to par-ticipate. Ophthalmic examination was performed including measurement of visual acuity and intraocular pressure, slit lamp examination, funduscopy (CF), infrared-reflectance (IR) imaging and optical coherence tomography (OCT). Results. Five out of 7 patients noticed changes in vision few days after starting the therapy with cobimetinib. In all patients, small circular lesions, described as MEKAR lesions, were documented in outer retinal layers demonstrated with OCT, IR, and CF. Changes were in the center and/or scattered over the retina almost symmetrical in both eyes in 6 patients, and asymmetrical in one patient, the latter presented also with unilateral anterior uveitis and cystoid macular edema.Conclusions. Multiple bilateral foveal and extrafoveal small retinal lesions in the outer retinal layers develop in patients treated with MEK inhibitor in combination with BRAF inhibitor. Ophthalmologists and oncologists need to be aware of this common, yet relatively benign and often transient ocular side effect to avoid needless intervention, including the discontinuance of a potentially life-prolonging therapy.
Ključne besede: metastatic malignant melanoma, eye, MEK inhibitor, MEKAR
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33. 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
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34. Early cardiotoxicity after adjuvant concomitant treatment with radiotherapy and trastuzumab in patients with breast cancerTanja Marinko, Simona Borštnar, Rok Blagus, Jure Dolenc, Cvetka Bilban-Jakopin, 2018, izvirni znanstveni članek Ključne besede: radiotherapy, adjuvant radiotherapy, cardiotoxicity, breast cancer
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36. Long-term survival of locally advanced stage III non-small cell lung cancer patients treated with chemoradiotherapy and perspectives for the treatment with immunotherapyMartina Vrankar, Karmen Stanič, 2018, izvirni znanstveni članek Povzetek: Standard treatment for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year overall survival rates range between 15 and 25%, while long term survival data are rarely reported. Patients and methods A total of 102 patients with stage III NSCLC treated between September 2005 and November 2010 with induction chemotherapy and CCRT were included in this long term survival analysis. All patients were tested for PD-L1 status and expression of PD-L1 was correlated with overall survival (OS), progression free survival (PFS) and toxicities. Results The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year-survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1 months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1 status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005. The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to 21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and are significantly shorter for patients with PD-L1 expression. New treatment with check-point inhibitors combined with RT therefore seems reasonable strategy to improve these results.
Ključne besede: NSCLC, non-small cell lung cancer, locally advanced, immunotherapy, chemoradiotherapy
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37. The influence of genetic variability on the risk of developing malignant mesotheliomaAlenka Franko, Nika Kotnik, Katja Goričar, Viljem Kovač, Metoda Dodič-Fikfak, Vita Dolžan, 2018, izvirni znanstveni članek Ključne besede: malignant mesothelioma, genetic polymorphism, antioxidative enzymes, genetic variability
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