Faculty of Medicine

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The highest frequency of BRCA1 c.3700_3704del detected among Albanians from Kosovo
(Greater Poland Cancer Centre, Poland, 2022)
Kostovska Maleva, Ivana
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Jakovchevska, Simona
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Özdemir, Milena Jakimovska
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Kiprijanovska, Sanja
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Kubelka-Sabit, Katerina
Background: The spectrum of BRCA1 and BRCA2 mutations varies among populations; however, some mutations may be frequent in particular ethnic groups due to the “founder” effect. The c.3700_3704del mutation was previously described as a recurrent BRCA1 variant in Eastern European countries. This study aimed to investigate the frequency of c.3700_3704del BRCA1 mutation in Albanian breast and ovarian cancer patients from North Macedonia and Kosovo. Materials and methods: A total of 327 patients with invasive breast and/or ovarian cancer (111 Albanian women from North Macedonia and 216 from Kosovo) were screened for 13 recurrent BRCA1/2 mutations. Targeted NGS with a panel of 94 cancer-associated genes including BRCA1 and BRCA2 was performed in a selected group of 118 patients. Results: We have identified 21 BRCA1/2 pathogenic variants, 17 (14 BRCA1 and 3 BRCA2) in patients from Kosovo (7.9%) and 4 (1 BRCA1 and 3 BRCA2) in patients from North Macedonia (3.6%). All BRCA1/2 mutations were found in one patient each, except for c.3700_3704del BRCA1 mutation which was observed in 14 unrelated families, all except one originating from Kosovo. The c.3700_3704del mutation accounts for 93% of BRCA1 mutation positive cases and is present with a frequency of 6% among breast cancer patients from Kosovo. Conclusions: This is the first report of BRCA1/2 mutations among breast and ovarian cancer patients from Kosovo. The finding that BRCA1 c.3700_3704del represents a founder mutation in Kosovo with the highest worldwide reported frequency supports the implementation of fast and low-cost screening protocol, regardless of the family history and even a pilot population-based screening in at-risk population.
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Real-world data of cardiotoxicity during long-term therapy with trastuzumab in human epidermal growth factor receptor-2-positive metastatic breast cancer
(National Library of Serbia, 2022-12-16)
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Lazareva, Emilija
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Introduction/Objective. This study aims to investigate the cardiotoxicity of long-term therapy with trastuzumab in patients with HER2 positive metastatic breast cancer. Methods. A total of 48 patients with metastatic HER2 positive breast cancer were analyzed. The patients received long-term trastuzumab (time of application was longer than 20 months). The analyzed characteristics of the patients were: age, initial stage of the disease, application of anti-HER2 therapy and anthracyclines in the adjuvant setting, the number and type of applied systemic therapies concomitant with trastuzumab in the metastatic setting. Cardiac toxicity was assessed using left ventricular ejection fraction (LVEF) values at three time points: at the beginning, in the middle, and at the end of treatment period for each patient separately. Results. In 17 (35.4%) patients the trastuzumab treatment was temporary discontinued. The average time of trastuzumab therapy interval was 52.2 ? 23.5 months. The mean LVEF values were 66.73 ? 7.02%, 64.62 ? 5.7% and 63.44 ? 6.1%, respectively. The mean values of LVEF differed significantly in the observed three time points (F=4.9 p=0.009). Post hoc pairwise comparison, using Bonferonni correction, confirmed significantly lower mean LVEF values at the end point (at the end of treatment) compared with the mean LVEF values at the beginning of anti-HER2 treatment (p = 0.019), but within the reference range of LVEF ?50%. Conclusion. The data confirm good safety profile of long-term trastuzumab therapy in HER2 positive metastatic breast cancer patients considering cardiotoxicity.
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Prevention of chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients receiving adjuvant chemotherapy: Single institution experience
(2020)
Iljovska, Marina
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Lazareva, Emilija
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Introduction. The modern treatment of malignant diseases and the use of antineoplastic agents pose numerous challenges in terms of the side effects from applied specific oncological treatment. Despite to the significant progress in recent years, emesis and nausea are the two most common and most stressful side effects of cancer treatment and their successful management is still a great challenge. Chemotherapy-induced vomiting or nausea (CINV) significantly affects the quality of life of patients, can cause metabolic disorders, diarrhea, eating disorders and general physical and mental disorders and can question the further anti-tumor treatment of the patient. The prevention and the treatment of CINV and antiemetic therapy have central role in modern protocols for oncological treatment of malignant diseases, including breast cancer patients. Aim. The aim of our study was to obtain data about the efficacy of antiemetic prophylaxis in patients with breast cancer who received chemotherapy following the EC75 protocol in adjuvant setting and the compliance of the patients for the both acute and delayed emesis and nausea. Materials and methods. A prospective study was conducted in 32 breast cancer patients receiving chemotherapy following an EC75 protocol in an adjuvant setting for four consecutive chemotherapy cycles between February 2015 and June 2015. All patients received adequate premedication on day 1 prior to chemotherapy and appropriate oral postmedication was recommended in day 2-5 (with 5-HT3 antagonist and corticosteroid). The occurrence of acute and delayed nausea and emesis as well as taking the recommended postmedicaton by patients was evaluated through a specially structured questionnaire that beside general information contained the following information: the appearance of emesis and nausea within 24 hours after receiving chemotherapy and within the next 10 days, taking the recommended postmedication and the number of taken tablets and taking additional therapy besides the recommended. Results. Out of 32 patients, acute onset of nausea, nausea till day 5 and nausea from 5 to 10 day was recorded in 50%, 44% and 31% of patients, respectively. The results of the occurrence of acute emesis, emesis to to day 5 and nausea from 5 to 10 day were 16%, 9% and 0% respectively. Patients who received complete postmedication have reported acute nausea, nausea till day 5 and nausea from 5 to 10 day in 50%, 50% and 20%, while in patients with partial postmedication 50%, 59% and 39%, respectively. Conclusion. The obtained results do not indicate that acute and delayed nausea are more difficult to control. In patients’ good compliance, better control of both acute and postponed emesis is achieved, although the results obtained in patients with partial compliance may be due to failure to follow the recommended treatment. Despite the effectiveness of antiemetic prophylaxis and good compliance, there is a possibility for its improvement with introduction of new generations of antiemetics. Keywords: Chemotherapy, emesis, nausea, breast cancer, compliance
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Adjuvant chemotherapy plus concurrent chemoradiotherapy (CCRT) in advanced gastric adenocarcinoma treatment as standard of care
(2020)
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Lazarova, Emilija
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Berat, Meri
Introduction. Despite a worldwide decline in incidence based on GLOBOCAN 2018 data, stomach cancer is the 5th most common neoplasm and the 3rd most deadly cancer. In 90% of cases, its histology is adenocarcinoma, either of the intestinal type or of diffuse. Helicobacter pylori infection, smoking, salt and nitrate-rich foods are the most important factors of risk. The interactions between dietary factors, environmental factors and the development of gastric cancer are well described with clearly identified dietary exposures strongly associated with gastric cancer induction and prevention. Postoperative fluoropyrimidine-based CCRT and chemotherapy is standard adjuvant treatment of resected gastric adenocarcinoma. Materials and methods. Patients with subtotal gastrectomy and D1 lymph node dissection were treated with 2 cycles of Capecitabine (DD 2500 mg/m2 po bid/21day cycle) followed by chemoradiotherapy and another of 2 cycles chemotherapy with Capecitabine (DD 2500 mg/m2 po bid/21d cycle). CT simulation with oral contrast application was performed followed by delineation of target volumes and organs at risk according to CRITICS protocol. 3D conformal postoperative chemoirradiation was delivered with standard fractionation (TTD 50.4 Gy/1.8 Gy) with concurrent application of Capecitabine 1650mg/m2/bid/d1-5. Adjuvant treatment was delivered in postoperative period of 6 months. Results. Adjuvant chemotherapy and chemoradiotherapy prolongs disease free survival (DFS) and improves quality of life. CT-based 3D conformal treatment planning and delivery of postoperative chemoirradiation is minimum standard of care of gastric cancer treatment. Conclusion. Multidisciplinary decision making team approach is preferred. Primary treatment option for patients with potentially resectable locoregional gastric tumors is surgery. The guidelines have included postoperative chemo/chemoradiotherapy treatment depending of tumor stage, nodal status, extent of lymph node dissection and other risk factors (differentiation, lymphovascular invasion, neural invasion, surgical margins). Adjuvant chemotherapy and chemoradiotherapy prolongs disease free survival (DFS) and improves quality of life. Keywords: Gastric cancer, chemoirradiation, CCRT, DFS, 3D conformal, postoperative
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POSTOPERATIVE ADJUVANT INTENSITY-MODULATED RADIOTHERAPY FOR RADICALLY RESECTED RECTAL ADENOCARCINOMA: DATA FROM EVERYDAY PRACTICE
(Faculty of Medicine, University Ss. Cyril and Methodius in Skopje, 2022-05-04)
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Grozdanovska, Biljana
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Introduction: Adjuvant radiochemotherapy is a standard treatment in patients with surgically treated stage II or III rectal adenocarcinoma who did not undergo neoadjuvant radiotherapy. Intensity-modulated radiation therapy (IMRT) was only marginally investigated in postoperative setting. Material and methods: A longitudinal observational analysis was conducted in patients with radically resected stage II or III rectal adenocarcinoma treated with IMRT at the University Clinic for Radiotherapy and Oncology as part of the adjuvant postoperative treatment. The dose-volume parameters of the radiotherapy plans, as well as acute side effects of 40 patients were analyzed. Results: The average dose received by the target volume was 49.95 Gy (range 27-54 Gy). The mean volume of peritoneal cavity receiving 45 Gy (V45) was 102.73 cm3 (±52.10), V30 for pelvic bones was 38.3% (±5.48), V40 for bladder 52.48% (±10.9). The most frequent acute side effects were diarrhea in 17 (42.5%), lymphopenia in 34 (85%) and thrombocytopenia in 26 patients (65%). Most of the side effects were self-limiting and caused disruption of the radiation treatment only in 3 patients (7.5%). Conclusion: Integrating IMRT in the adjuvant treatment of locally advanced rectal cancer provides a good dose distribution and organs at risk sparing. The treatment is well tolerated, the side effects are mainly of lesser degrees and easily managed. A prospective trial comparing IMRT with 3-dimensional conformal radiotherapy is needed to assess whether IMRT offers a better perspective for adjuvant treatment. Keywords: rectal adenocarcinoma, adjuvant treatment, remove adjuvant treatment, intensity-modulated radiotherapy, acute side effects
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DUAL HER2 BLOCKADE WITH TRASTUZUMAB AND PERTUZAMB IN HER2- POSITIVE BREAST CANCER: SINGLE CENTER REAL WORLD DATA
(Macedonian Association of Anatomists, 2020-12-30)
Lazareva, Emilija
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Agents targeting the human epidermal growth factor receptor 2 (HER2) have improved outcomes of advanced HER2-positive breast cancer with durable responses. We evaluated therapy with trastuzumab and pertuzumab in early and metastatic HER2-positive breast cancer patients. In this paper we discuss the practicalities of treating patients with this combination with a particular focus on treatment in the single center setting. We retrospectively identifed patients on adjuvant and frst-line anti-HER2 therapy at The University Clinic of Radiotherapy and Oncology Skopje for at least 1 year from 2019 to 2020. Demographics, treatments and adverse events were recorded. The combination of pertuzumab–trastuzumab has established efficacy in patients with HER2‐positive advanced/metastatic breast cancer. Management of treatment related side‐effects such as diarrhea, febrile neutropenia and neuropathy typically include dose reduction or switching taxane. Specific patients with poorer tolerance of chemotherapy such may require particular management strategies.The roles of trastuzumab and pertuzumab are now very well established in the frst-line setting; identifying predictors of long-term response to these would be important in selecting which patients might beneft from entry into future clinical trials assessing the long-term beneft of these newer agents in addition.

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