1. 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: 26; Downloads: 20
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2. Napovedovanje neželenih učinkov pri imunoterapiji metastatskega melanoma na podlagi slik FDG-PETKatja Strašek, Martina Reberšek, 2024, published professional conference contribution Abstract: Imunoterapija je preoblikovala zdravljenje metastatskih rakov, saj je izboljšala preživetje in kakovost življenja bolnikov. Kljub temu povzroča imunsko pogojene neželene učinke, ki zahtevajo prekinitev zdravljenja. Njihovo zgodnje odkrivanje je zato ključnega pomena, njihova diagnoza pa temelji predvsem na kliničnih simptomih in laboratorijskih izvidih. Razmah razvoja umetne inteligence v preteklih letih je omogočil bolj kvantitativno analizo 18F-FDG PET/CT slik. Prvi korak, kjer umetna inteligenca pripomore k hitrejši diagnozi imunsko pogojenih neželenih učinkov, so nevronske mreže, razvite za segmentacijo organov na CT-slikah. Uporaba takšnih avtomatskih orodij za segmentacijo organov je hitrejša in bolj natančna v primerjavi z ročno segmentacijo. Omogoča tudi razvoj kvantitativnih slikovnih bioloških označevalcev, izvlečenih iz PET-slik s pomočjo pridobljenih segmentacij, kar je pripomoglo tudi k razmahu razvoja napovednih modelov. V retrospektivni raziskavi, ki je vključevala 58 bolnikov z metastatskim melanomom, so se percentili porazdelitve FDG v ščitnici, črevesju in pljučih izkazali kot orodje za ločevanje med bolniki, ki bodo razvili imunsko pogojene neželene učinke, in tistimi, ki jih ne bodo. Validacija teh kvantitativnih slikovnih bioloških označevalcev (angl. Quantitative Imaging Biomarkers, QIB) za napovedovanje imunsko pogojenih neželenih učinkov trenutno poteka v prospektivni neinterventni klinični raziskavi na Onkološkem inštitutu Ljubljana. Prvi izsledki kažejo, da so razviti označevalci v pomoč klinikom pri zgodnji diagnozi imunsko pogojenih neželenih učinkov, kar omogoči hitrejše ukrepanje pred razvojem kliničnih simptomov, a včasih tudi lažno napovedo možen razvoj neželenih učinkov. Naslednji koraki so razvoj modela za napoved časa razvoja imunsko pogojenih neželenih učinkov, a je za razvoj takšnih modelov potrebno večje število podatkov, za kar so potrebne multicentrične klinične raziskave. 18 Ključne besede: imunoterapija, neželeni učinki, kvantifikacija, FDG-PET/CT, napovedovanje neželenih učinkov, kvantitativni slikovni biološki označevalci
Keywords: metastatski melanom, imunoterapija, neželeni učinki
Published in DiRROS: 06.06.2024; Views: 55; Downloads: 18
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3. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer : single center experienceJanja 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: 176; Downloads: 49
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6. Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experienceTanja Mesti, Maja Ebert Moltara, Marko Boc, Martina Reberšek, Janja Ocvirk, 2015, original scientific article Abstract: Treatment options of recurrent malignant gliomas are very limited and with a poor survival benefit. The results from phase II trials suggest that the combination of bevacizumab and irinotecan is beneficial. Patients and methods. The medical documentation of 19 adult patients with recurrent malignant gliomas was retrospectively reviewed. All patients received bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 or 125 mg/m2) every two weeks. Patient clinical characteristics, drug toxicities, response rate, progression free survival (PFS) and overall survival (OS) were evaluated. Results. Between August 2008 and November 2011, 19 patients with recurrent malignant gliomas (median age 44.7, male 73.7%, WHO performance status 0%2) were treated with bevacizumab/irinotecan regimen. Thirteen patients had glioblastoma, 5 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. With exception of one patient, all patients had initially a standard therapy with primary resection followed by postoperative chemoradiotherapy. Radiological response was confirmed after 3 months in 9 patients (1 complete response, 8 partial responses), seven patients had stable disease and three patients have progressed. The median PFS was 6.8 months (95% confidence interval [CI]: 5.3-8.3) with six-month PFS rate 52.6%. The median OS was 7.7 months (95% CI: 6.6-8.7), while six-month and twelve-month survival rates were 68.4% and 31.6%, respectively. There were 16 cases of hematopoietic toxicity grade (G) 1-2. Non-hematopoietic toxicity was present in 14 cases, all G1-2, except for one patient with proteinuria G3. No grade 4 toxicities, no thromboembolic event and no intracranial hemorrhage were observed. Conclusions. In recurrent malignant gliomas combination of bevacizumab and irinotecan might be an active regimen with acceptable toxicity.
Keywords: recurrent malignant glioma, systemic therapy, bevacizumab
Published in DiRROS: 17.04.2024; Views: 154; Downloads: 39
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7. Efficacy of first-line systemic treatment in correlation with BRAF V600E and different KRAS mutations in metastatic colorectal cancer : a single institution retrospective analysisMartina Reberšek, Marko Boc, Petra Škerl, Jernej Benedik, Zvezdana Hlebanja, Neva Volk, Srdjan Novaković, Janja Ocvirk, 2011, original scientific article Keywords: rak (medicina), debelo črevo, danka, zdravljenje
Published in DiRROS: 18.03.2024; Views: 136; Downloads: 49
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8. Cisplatin-induced non-convulsive posterior reversible encephalopathy syndrome in a 41-year-old woman with metastatic malignant melanomaJanja Ocvirk, Marko Boc, Martina Reberšek, Tanja Roš-Opaškar, 2009, original scientific article Abstract: Background. Cisplatin, a widely used antineoplastic agent usually induces peripheral neuropathy, but can rarely also complicate with encephalopathy, with or without seizures. Case report. We report a case of a young patient with metastatic malignant melanoma with signs and symptoms of cisplatin-induced non-convulsive posterior reversible encephalopaty syndrome. Within the days shortly after the first cycle of cisplatin based chemotherapy the patient suffered from nausea, vomitus, headache, severe pain at the site of sub-cutaneous metastases and confusion. She later experienced somnolence, cortical blindness and aphasia, but without epileptic seizures. Conclusions. Cisplatin is an effective chemotherapeutic drug but also very toxic one and physicians using it must also be aware of possible encephalopathy.
Published in DiRROS: 08.03.2024; Views: 194; Downloads: 49
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10. Electrochemotherapy with cisplatin of breast cancer tumor modules in a male patientMartina Reberšek, Tanja Čufer, Zvonimir Rudolf, Gregor Serša, 2000, original scientific article Abstract: Background. The metastases of breast cancer in a male patient were treated with electrochemotherapy by intratumoral injection of cisplatin. Electrochemotherapy is chemotherapy with the subsequent local application of electric pulses to the tumor nodules in order to increase drug delivery into the cells. Case report. Cutaneous metastases of breast cancer were treated with the intratumoral administration of cisplatin and by 8 electric pulses (1300 V/cm) applied a minute later to each cutaneous metastasis. The treatmentresulted in complete response of two electrochemotherapy treated cutaneous metastases and partial response of the third metastasis. In cutaneous metastases treated with intratumoral administartion of cisplatin without electric pulses, only partial response was obtained. Conclusion. This study confirms that electrochemotherapy with cisplatin is effective in the treatment of breast cancer metastases, too, as it was already proved for electrochemotherapy with bleomycin.
Published in DiRROS: 25.01.2024; Views: 219; Downloads: 50
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