1. Timski pristop k zdravljenju raka glave in vratuPrimož Strojan, Cvetka Grašič-Kuhar, Branko Zakotnik, 2025, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: timska obravnava, stranski učinki, bolniki, zdravstveni nasveti
Objavljeno v DiRROS: 07.08.2025; Ogledov: 367; Prenosov: 131
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2. Četrt stoletja specializacije iz internistične onkologije v SlovenijiErika Matos, Simona Borštnar, Cvetka Grašič-Kuhar, 2025, strokovni članek Povzetek: Sistemsko zdravljenje dokazano izboljša preživetje številnih
bolnikov z rakom. Nabor protirakavih zdravil se je v zadnjih
desetletjih močno povečal, z njimi zdravimo več kot polovico
obolelih. Specifičnost bolezni, specifičnost zdravljenja in zdravil, ki imajo pogosto zelo ozko terapevtsko okno, so zahtevale razvoj nove, od klasične interne medicine ločene specializacije, internistične onkologije. Specializacija iz internistične onkologije je kot samostojna veja specializacije iz interne medicine v Sloveniji priznana od leta 2000. Pojavnost raka v Sloveniji narašča, vse več je bolnikov, ki potrebujejo tudi sistemsko zdravljenje in obravnavo pri internistu onkologu. Žal pa skladno z rastjo števila bolnikov ne raste tudi število internistov onkologov, premajhne postajajo tudi obstoječe prostorske zmogljivosti.
Ključne besede: internistična onkologija, internisti onkologi, specializacije
Objavljeno v DiRROS: 18.07.2025; Ogledov: 357; Prenosov: 151
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4. Razvoj raziskav cirkulirajočih tumorskih celic pri raku dojk na Onkološkem inštitutu LjubljanaTanja Jesenko, Cvetka Grašič-Kuhar, Živa Pišljar, Simona Miceska, Veronika Kloboves-Prevodnik, Maja Čemažar, 2024, pregledni znanstveni članek Povzetek: Cirkulirajoče tumorske celice (CTC) so postale pomemben biološki označevalec pri raku dojk, saj omogočajo vpogled v razvoj in napredovanje razsejane bolezni ter spremljanje odziva na zdravljenje. Zaradi njihove izjemne redkosti in kompleksnosti sestave krvi, v kateri se nahajajo, sta njihova izolacija in karakterizacija velik izziv. Posebne metode izolacije omogočajo obogatitev CTC iz vzorca krvi in olajšajo nadaljnjo analizo. Na Onkološkem inštitutu Ljubljana smo leta 2018 začeli s prvimi koraki v smeri razvoja preproste metode za izolacijo in karakterizacijo CTC, ki bi omogočala prepoznavanje teh celic s citopatološkimi analizami. Ocenili smo dve različni metodi izolacije CTC pri bolnicah z rakom dojk, ki temeljita na različnih pristopih. Prva metoda temelji na bioloških lastnostih celic, kot je izražanje epitelijskega označevalca celične adhezije (EpCAM), medtem ko druga metoda temelji na fizikalnih lastnostih CTC, kot sta večja velikost in stisljivost v primerjavi z drugimi krvnimi celicami. Ugotovili smo, da je fizikalna metoda primernejša, saj omogoča izolacijo večjega števila morfološko ohranjenih CTC in tudi skupkov CTC. Po izolaciji pripravimo citološke preparate, ki jih nato opredelimo s citopatološko analizo in dodatnimi imunocitokemičnimi ter imunofluorescenčnimi barvanji. Na ta način lahko trenutno določimo število CTC in skupkov CTC v krvi, ocenimo njihovo morfološko ohranjenost ter prepoznamo njihov fenotip. Poleg preučevanja vzorcev posamičnih CTC in skupkov CTC v okviru trenutno potekajočih kliničnih raziskav in načrtovane vzpostavitve translacijske platforme na mišjih modelih, pa v prihodnosti želimo nabor raziskav CTC še razširiti na genomsko in transkriptomsko analizo.
Ključne besede: cirkulirajoče tumorske celice, rak dojk, eksperimentalna onkologija
Objavljeno v DiRROS: 21.05.2025; Ogledov: 461; Prenosov: 168
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5. Učinkovitost in varnost zdravljenja s trastuzumab derukstekanom : analiza podatkov iz realnega svetaNina Privšek, Simona Borštnar, Cvetka Grašič-Kuhar, 2024, izvirni znanstveni članek Povzetek: Nova generacija zdravil, ki se imenuje konjugat protitelesa in zdravila (ADC), trenutno predstavlja eno najučinkovitejših zdravil pri zdravljenju raka. Usmerjena je proti specifični tarči (antigenu), selektivno izraženi na tumorski celici, po vezavi nanjo sledi tarčna znotrajcelična dostava citostatika, ki povzroči celično smrt. Pri razsejanem raku dojk je ADC z imenom trastuzumab derukstekan (T-DXd) pokazal izjemno učinkovitost v več raziskavah pod imenom DESTINY. Naprej so bili na voljo podatki pri razsejanem HER2+ raku dojk, kasneje še pri drugih HER2+ solidnih rakih ter nato še pri raku dojk z nizko izraženostjo HER2. V prispevku predstavljamo prve podatke o učinkovitosti in varnosti T-DXd v Sloveniji. V retrospektivno raziskavo smo vključili bolnike, zdravljene na Onkološkem inštitutu Ljubljana od novembra 2021 do aprila 2024. Ugotavljamo dobre odgovore na zdravljenje (objektivni odgovor 59 % pri HER2+ raku dojk, 38 % pri drugih HER2+ solidnih rakih ter 33 % pri nizkem izražanju HER2). Po kratkem srednjem času spremljanja 8,8 (95 % IZ 0,8–33,3) meseca je preživetje brez progresa v realnem svetu (rwPFS) 13 mesecev pri HER2+ raku dojk, 5,8 meseca pri raku dojk z nizko izraženostjo HER2 in 7,7 meseca pri ostalih solidnih HER2+ ali HER2 mutiranih rakih. Varnostni profil je v skladu s poročili v registracijskih raziskavah, razen za pnevmonitis, ki smo ga beležili v bistveno nižjem odstotku (le 1 %). Zaključimo lahko, da je kljub poznim linijam zdravljenja in heterogeni populaciji delež odgovorov na T-DXd visok, ocena rwPFS pa je ob kratkem času spremljanja še nezanesljiva.
Ključne besede: rak dojk, HER2, trastuzumab derukstekan
Objavljeno v DiRROS: 21.05.2025; Ogledov: 386; Prenosov: 165
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6. Imunohistokemična analiza izražanja glukokortikoidnih receptorjev pri zgodnjem raku dojk in njihov vpliv na odgovor na zdravljenje z neoadjuvantno sistemsko terapijoMarjetka Sraka, Barbara Gazić, Primož Drev, Cvetka Grašič-Kuhar, 2024, izvirni znanstveni članek Povzetek: Glukokortikoidni receptor (GR) je različno izražen na tumorskih in imunskih celicah raka dojk, njegova izraženost pa je morda odvisna od molekularnega podtipa raka dojk, prav tako njegova izraženost morda vpliva na odgovor na neoad-juvantno sistemsko terapijo. Naš namen je vpeljati zanesljivo imunohistokemično barvanje s protitelesi proti GR, drugi namen pa je oceniti izraženost GR na vzorcih raka dojk in preučiti, ali se ta izraža različno pri različnih podtipih in ali njegova izraženost vpliva na odgovor na neoadjuvantno sistemsko terapijo.
Ključne besede: rak dojk, neoadjuvantno sistemsko zdravljenje, glukokortikoidni receptor
Objavljeno v DiRROS: 26.07.2024; Ogledov: 1011; Prenosov: 487
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7. The prognostic significance of tumor-immune microenvironment in ascites of patients with high-grade serous carcinomaSimona Miceska, Erik Škof, Simon Buček, Cvetka Grašič-Kuhar, Gorana Gašljević, Špela Smrkolj, Veronika Kloboves-Prevodnik, 2023, izvirni znanstveni članek Povzetek: Background: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS). Patients and methods: Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3+ T cells (CD4+, CD8+, Tregs, and NKT cells), B cells, NK cells (CD56brightCD16- and CD56dimCD16+ subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated. Results: CD3+ cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103+ expression was mostly present on CD8+, and not CD4+ cells. PD-1 was mainly expressed on CD3+ T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103+CD3+ T cells, PD-1+ Tregs, CD56brightCD16- NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8+ cells, macrophages, and PD-1+CD56brightCD16- NK cells, along with low percentages of CD4+ cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs. Conclusions: Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our finBackground: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS). Patients and methods: Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3+ T cells (CD4+, CD8+, Tregs, and NKT cells), B cells, NK cells (CD56brightCD16- and CD56dimCD16+ subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated. Results: CD3+ cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103+ expression was mostly present on CD8+, and not CD4+ cells. PD-1 was mainly expressed on CD3+ T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103+CD3+ T cells, PD-1+ Tregs, CD56brightCD16- NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8+ cells, macrophages, and PD-1+CD56brightCD16- NK cells, along with low percentages of CD4+ cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs. Conclusions: Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our findings.dings.
Ključne besede: high-grade serous carcinoma, immune cells, prognostic markers
Objavljeno v DiRROS: 26.07.2024; Ogledov: 1328; Prenosov: 638
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8. Changes in the quality of life of early breast cancer patients and comparison with the normative Slovenian populationCvetka Grašič-Kuhar, Tjaša Gortnar Cepeda, Christian Kurzeder, Marcus Vetter, 2023, izvirni znanstveni članek Povzetek: We aimed to identify changes in quality of life after breast cancer treatment and compare them withthe normative population data for the Slovenian population.Patients and methods. A prospective, single-group, cohort design was used. A total of 102 early breast cancerpatients treated with chemotherapy at the Institute of Oncology Ljubljana were included. Of those, 71% returned thequestionnaires after one-year post-chemotherapy. The Slovenian versions of the European Organisation for Researchand Treatment of Cancer (EORTC) QLQ C30 and BR23 questionnaires were used. Primary outcomes were a com-parison of global health status/quality of life (GHS) and C30 Summary Score (C30-SumSc) at baseline and one-yearpost-chemotherapy with the normative Slovenian population. The exploratory analysis evaluated the differences insymptoms and functional scales of QLQ C-30 and QLQ BR-23 between baseline and one-year post-chemotherapy.Results. At baseline and one-year post-chemotherapy, C30-SumSc of patients was lower than the predictedC30-SumSc from the normative Slovenian population by 2.6 points (p = 0.04) and 6.5 points (p < 0.001), resp. On thecontrary, GHS was not statistically different from predicted either at baseline or after one year. Exploratory analysisrevealed that one-year post-chemotherapy compared to the beginning of chemotherapy, patients had statisticallysignificantly and clinically meaningful lower scores in body image and cognitive functioning, and increased symptomscores for pain, fatigue, and arm symptoms.Conclusions. The C30-SumSc is reduced one- year post-chemotherapy. Early interventions should be directed to-ward the prevention of the decline of cognitive functioning and body image, and to alleviate fatigue, pain, and armsymptoms.
Ključne besede: breast cancer, chemotherapy, quality of life
Objavljeno v DiRROS: 25.07.2024; Ogledov: 726; Prenosov: 312
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9. Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolationTanja Jesenko, Živa Pišljar, Cvetka Grašič-Kuhar, Maja Čemažar, Urška Matkovič, Simona Miceska, Jerneja Varl, Anamarija Kuhar, Veronika Kloboves-Prevodnik, 2021, izvirni znanstveni članek Povzetek: Background. Circulating tumor cells (CTCs) have become an important biomarker in breast cancer. Different iso-lation tech-niques based on their biological or physical features were established. Currently, the most widely used methods for visualization after their separation are based on immunofluorescent staining, which does not provide the information on the morphology.Materials and methods. The aim of this study was to evaluate how two different separation techniques affect cell morphology and to analyse cell morphology with techniques used in routine cytopathological laboratory. A direct side-by-side comparison of physical (Parsortix%) and biological (MACS%) separation technique was performed.Results. In the preclinical setting, both isolation techniques retained the viability and antigenic characteristics of MCF7 breast cancer cells. Some signs of degeneration such as cell swelling, cytoplasmic blebs, villous projections and vacuolization were observed. In metastatic breast cancer patient cohort, morphological features of isolated CTCs were dependent on the separation technique. After physical separation, CTCs with preserved cell morphology were detected. After biological separation the majority of the isolated CTCs were so degenerated that their identity was difficult to confirm.Conclusions. Taken together, physical separation is a suitable technique for detection of CTCs with preserved cell morphology for the use in a routine cytopathological laboratory.
Ključne besede: circulating tumor cells, breast cancer, morphology
Objavljeno v DiRROS: 22.07.2024; Ogledov: 1117; Prenosov: 678
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