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1.
Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab : real-world experience
Nežka Hribernik, Marko Boc, Janja Ocvirk, Jasna Knez Arbeiter, Tanja Mesti, Marija Ignjatović, Martina Reberšek, 2020, original scientific article

Abstract: Based on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials. Patients and methods. This observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019. Results. The estimated median overall survival (OS) was 25.1 months (95% CI, 14.6%35.6) and the median progressionfree survival (PFS) was 10.7 months (95% CI, 5.9%15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3%4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment. Conclusions. Our real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.
Keywords: immunotherapy, pembrolizumab, metastatic melanoma, treatment-naive
Published in DiRROS: 11.07.2024; Views: 30; Downloads: 5
.pdf Full text (696,58 KB)

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Nuclear magnetic resonance metabolic fingerprint of bevacizumab in mutant IDH1 glioma cells
Tanja Mesti, Nadia Bouchemal, Claire Banissi, Mohamed N. Triba, Carole Marbeuf-Gueye, Maja Čemažar, Laurence Le Moyec, Antoine F. Carpentier, Philippe Savarin, Janja Ocvirk, 2018, original scientific article

Abstract: Malignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known. Materials and methods The immunoassay and MTT assay were used to assess the concentration of secreted VEGF and cell viability after bevacizumab exposure. Metabolomic studies on cells were performed using high resolution magic angle spinning spectroscopy (HRMAS). Results mIDH1-U87 cells secreted VEGF (13 ng/mL). Regardless, bevacizumab had no cytotoxic effect, even after a 72h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (polyunsaturated fatty acids [PUFA], glycerophosphocholine, and phosphocholine). Conclusions In mIDH1-U87 cells, changes in glutamine group metabolites and lipids were identified as metabolic markers of bevacizumab treatment. These data support the possibility of a functional tricarboxylic acid cycle that runs in reductive manner, as a probable mechanism of action of bevacizumab in IDH1 mutated gliomas and propose a new target pathway for effective treatment of malignant gliomas.
Keywords: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer, idh1 mutation, malignant glioma, bevacizumab, metabolic fingerprint
Published in DiRROS: 11.06.2024; Views: 76; Downloads: 37
.pdf Full text (511,70 KB)

4.
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, original scientific article

Abstract: 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.
Keywords: metastatic colorectal cancer, bevacizumab, chemotherapy, elderly
Published in DiRROS: 30.04.2024; Views: 262; Downloads: 82
.pdf Full text (620,74 KB)

5.
Malignant gliomas : old and new systemic treatment approaches
Tanja Mesti, Janja Ocvirk, 2016, review article

Abstract: Malignant (high-grade) gliomas are rapidly progressive brain tumours with very high morbidity and mortality. Until recently, treatment options for patients with malignant gliomas were limited and mainly the same for all subtypes of malignant gliomas. The treatment included surgery and radiotherapy. Chemotherapy used as an adjuvant treatment or at recurrence had a marginal role. Conclusions. Nowadays, the treatment of malignant gliomas requires a multidisciplinary approach. The treatment includes surgery, radiotherapy and chemotherapy. The chosen approach is more complex and individually adjusted. By that, the effect on the survival and quality of life is notable higher.
Keywords: malignant gliomas, systemic treatment, multidisciplinary, survival
Published in DiRROS: 30.04.2024; Views: 255; Downloads: 88
.pdf Full text (696,05 KB)

6.
Zdravljenje IDH1 astrocitoma : prikaz primera
Blaž Tomič, Tanja Mesti, 2024, published professional conference contribution

Keywords: internistična onkologija, astrocitom, kemoterapija
Published in DiRROS: 22.04.2024; Views: 197; Downloads: 65
.pdf Full text (821,57 KB)

7.
Konjugat protitelo-zdravilo trastuzumab-derukstekan pri zdravljenju HER2-pozitivnega rak želodca
Lucija Bogdan, Tanja Mesti, 2024, published professional conference contribution

Keywords: internistična onkologija, rak želodca, kemoterapija
Published in DiRROS: 22.04.2024; Views: 273; Downloads: 59
.pdf Full text (864,86 KB)

8.
Mutacije IDH : nova terapevtska tarča za zdravljenje tumorjev prebavil in možganskih tumorjev
Tanja Mesti, 2024, published professional conference contribution

Keywords: internistična onkologija, rak prebavil, rak možganskih tumorjev
Published in DiRROS: 19.04.2024; Views: 250; Downloads: 62
.pdf Full text (817,06 KB)

9.
LAG-3 - nova terapevtska tarča za zdravljenje tumorjev prebavil
Tanja Mesti, 2024, published professional conference contribution

Keywords: internistična onkologija, rak prebavil, imunoterapija
Published in DiRROS: 19.04.2024; Views: 258; Downloads: 106
.pdf Full text (819,97 KB)

10.
Cepiva za zdravljenje raka trebušne slinavke
Tanja Mesti, 2024, published professional conference contribution

Keywords: internistična onkologija, rak trebušne slinavke, cepiva
Published in DiRROS: 19.04.2024; Views: 180; Downloads: 49
.pdf Full text (744,40 KB)

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